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cholestyramine resin

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Description

Cholestyramine Resin: A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium Cl(-) anion. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID137699107
MeSH IDM0004278

Synonyms (6)

Synonym
cholestyramine
11041-12-6
cholestyramine resin
azane;2-methylbutane;trimethyl-[[4-(5-phenylhexan-3-yl)phenyl]methyl]azanium;chloride
MS-27791
AKOS040740752

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Adverse events were monitored."( Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years.
Clifton, P; Janus, ED; Nestel, PJ; Parfitt, A; Simons, J; Simons, LA, 1992
)
0.28
" Eight subjects allocated to pravastatin and seven allocated to resin withdrew (one and two subjects respectively because of drug-induced adverse events)."( Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years.
Clifton, P; Janus, ED; Nestel, PJ; Parfitt, A; Simons, J; Simons, LA, 1992
)
0.28
"Pravastatin was found to be a relatively effective, safe and well tolerated lipid-lowering drug."( Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years.
Clifton, P; Janus, ED; Nestel, PJ; Parfitt, A; Simons, J; Simons, LA, 1992
)
0.28
" It is concluded that simvastatin is a safe and efficient cholesterol-lowering drug for long-term therapy, both as a single drug and in combination with cholestyramine."( Long-term efficacy and safety of simvastatin alone and in combination therapy in treatment of hypercholesterolaemia.
Lundh, BL; Mölgaard, J; Olsson, AG; von Schenck, H, 1991
)
0.28
" The adverse effects of many of the principal drugs in this category are discussed."( A comparative review of the adverse effects of treatments for hyperlipidaemia.
Steiner, A; Vetter, W; Weisser, B,
)
0.13
" The most serious side-effect in our study was myolysis which occurred in two patients with a marked increase in creatine phosphokinase."( Efficacy and safety of simvastatin (alone or in association with cholestyramine). A 1-year study in 66 patients with type II hyperlipoproteinaemia.
Aubert, I; Bauduceau, B; Chanu, B; Dachet, C; Emmerich, J; Erlich, D; Gautier, D; Jacotot, B; Rouffy, J, 1990
)
0.28
" These results confirm that steatosis and necrosis are independent toxic effects of carbon tetrachloride."( Decreased acute hepatotoxicity of carbon tetrachloride and bromobenzene by cholestyramine in the rat.
Balabaud, C; Bedin, C; Bioulac, P; Despuyoos, L; Iron, A; Saric, J, 1981
)
0.26
" This study has shown that cerivastatin can be safely combined with either cholesytramine or probucol to provide a safe and highly effective hypolipidemic treatment regimen for patients with heterozygous familial hypercholesterolemia."( Clinical efficacy and safety of cerivastatin in the treatment of heterozygous familial hypercholesterolemia.
Kajinami, K; Koizumi, J; Mabuchi, H, 1998
)
0.3
" Ursodeoxycholic acid, but not cholestyramine was free of adverse effects."( Efficacy and safety of ursodeoxycholic acid versus cholestyramine in intrahepatic cholestasis of pregnancy.
Beuers, U; Kondrackiene, J; Kupcinskas, L, 2005
)
0.33
"Ursodeoxycholic acid is safe and more effective than cholestyramine in intrahepatic cholestasis of pregnancy."( Efficacy and safety of ursodeoxycholic acid versus cholestyramine in intrahepatic cholestasis of pregnancy.
Beuers, U; Kondrackiene, J; Kupcinskas, L, 2005
)
0.33
" A longer well-designed randomized controlled trial is needed to confirm the efficacy of bile acid binding agents and accurately assess adverse events."( The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus.
Bain, VG; Rowe, BH; Tandon, P; Vandermeer, B, 2007
)
0.34
" However, blocking FGFR4 or FGF19 has proven challenging due to its physiological role in suppressing bile acid synthesis which leads to increased toxic bile acid plasma levels upon FGFR4 inhibition."( Preclinical Development of U3-1784, a Novel FGFR4 Antibody Against Cancer, and Avoidance of Its On-target Toxicity.
Abraham, R; Agatsuma, T; Bange, J; Bartz, R; Chapman, RW; Fukuchi, K; Gruner, K; Hanai, M; Hanzawa, H; Häussinger, D; Hayashi, S; Imai, E; Kashimoto, Y; Kawaida, R; Komori, H; Lange, T; Martinez, A; Mayer, JA; Oda, Y; Ohtsuka, T; Redondo-Müller, M; Saito, S; Takahashi, M; Watanabe, I; Wirtz, P, 2019
)
0.51
"Non-alcoholic fatty liver disease (NAFLD) pathogenesis involves abnormal metabolism of cholesterol and hepatic accumulation of toxic free-cholesterol."( Rationale and design of a randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated phase 2a study to investigate the efficacy and safety of elobixibat in combination with cholestyramine for non-alcoholic fatty liver disease.
Honda, Y; Imajo, K; Iwaki, M; Kessoku, T; Kobayashi, T; Nakajima, A; Ogawa, Y; Ozaki, A; Saigusa, Y; Saito, S; Usuda, H; Wada, K; Yamamoto, K; Yamanaka, T; Yoneda, M, 2020
)
0.56
" This proof-of-concept study will determine whether the combination therapy of EXB and CTM is effective and safe for patients with NAFLD."( Rationale and design of a randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated phase 2a study to investigate the efficacy and safety of elobixibat in combination with cholestyramine for non-alcoholic fatty liver disease.
Honda, Y; Imajo, K; Iwaki, M; Kessoku, T; Kobayashi, T; Nakajima, A; Ogawa, Y; Ozaki, A; Saigusa, Y; Saito, S; Usuda, H; Wada, K; Yamamoto, K; Yamanaka, T; Yoneda, M, 2020
)
0.56

Pharmacokinetics

ExcerptReferenceRelevance
" Pharmacokinetic investigations incorporating such models are illustrated for two halogenated hydrocarbons that exhibit different patterns of disposition in the rat: 2,2',4,4',5,5'-hexachlorobiphenyl and Kepone."( Pharmacokinetics of halogenated hydrocarbons.
Bungay, PM; Dedrick, RL; Matthews, HB, 1979
)
0.26
" Pharmacokinetic factors responsible for inter- and intrasubject differences in the response to oral anticoagulant drugs."( [Pharmacokinetic aspects of overdosage and intoxication with oral anticoagulant drugs (author's transl)].
Jähnchen, E; Meinertz, T, 1977
)
0.26
" In 6 patients given cholestyramine together with clofibrate, there was no significant alteration in fasting plasma CPIB levels, 24-hour urinary and faecal excretion of CPIB or in the half-life and pool size of the drug."( Lack of effect of cholestyramine on the pharmacokinetics of clofibrate in man.
Ahrens, EH; Sedaghat, A, 1975
)
0.25
" The area under the serum concentration-time curve and maximum serum concentration of pravastatin showed dose-proportionality; time to maximum serum concentration and serum elimination half-life were independent of dose."( Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia.
Brescia, D; DeVault, AR; Ivashkiv, E; Pan, HY; Swites, BJ; Whigan, D; Willard, DA, 1990
)
0.28
" The mean terminal phase elimination half-life was reduced from 19."( The effect of cholestyramine on the pharmacokinetics of meloxicam, a new non-steroidal anti-inflammatory drug (NSAID), in man.
Busch, U; Heinzel, G; Narjes, H, 1995
)
0.29
"The effect of oral administration of the non-absorbable anion-exchange resins cholestyramine and colestipol on the systemic clearance and other pharmacokinetic parameters of intravenously administered ibuprofen (25 mg kg-1) was studied in rabbits."( The effect of colestipol and cholestyramine on the systemic clearance of intravenous ibuprofen in rabbits.
al-Angary, AA; al-Meshal, MA; el-Sayed, YM; Gouda, MW; Lutfi, KM, 1994
)
0.29
" Systemic exposure is limited because of extensive sequestration by the liver and/or first-pass metabolism, a plasma half-life of approximately 30 min, no circulating active metabolites, and no accumulation of drug during chronic dosing."( Pharmacokinetics of fluvastatin and specific drug interactions.
Hwang, DS; Jokubaitis, LA; Robinson, WT; Smith, HT; Troendle, AJ, 1993
)
0.29
" The decrease in mean AUC was now approximately 8-16% depending on the time of pretreatment (1-hour-interval: 16%, 5-hour-interval: 8%), and Cmax decreased by approximately 32%, irrespective of the time of pretreatment."( Influence of cholestyramine on the pharmacokinetics of cerivastatin.
Frey, R; Kuhlmann, J; Lücker, PW; Mück, W; Ritter, W; Wetzelsberger, N, 1997
)
0.3
" The estimated terminal half-life of ezetimibe and ezetimibe-glucuronide is approximately 22 hours."( Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions.
Alton, KB; Bergman, AJ; Johnson-Levonas, AO; Kosoglou, T; Paolini, JF; Statkevich, P, 2005
)
0.33
" The pharmacokinetic parameters of RGL and DMRGL were evaluated following oral or intravenous administration of RGL to rats at 10 mg kg-1 with and without pre-treatment (0."( Influence of cholestyramine on the pharmacokinetics of rosiglitazone and its metabolite, desmethylrosiglitazone, after oral and intravenous dosing of rosiglitazone: impact on oral bioavailability, absorption, and metabolic disposition in rats.
Mullangi, R; Muzeeb, S; Srinivas, NR; Venkatesh, P, 2006
)
0.33

Compound-Compound Interactions

ExcerptReferenceRelevance
"5 g/d) and large (up to 6 g/d) doses alone and in combination with cholestyramine."( Effects of neomycin alone and in combination with cholestyramine on serum cholesterol and fecal steroids in hypercholesterolemic subjects.
Miettinen, TA, 1979
)
0.26
"We have determined the effect of lovastatin alone or in combination with cholestyramine on lipoprotein (a) [Lp(a)] levels in 59 heterozygotes for familial hypercholesterolemia (FH) treated for 33."( Long-term effect of lovastatin alone and in combination with cholestyramine on lipoprotein (a) level in familial hypercholesterolemic subjects.
Berg, K; Foss, OP; Hjermann, I; Leren, P; Leren, TP, 1992
)
0.28
"The aim of the investigation was twofold: to study the effect of lovastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alone and in combination with other lipid lowering drugs in an open 48 week single centre study, and to study if lipid lowering drugs influence adherence to diet in adult patients with familial hypercholesterolemia."( [Familial hypercholesterolemia--intensive diet therapy combined with drug therapy].
Lund, H; Norseth, J; Ose, L; Stugaard, M; Wiig, I, 1992
)
0.28
"Pravastatin sodium (pravastatin), a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was administered alone (50 mg/kg) or in combination with cholestyramine, a bile acid sequestrant resin, at the level of 2% in the diet to homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits for 4 weeks."( Effects of pravastatin sodium alone and in combination with cholestyramine on hepatic, intestinal and adrenal low density lipoprotein receptors in homozygous Watanabe heritable hyperlipidemic rabbits.
Fukami, M; Fukushige, J; Itakura, H; Ito, T; Kuroda, M; Matsumoto, A; Nara, F; Shiomi, M; Tsujita, Y; Watanabe, Y, 1992
)
0.28
" The treated rabbits were given pravastatin sodium (50 mg/kg/day), an HMG-CoA reductase inhibitor, in combination with cholestyramine (2% in diet), a bile acid sequestrant, for 36 weeks."( Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low. Effect of pravastatin sodium in combination with cholestyramine.
Arai, M; Fukami, M; Fukushige, J; Ito, T; Kuroda, M; Shiomi, M; Tamura, A; Tsujita, Y; Watanabe, Y, 1990
)
0.28
"We have studied the effect of simvastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, alone and in combination with cholestyramine in 48 patients."( [HMG-CoA reductase inhibitors in familial hypercholesterolemia. Therapy with simvastatin alone and in combination with cholestyramine in low dosage; a report of 2 years experiences].
Burrichter, H; Geisel, J; Oette, K, 1990
)
0.28
"We have studied the effect of lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), alone and in combination with the bile acid sequestrant cholestyramine on lipid parameters in 30 heterozygous patients with familial hypercholesterolemia (FH) during a 20-week open trial."( Effects of lovastatin alone and in combination with cholestyramine on serum lipids and apolipoproteins in heterozygotes for familial hypercholesterolemia.
Berg, K; Foss, OP; Hjermann, I; Leren, P; Leren, TP; Viksmoen, L, 1988
)
0.27
"The effect of feeding 20 g beta-sitosterol/kg alone or in combination with cholestyramine (20 g/kg) during neonatal life of guinea-pigs on their subsequent response to a dietary cholesterol challenge in adult life was examined."( Effect of feeding beta-sitosterol alone or in combination with cholestyramine during early life on subsequent response to cholesterol challenge in adult life in guinea-pigs.
Gallon, LS; Hassan, AS; Subbiah, MT; Yunker, RL, 1982
)
0.26
"The effects of the two HMG CoA reductase inhibitors lovastatin and pravastatin in combination with 12-16 g cholestyramine on serum lipids were studied in 18 patients with severe primary hypercholesterolemia."( Long-term treatment (2 years) with the HMG CoA reductase inhibitors lovastatin or pravastatin in combination with cholestyramine in patients with severe primary hypercholesterolemia.
Jacob, BG; Richter, WO; Schwandt, P, 1993
)
0.29
" Patients completing the 52-week study participated in a further trial to assess whether the efficacy of fluvastatin (20-40 mg/day), either as monotherapy or in combination with cholestyramine (CME; 4-16 g/day), taken at least 4 hours prior to fluvastatin, is sustained for up to 3 years."( Long-term efficacy with fluvastatin as monotherapy and combined with cholestyramine (a 156-week multicenter study). French-Dutch Fluvastatin Study Group.
Banga, JD; Jacotot, B; Peters, TK; Waite, R, 1995
)
0.29
" Fibrates also have the potential to cause rhabdomyolysis, although generally only in combination with HMG-CoA reductase inhibitors, and are subject to binding by concomitantly administered bile acid sequestrants."( Antihyperlipidaemic agents. Drug interactions of clinical significance.
Farmer, JA; Gotto, AM, 1994
)
0.29
" In the subsequent, 6-week part of the study, the comparative efficacy, safety and tolerability of 20 mg fluvastatin, combined with cholestyramine (4 g, 8 g, or 16 g) were assessed."( Fluvastatin efficacy and tolerability in comparison and in combination with cholestyramine.
Bard, JM; Bodd, E; Borge, M; Eriksen, HM; Fruchart, JC; Hagen, E; Istad, H; Ose, L; Selvig, V; Wolf, MC, 1994
)
0.29
"Fluvastatin, a new synthetic inhibitor of HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, has been studied in several models to examine its effects when used in combination with other lipid-modifying agents such as derivatives of fibric acid (bezafibrate), resins (cholestyramine), and niacin."( Fluvastatin in combination with other lipid-lowering agents.
Jokubaitis, LA, 1996
)
0.29
" Judging from these results, SV was considered to interact with CT by the following procedure: SV underwent hydrolysis to SVH in aqueous solution, then CT activated the hydrolysis by binding the formed SVH, resulting in a significant reduction in concentration of SV."( Drug interaction between simvastatin and cholestyramine in vitro and in vivo.
Ichikawa, M; Matsuyama, K; Nakai, A; Nishikata, M, 1996
)
0.29
"This randomized, open-label study compared the cost efficiency of low-dose pravastatin combined with low-dose cholestyramine with high-dose pravastatin monotherapy in 59 patients with moderate hypercholesterolemia and coronary disease."( Pravastatin alone and in combination with low-dose cholestyramine in patients with primary hypercholesterolemia and coronary artery disease.
Ito, MK; Shabetai, R, 1997
)
0.3
"We assessed the short and long-term efficacy and safety of the lipid lowering drugs, nicotinic acid, and the HMG-CoA reductase inhibitor, lovastatin, in combination with cholestyramine in four renal transplant patients."( Effects of nicotinic acid and lovastatin in combination with cholestyramine in renal transplant patients.
Katyal, A; Lal, SM,
)
0.13
" Overall, ezetimibe has a favourable drug-drug interaction profile, as evidenced by the lack of clinically relevant interactions between ezetimibe and a variety of drugs commonly used in patients with hypercholesterolaemia."( Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions.
Alton, KB; Bergman, AJ; Johnson-Levonas, AO; Kosoglou, T; Paolini, JF; Statkevich, P, 2005
)
0.33
"Fluvastatin, a new synthetic inhibitor of HMGCoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, has been studied in several models to examine its effects when used in combination with other lipid-modifying agents such as derivatives of fibric acid (bezafibrate), resins (cholestyramine), and niacin."( Fluvastatin in combination with other lipid-lowering agents.
Jokubaitis, LA, 1994
)
0.29
" In this randomised, double-blind, placebo-controlled, parallel-group, phase IIa study, we aim to provide a proof-of-concept assessment by evaluating the efficacy and safety of EXB in combination with CTM in patients with NAFLD."( Rationale and design of a randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated phase 2a study to investigate the efficacy and safety of elobixibat in combination with cholestyramine for non-alcoholic fatty liver disease.
Honda, Y; Imajo, K; Iwaki, M; Kessoku, T; Kobayashi, T; Nakajima, A; Ogawa, Y; Ozaki, A; Saigusa, Y; Saito, S; Usuda, H; Wada, K; Yamamoto, K; Yamanaka, T; Yoneda, M, 2020
)
0.56

Bioavailability

ExcerptReferenceRelevance
" The rate of absorption decreased from the colon to the duodenum (colon greater than ileum greater than jejunum greater than duodenum)."( Intestinal oxalate absorption. I. Absorption in vitro.
Caspary, WF, 1977
)
0.26
" Thus, no influence of cholestyramine on the bioavailability of orally administered prednisolone could be demonstrated."( [Does cholestyramine impair the bioavailability of prednisolone?].
Audétat, V; Bircher, J; Paumgartner, G, 1977
)
0.26
" Ingestion of cholestyramine significantly reduced the bioavailability of PGA versus brewers yeast folate in rats."( Bioavailability of folate following ingestion of cholestyramine in the rat.
Hoppner, K; Lampi, B, 1991
)
0.28
" These data suggest a decrease in chloroquine bioavailability in the presence of cholestyramine."( [Interaction of cholestyramine and chloroquine].
Gendrel, D; Nardou, M; Richard-Lenoble, D; Verdier, F, 1990
)
0.28
" Among the drugs that can decrease digoxin bioavailability are cholestyramine, antacid gels, kaolin-pectate, certain antimicrobial drugs and cancer chemotherapeutic agents."( Pharmacokinetic interactions between digoxin and other drugs.
Marcus, FI, 1985
)
0.27
" It is concluded that cholestyramine does not significantly affect the bioavailability of a single dose of phenytoin."( Lack of effect of cholestyramine on phenytoin bioavailability.
Amione, C; Barzaghi, N; Frigo, GM; Lecchini, S; Monteleone, M; Perucca, E, 1988
)
0.27
" The bioavailability was reduced by colestipol 80%, by cholestyramine 95% and by activated charcoal 99."( Effects of resins and activated charcoal on the absorption of digoxin, carbamazepine and frusemide.
Hirvisalo, EL; Kivistö, K; Neuvonen, PJ, 1988
)
0.27
" In order to determine whether this abnormal metabolism also involved other sterols, a patient with sitosterolemia was fed a diet high in shellfish that contain significant quantities of noncholesterol sterols, some of which are less well absorbed than cholesterol in humans."( Abnormal metabolism of shellfish sterols in a patient with sitosterolemia and xanthomatosis.
Brewer, HB; Connor, WE; Gregg, RE; Lin, DS, 1986
)
0.27
" Bioavailability was determined from steady-state, 24-hour area under the serum concentration-time curve (AUC, ng X h/mL) and from 0- and 24-hour trough serum digoxin concentrations (ng/mL)."( A steady-state evaluation of the effects of propantheline bromide and cholestyramine on the bioavailability of digoxin when administered as tablets or capsules.
Brown, DD; Hull, JH; Long, RA; Schmid, J,
)
0.13
" Bile acid sequestrants are the most difficult of these agents to administer concomitantly, because their nonspecific binding results in decreased bioavailability of a number of other drugs, including thiazide diuretics, digitalis preparations, beta-blockers, coumarin anticoagulants, thyroid hormones, fibric acid derivatives and certain oral antihyperglycaemia agents."( Antihyperlipidaemic agents. Drug interactions of clinical significance.
Farmer, JA; Gotto, AM, 1994
)
0.29
" The in-vivo data suggest a reduction of diclofenac bioavailability when colestipol or cholestyramine is administered concomitantly."( The effects of cholestyramine and colestipol on the absorption of diclofenac in man.
al-Balla, SR; al-Meshal, MA; el-Sayed, YM; Gouda, MW, 1994
)
0.29
"The purpose of this study was to determine whether a concomitant single oral dose of one of the anion exchange resins colestipol hydrochloride (10 g) or cholestyramine (8 g) administered with ibuprofen (400 mg) would alter the bioavailability of this non-steroidal anti-inflammatory agent."( The effect of colestipol and cholestyramine on ibuprofen bioavailability in man.
al-Balla, SR; al-Meshal, MA; el-Sayed, YM; Gouda, MW, 1994
)
0.29
" Studies investigating the effect of food on fluvastatin pharmacokinetics have demonstrated marked reductions in the rate of bioavailability (Cmax) of 40% to 60%."( Pharmacokinetics of fluvastatin and specific drug interactions.
Hwang, DS; Jokubaitis, LA; Robinson, WT; Smith, HT; Troendle, AJ, 1993
)
0.29
" Also, the bioavailability relative to VPA alone was 86."( Effect of cholestyramine resin on single dose valproate pharmacokinetics.
Diskin, CJ; Malloy, MJ; Pennell, AT; Ravis, WR, 1996
)
0.29
" An illustration of the application of the program is presented to compare the bioavailability of ibuprofen when administered alone or followed by colestipol hydrochloride or by cholestyramine."( Design of crossover microcomputer program and application on drug bioequivalence data.
Abdullah, ME; El-Sayed, YM, 1995
)
0.29
" When both drugs were administered concomitantly in the morning under fasting conditions, a decrease in relative bioavailability by 21% could be observed, possibly due to irreversible adsorption of the statin to the resin."( Influence of cholestyramine on the pharmacokinetics of cerivastatin.
Frey, R; Kuhlmann, J; Lücker, PW; Mück, W; Ritter, W; Wetzelsberger, N, 1997
)
0.3
" Given the known hypocholesterolemic and antiatherosclerotic properties of some steroid glycosides, we synthesized a series of sterol derivatives by coupling some phytosterols known to interact with sterol absorption and also to be poorly absorbed to a cationic group."( Selection of cholesterol absorption inhibitors devoid of secondary intestinal effects.
Abou el Fadil, F; Boubia, B; Descroix-Vagne, M; Guffroy, C; Marquet, F; Pansu, D,
)
0.13
" In conclusion, CHA can reduce OTA concentrations in plasma as well as reducing nephrotoxicity, which may be attributed to a decrease of bioavailability and/or enterohepatic circulation of the toxin."( Dietary cholestyramine reduces ochratoxin A-induced nephrotoxicity in the rat by decreasing plasma levels and enhancing fecal excretion of the toxin.
Barriault, C; Bouchard, G; Frohlich, AA; Kerkadi, A; Marquardt, RR; Tuchweber, B; Yousef, IM, 1998
)
0.3
" Cholestyramine was tested in vivo to evaluate its capacity to reduce the bioavailability of fumonisins (FBs) in rats fed diet contaminated with toxigenic Fusarium verticillioides culture material."( In vitro and in vivo studies to assess the effectiveness of cholestyramine as a binding agent for fumonisins.
Avantaggiato, G; Chulze, S; Solfrizzo, M; Torres, A; Visconti, A, 2001
)
0.31
" Although coadministration with gemfibrozil and fenofibrate increased the bioavailability of ezetimibe, the clinical significance is thought to be minor considering the relatively flat dose-response curve of ezetimibe and the lack of dose-related increase in adverse events."( Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions.
Alton, KB; Bergman, AJ; Johnson-Levonas, AO; Kosoglou, T; Paolini, JF; Statkevich, P, 2005
)
0.33
" The oral bioavailability of RGL was reduced by 19."( Influence of cholestyramine on the pharmacokinetics of rosiglitazone and its metabolite, desmethylrosiglitazone, after oral and intravenous dosing of rosiglitazone: impact on oral bioavailability, absorption, and metabolic disposition in rats.
Mullangi, R; Muzeeb, S; Srinivas, NR; Venkatesh, P, 2006
)
0.33
"A clinical trial of (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphtyl) propanoic acid (DX-9065) revealed that its oral bioavailability was only 3% when it was administered as a conventional capsule formulation."( Improvement of low bioavailability of a novel factor Xa inhibitor through formulation of cationic additives in its oral dosage form.
Akashi, M; Fujii, Y; Kanamaru, T; Kikuchi, H; Nakagami, H; Sakuma, S; Yamashita, S, 2011
)
0.37

Dosage Studied

Male rats were dosed with toxin as described above. Animals were then dosed in the ileal loop with either cholestyramine resin (CTR, 50 mg/rat) or an equivalent vehicle. CHD incidence in men sustaining a fall of 25% in TOTAL-C or 35% in LDL-C levels was half that of men who remained at pretreatment levels.

ExcerptRelevanceReference
"Nine patients with familial hypercholesterolemia (type II hyperlipoproteinemia) and two normal volunteers were studied to ascertain the effectiveness of cholestyramine in lowering plasma cholesterol when a twice-a-day dosage regimen was compared with the same total dosage administered four times a day."( Cholestyramine: an effective, twice-daily dosage regimen.
Blum, CB; Havlik, RJ; Morganroth, J, 1976
)
0.26
" Nicotinic acid in the form of niceritrol had another type of dose-response in type II with doses from 3 to 6 g/day."( Cholestyramine, clofibrate and nicotinic acid as single or combined treatment of type IIa and IIb hyperlipoproteinaemia.
Carlson, LA; Olsson, AG; Orö, L; Rössner, S, 1975
)
0.25
" In the intermediate dosage range, both factors contributed to the decreased ratio."( Effect of 17alpha-ethinylestradiol on biliary excretion of bile acids.
Watanabe, H, 1975
)
0.25
"Cholestyramine in a mean dosage of 0-6 g/kg/day has been given to 18 children with familial hypercholesterolaemia for between one and two and a half years."( The effect of cholestyramine on intestinal absorption.
Lloyd, JK; West, RJ, 1975
)
0.25
" A test of the extent of the patients' understanding about the drugs they were taking showed that only 39% knew how the drug acted and the reasons for the chosen dosing schedule."( [Quality assurance in clinical trials. Problems related to patient information].
Eide, G; Ose, L; Pettersen, AG; Skjerdal, A; Wold, I, 1992
)
0.28
" This retrospective data analysis suggests that the combination of gemfibrozil and lovastatin may be safe in patients with normal renal function when the dosage of lovastatin is limited and when CK and ALT levels are monitored carefully."( A retrospective review of the use of lipid-lowering agents in combination, specifically, gemfibrozil and lovastatin.
McIntyre, TH; Shapiro, ML; Whitney, EJ; Wirebaugh, SR, 1992
)
0.28
"The aim of this study was to conduct dose-response studies of the effect of cholestyramine, alone or in combination with a test meal, on gallbladder emptying studied by ultrasonography in 31 healthy volunteers."( Opposite effects of cholestyramine and loxiglumide on gallbladder dynamics in humans.
Albano, O; Baldassarre, G; Belfiore, A; Palasciano, G; Portincasa, P, 1992
)
0.28
" A dose-response curve for each parameter measured was constructed using data from individual hamsters."( Cholesterol lowering and bile acid excretion in the hamster with cholestyramine treatment.
Benson, GM; Bond, B; Gee, A; Glen, A; Haynes, C; Jackson, B; Suckling, KE, 1991
)
0.28
"002), but only after the methotrexate dosage had been increased to 15 mg weekly."( [Methotrexate in the therapy of primary biliary cirrhosis].
Scheurlen, M; Weber, P; Wiedmann, KH, 1991
)
0.28
" Bezafibrate was well-tolerated, but gastro-intestinal side-effects were frequent during therapy with colestyramine, and 16 patients tolerated only a reduced dosage of this drug."( Efficacy of a combined bezafibrate retard-colestyramine treatment in patients with hypercholesterolemia.
Bergmann, S; Fischer, S; Fücker, K; Gehrisch, S; Hanefeld, M; Jaross, W; Lang, PD; Leonhardt, W, 1990
)
0.28
" These results demonstrate the effectiveness of such a well tolerated low dosage combination therapy."( Acipimox in combination with low dose cholestyramine for the treatment of type II hyperlipidaemia.
Bedford, DK; Gaw, A; Kilday, C; Lorimer, AR; Packard, CJ; Series, JJ; Shepherd, J, 1990
)
0.28
" Male rats were dosed with toxin as described above, and then animals were dosed in the ileal loop with either cholestyramine resin (CTR, 50 mg/rat) or an equivalent vehicle."( A model system for studying the bioavailability of intestinally administered microcystin-LR, a hepatotoxic peptide from the cyanobacterium Microcystis aeruginosa.
Beasley, VR; Carmichael, WW; Dahlem, AM; Hassan, AS; Swanson, SP, 1989
)
0.28
"The dose-response relationship of activated charcoal in reducing serum cholesterol was determined and the effects of charcoal and cholestyramine were compared in patients with hypercholesterolaemia."( Activated charcoal in the treatment of hypercholesterolaemia: dose-response relationships and comparison with cholestyramine.
Kuusisto, P; Manninen, V; Neuvonen, PJ; Vapaatalo, H, 1989
)
0.28
" In particular, modest lowering of dosage may preserve considerable LDL cholesterol lowering and virtually eliminate side effects."( Review of clinical studies of bile acid sequestrants for lowering plasma lipid levels.
LaRosa, J, 1989
)
0.28
" Simvastatin at the dosage of 10 mg appeared to be at least as efficient as 12 g of cholestyramine and generally better tolerated."( Comparison between low-dose simvastatin and cholestyramine in moderately severe hypercholesterolemia.
Deslypere, JP, 1989
)
0.28
" At the dosage regimens studied, superactivated charcoal and cholestyramine have comparable ability to lower plasma cholesterol concentrations."( Superactivated charcoal versus cholestyramine for cholesterol lowering: a randomized cross-over trial.
Kitt, TM; Park, GD; Spector, R, 1988
)
0.27
" During the attack phase of four weeks, three dosage regimens of MPC were used, 9 g, 12 g and 18 g for six patients in each group."( Differentiated dosage of microporous colestyramine and its double-blind comparison with a placebo in hypercholesterolaemic patients.
Bruno, M; Di Perri, T; Franchi, M, 1987
)
0.27
" Moreover, coronary heart disease incidence in men in sustaining a fall of 25% in total cholesterol, a typical response to the prescribed dosage (24 g/day) of cholestyramine resin, was half that of men who remained at pretreatment level."( The Lipid Research Clinics Coronary Primary Prevention Trial.
Rifkind, BM, 1986
)
0.27
"Ten healthy adult men participated in a study to evaluate appropriate dosing schedules of cholestyramine to minimize its effect on the absorption of hydrochlorothiazide (HCTZ)."( Influence of time intervals for cholestyramine dosing on the absorption of hydrochlorothiazide.
Hibbard, DM; Hunninghake, DB, 1986
)
0.27
" This study evaluated whether digoxin solution in capsules, a new dosage form with 90% to 100% bioavailability, would reduce such alterations, specifically those caused by cholestyramine and propantheline bromide."( A steady-state evaluation of the effects of propantheline bromide and cholestyramine on the bioavailability of digoxin when administered as tablets or capsules.
Brown, DD; Hull, JH; Long, RA; Schmid, J,
)
0.13
"Cholestyramine was administered to 15 men with type II hyperlipoproteinemia in a dosage of 8 gm twice daily."( Effect of time of administration of cholestyramine on plasma lipids and lipoproteins.
Hunninghake, DB; Peters, JR, 1985
)
0.27
" The ingested doses of lindane (mean dosage 120 mg/kg +/- 86 mg/kg) and benzene (mean dosage 366 mg/kg +/- 93 mg/kg) exceeded the toxic level."( Acute oral poisoning with lindane-solvent mixtures.
Donner, A; Haubenstock, A; Hruby, K; Jaeger, U; Pirich, K; Podczeck, A, 1984
)
0.27
" The low density lipoprotein (LDL) cholesterol and triglyceride concentrations decreased significantly (- 11%, - 21% and - 26% for LDL cholesterol on 4, 8 and 16 g, respectively) with a dose-response effect."( Diverging effects of cholestyramine on apolipoprotein B and lipoprotein Lp(a). A dose-response study of the effects of cholestyramine in hypercholesterolaemia.
Kostner, G; Lithell, H; Thomis, J; Vessby, B, 1982
)
0.26
"Addition of mineral oil to the diet (5%) of two rhesus monkeys that were dosed 29 wk earlier with 2,4,5,2',4',5'-hexabromobiphenyl (HBB) produced a 175% increase in fecal excretion of HBB."( Effect of mineral oil and/or cholestyramine in the diet on biliary and intestinal elimination of 2,4,5,2',4',5'-hexabromobiphenyl in the rhesus monkey.
Greim, HA; Rozman, KK; Rozman, TA; Williams, J, 1982
)
0.26
" Moreover, CHD incidence in men sustaining a fall of 25% in TOTAL-C or 35% in LDL-C levels, typical responses to the prescribed dosage (24 g/day) of cholestyramine resin, was half that of men who remained at pretreatment levels."( The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering.
, 1984
)
0.27
" Moreover, CHD incidence in men in whom a decrease of 25% in total cholesterol was sustained, a typical response to the prescribed dosage (24 g/day) of cholestyramine resin, was half that of men who remained at the pretreatment level."( Lipid Research Clinics Coronary Primary Prevention Trial: results and implications.
Rifkind, BM, 1984
)
0.27
" With a single drug regimen, compactin at a dosage of 15 mg/day produced a cholesterol reduction of 23% (70 mg/dl) in cases of combined hyperlipidemia, while twice the dosage (30 mg/day) was needed to produce a comparable effect with heterozygous familial hypercholesterolemia."( Combined drug therapy--cholestyramine and compactin--for familial hypercholesterolemia.
Matsuzawa, Y; Sudo, H; Yamamoto, A; Yamamura, T; Yokoyama, S, 1984
)
0.27
" The effects of cholestyramine rapidly disappeared when it was withdrawn from the diet, while the effects of gemfibrozil persisted after dosage was stopped."( Some comparative effects of gemfibrozil, clofibrate, bezafibrate, cholestyramine and compactin on sterol metabolism in rats.
Maxwell, RE; Nawrocki, JW; Uhlendorf, PD, 1983
)
0.27
" Patients were stratified by sex and extent of coronary disease as defined angiographically and were randomly allocated to a daily dosage of 24 g cholestyramine and diet (treatment group) or placebo and diet (control group)."( National Heart, Lung, and Blood Institute type II Coronary Intervention Study: design, methods, and baseline characteristics.
Aldrich, RF; Battaglini, JW; Brensike, JF; Detre, KM; Epstein, SE; Fisher, MR; Kelsey, SF; Levy, RI; Loh, IK; Moriarty, DJ; Myrianthopoulos, MB; Passamani, ER; Richardson, JM; Stone, NJ, 1982
)
0.26
" Similar dose-response results were seen with reductions in total cholesterol and the LDL-C: HDL-C ratio."( Efficacy of fluvastatin, a totally synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. FLUENT Study Group. Fluvastatin Long-Term Extension Trial.
Bergmann, SD; Haggerty, BJ; Winick, AG; Zavoral, JH, 1995
)
0.29
" Dose-response curves for serotonin-induced vasodilatation, an index of nitric oxide-dependent vasodilatation, showed a comparable and significant rightward shift after a medication-free period of 2 and 6 weeks compared with control subjects, indicating endothelial dysfunction, which was already maximum after 2 weeks."( Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication.
de Bruin, TW; Koomans, HA; Rabelink, TJ; Stroes, ES, 1995
)
0.29
" Preliminary studies in this model indicated that the uptake of 14C-cholesterol and its subsequent esterification 2 hr postoral dosing occurs primarily in the duodenal and jejunal segments of the small intestine and most of the radiolabeled cholesterol and cholesteryl ester in the plasma was associated with chylomicrons."( The effect of acyl CoA: cholesterol acyltransferase inhibition on the uptake, esterification and secretion of cholesterol by the hamster small intestine.
Burrier, RE; Davis, HR; Hoos, LM; McGregor, DG; Smith, AA; Zilli, DL, 1995
)
0.29
" A simultaneous intravenous/oral dosing regimen was used, with half of each group receiving treatment with neomycin and cholestyramine (neo/chol) to block the EHC of the drug."( Disposition of lorazepam in Gilbert's syndrome: effects of fasting, feeding, and enterohepatic circulation.
Chaudhary, A; Herman, RJ; Szakacs, CB, 1994
)
0.29
" For the present analysis, we identified 18 patients in the fluvastatin plus bezafibrate group (cohort 1) and 16 patients in the fluvastatin plus cholestyramine group (cohort 2) for whom complete dose-response data were available for the full 56-week duration of all 3 studies."( Fluvastatin in familial hypercholesterolemia: a cohort analysis of the response to combination treatment.
Leitersdorf, E; Muratti, EN; Peters, TK, 1994
)
0.29
" UDCA was administered at a dosage of 250 mg twice a day."( Different response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis according to severity of disease.
Chiaramonte, M; Floreani, A; Mazzetto, M; Naccarato, R; Plebani, M; Zappalà, F, 1994
)
0.29
" Drug interaction studies with fluvastatin and cholestyramine (CME) demonstrated a lower rate and extent of fluvastatin bioavailability; no impact on efficacy was demonstrated when CME was given 4 h before fluvastatin dosing in clinical trials."( Pharmacokinetics of fluvastatin and specific drug interactions.
Hwang, DS; Jokubaitis, LA; Robinson, WT; Smith, HT; Troendle, AJ, 1993
)
0.29
"After 8 weeks of therapy, pravastatin in a dosage of 20 mg twice daily reduced low-density lipoprotein cholesterol levels by 31%, whereas a dosage of 40 mg twice daily reduced low-density lipoprotein cholesterol levels by 38%."( Comparative efficacy and safety of pravastatin and cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter Study Group II.
, 1993
)
0.29
" After an 8-week interval in which a daily dosage of cholestyramine 8 g was added, from baseline, reductions of 26."( Fluvastatin in combination with other lipid-lowering agents.
Jokubaitis, LA, 1996
)
0.29
" Placing physiologic limits on values of GC* and Cl* suggests requisite selectivity properties of more potent bile acid sequestrants and dosing strategies to optimize current resin therapy."( Mathematical model and dimensional analysis of glycocholate binding to cholestyramine resin: implications for in vivo resin performance.
Amidon, GL; Polli, JE, 1995
)
0.29
" These two factors suggest that an increase in the dosage of the HMG-CoA reductase inhibitor may be appropriate."( Compliance with and efficacy of treatment with pravastatin and cholestyramine: a randomized study on lipid-lowering in primary care.
Eriksson, M; Hådell, K; Holme, I; Kjellström, T; Walldius, G, 1998
)
0.3
" In accordance with manufacturers' recommendations, maximum dosage was atorvastatin 80 mg daily or simvastatin 40 mg daily (+cholestyramine 4 g daily in 84% of cases)."( Comparison of atorvastatin alone versus simvastatin +/- cholestyramine in the management of severe primary hypercholesterolaemia (the six cities study).
Simons, LA, 1998
)
0.3
" The latter may generally be reduced by progressive and individual titration of the dosage of each drug and/or by following an appropriate diet."( [Drug clinics. How I treat various metabolic diseases treated by a drug intervention that targets the intestine].
Scheen, AJ, 1998
)
0.3
"The pharmacology, pharmacodynamics, clinical efficacy, drug interactions, adverse effects, and dosage and administration of colesevelam hydrochloride are reviewed."( Colesevelam hydrochloride.
Steinmetz, KL, 2002
)
0.31
" There are no clinically significant effects of age, sex or race on ezetimibe pharmacokinetics and no dosage adjustment is necessary in patients with mild hepatic impairment or mild-to-severe renal insufficiency."( Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions.
Alton, KB; Bergman, AJ; Johnson-Levonas, AO; Kosoglou, T; Paolini, JF; Statkevich, P, 2005
)
0.33
" Another objective of the study was to determine the effect of staggered oral CSA dosing at 1, 2 and 4 h after oral RGL administration at 10 mg kg-1."( Influence of cholestyramine on the pharmacokinetics of rosiglitazone and its metabolite, desmethylrosiglitazone, after oral and intravenous dosing of rosiglitazone: impact on oral bioavailability, absorption, and metabolic disposition in rats.
Mullangi, R; Muzeeb, S; Srinivas, NR; Venkatesh, P, 2006
)
0.33
"Intragastric conditions can affect the performance of solid dosage forms."( In vitro methods can forecast the effects of intragastric residence on dosage form performance.
Digenis, G; Kalantzi, L; Nicolaides, E; Page, R; Reppas, C, 2008
)
0.35
" After an 8-week interval in which a daily dosage of cholestyramine 8 g was added, from baseline, reductions of 26."( Fluvastatin in combination with other lipid-lowering agents.
Jokubaitis, LA, 1994
)
0.29
" Pooled data from 15 studies showed a dose-response relationship according to severity of malabsorption to treatment with a bile acid binder: response to colestyramine occurred in 96% of patients with <5% retention, 80% at <10% retention and 70% at <15% retention."( Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome.
A'Hern, R; Andreyev, HJ; Russell, D; Thomas, K; Walters, JR; Wedlake, L, 2009
)
0.35
" Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies."( Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide.
Aungst, A; Casady, L; Dixon, C; Maldonado, J; McCoy, B; Moreo, N; Robertson, D, 2017
)
0.46
" Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options."( Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide.
Aungst, A; Casady, L; Dixon, C; Maldonado, J; McCoy, B; Moreo, N; Robertson, D, 2017
)
0.46
" We used dose-response discrete-hazards models with inverse probability weighting to adjust for pre- and post-randomization covariates."( Adjusting for adherence in randomized trials when adherence is measured as a continuous variable: An application to the Lipid Research Clinics Coronary Primary Prevention Trial.
Hernán, MA; Madenci, AL; Murray, EJ; Wanis, KN, 2020
)
0.56
"2 percentage points with adjustment using inverse probability weights, depending on the dose-response model and inverse probability weight distribution used."( Adjusting for adherence in randomized trials when adherence is measured as a continuous variable: An application to the Lipid Research Clinics Coronary Primary Prevention Trial.
Hernán, MA; Madenci, AL; Murray, EJ; Wanis, KN, 2020
)
0.56
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (2,536)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901581 (62.34)18.7374
1990's536 (21.14)18.2507
2000's208 (8.20)29.6817
2010's164 (6.47)24.3611
2020's47 (1.85)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials342 (12.81%)5.53%
Reviews309 (11.58%)6.00%
Case Studies248 (9.29%)4.05%
Observational1 (0.04%)0.25%
Other1,769 (66.28%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (27)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
The Multicenter Atorvastatin Plaque Stabilization (MAPS) Study [NCT01053065]60 participants (Actual)InterventionalCompleted
A Randomized, Double-Blind, Placebo-Controlled Study Followed by an Open Label Treatment Period to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia [NCT03510884]Phase 3153 participants (Actual)Interventional2018-05-31Completed
An Open-label Pharmacokinetic and Tolerability Study of Teriflunomide Given as a Single 14 mg Dose in Subjects With Severe Renal Impairment, and in Matched Subjects With Normal Renal Function [NCT01239459]Phase 116 participants (Actual)Interventional2010-11-30Completed
Efficacy and Safety of Cholestyramine in the Management of Hyperphosphatemia in Adult Hemodialysis Patients [NCT05577507]Phase 480 participants (Anticipated)Interventional2023-03-30Enrolling by invitation
An 8-Week Open-Label, Sequential, Repeated Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia Followed by an Extension Phase [NCT02890992]Phase 242 participants (Actual)Interventional2016-09-15Completed
An Open-Label Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia [NCT03510715]Phase 318 participants (Actual)Interventional2018-08-31Completed
Low Doses of Cholestyramine in the Treatment of Hyperthyroidism [NCT00677469]45 participants (Actual)Interventional2007-07-31Completed
Pilot Trial of Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies [NCT05443425]Phase 118 participants (Anticipated)Interventional2023-06-16Recruiting
Exploratory Evaluation of the Effect of Cholestyramine on Serum Levels of Persistent Organic Pollutants in Obese Female Patients - OBESE (OBesity, cholEStyramine, womEn) [NCT05966727]20 participants (Anticipated)Interventional2023-12-31Not yet recruiting
Phase 2 Trial of Leflunomide in African-American and European-American Patients With High-Risk Smoldering Multiple Myeloma [NCT05014646]Phase 220 participants (Anticipated)Interventional2022-03-07Recruiting
An Open-label, Single-dose Study to Evaluate the Pharmacokinetic Profiles of 14 mg Teriflunomide Tablet in Healthy Chinese Subjects [NCT02046629]Phase 112 participants (Actual)Interventional2014-05-31Completed
[NCT00000463]Phase 30 participants Interventional1987-04-30Completed
[NCT00000594]Phase 30 participants Interventional1971-11-30Completed
[NCT02942602]58 participants (Actual)Interventional2014-04-03Completed
Master Protocol of Two Independent, Randomized, Double-blind, Phase 3 Studies Comparing Efficacy and Safety of Frexalimab (SAR441344) to Teriflunomide in Adult Participants With Relapsing Forms of Multiple Sclerosis [NCT06141473]Phase 31,400 participants (Anticipated)Interventional2023-12-13Recruiting
Exploratory Open Label Study to Investigate the Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Relapsing Forms of Multiple Sclerosis [NCT01863888]Phase 370 participants (Actual)Interventional2013-10-31Completed
A Phase 1 Study to Investigate the Effect of Cholestyramine on the Pharmacokinetics of LOXO-783 in Healthy Adults [NCT05894928]Phase 121 participants (Actual)Interventional2023-06-07Completed
A Randomized, Single-Blind, Single Research Site, Comparison of Colesevelam Hydrogen Chloride (HCl) Powder For Oral Suspension Versus Generic Cholestyramine Through Use of the Bile Acid Sequestrant Acceptability (BASA) Scale in Generally Healthy Subjects [NCT01122108]Phase 442 participants (Actual)Interventional2010-04-30Completed
[NCT00000461]Phase 20 participants Interventional1986-12-31Completed
[NCT00000488]Phase 30 participants Interventional1973-06-30Completed
A Phase I, Double-Blind Single and Multiple Ascending Dose Study to Assess Safety and Pharmacokinetics of A4250 as Monotherapy, and in Combination With Colonic Release Cholestyramine (A3384) or Commercially Available Cholestyramine (Questran™) in Healthy [NCT02963077]Phase 194 participants (Actual)Interventional2013-07-31Completed
A Clinical Study for Assessing the Effect of Change of Bile Acid Pool on the Pharmacodynamics and Safety of Metformin and Intestinal Microbiome Profiles in Healthy Volunteers [NCT04335526]Phase 115 participants (Actual)Interventional2020-05-01Completed
A Randomized Single Blind Placebo Controlled Single Research Site Bile Acid Sequestrant Acceptability (BASA) Scale Pilot Validation Study in Generally Healthy Subjects [NCT01062269]Phase 442 participants (Actual)Interventional2010-01-31Completed
A Multi-center, Open Label, Randomised Parallel- Group Study to Compare the Efficacy of Cholestyramine Plus Standard Treatment Versus Prednisolone Plus Standard Treatment Versus Standard Treatment Alone in Treatment of Overt Hyperthyroidism [NCT03303053]Phase 3135 participants (Anticipated)Interventional2017-05-11Recruiting
PRELIMINARY EVALUATION OF RETINAL EFFECTS OF PHARMACOLOLOGICAL LOWERING OF SERUM LEVES OF ADVANCED GLYCATION END-PRODUCTS (AGEs) IN TYPE 2 DIABETIC PATIENTS [NCT02249897]Phase 47 participants (Actual)Interventional2015-01-31Completed
A Phase IIa, Proof of Concept, Randomized, Double-Blind, Dose-Finding, Cross-Over Study of the Efficacy, Safety and Tolerability of a New Enteric-Coated Cholestyramine Capsule in Adult Short Bowel Syndrome Patients [NCT04046328]Phase 213 participants (Actual)Interventional2019-10-15Terminated(stopped due to Difficult recruitment)
Efficacy and Safety of Elobixibat in Combination With Cholestyramine for Patients With Nonalcoholic Fatty Liver Disease: a Single Center, Double-blind, Randomized, Placebo-Controlled, Phase 2a Trial. [NCT04235205]Phase 2102 participants (Actual)Interventional2020-01-29Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT01062269 (2) [back to overview]Weighted vs. Unweighted BASA Scale
NCT01062269 (2) [back to overview]Patient Acceptability of Orange-flavored Generic Questran (Cholestyramine) vs. Tang (a Commercial Powdered Orange Drink) Via 2 Versions of a Bile Acid Sequestrant Acceptability (BASA) Scale.
NCT01122108 (2) [back to overview]Patient Acceptability of Colesevelam HCl Powder for Oral Suspension vs. Generic Cholestyramine Via the Bile Acid Sequestrant Acceptability (BASA) Scale, Based Upon an Anticipated Equivalent Cholesterol Lowering Doses of Each Comparator Drug.
NCT01122108 (2) [back to overview]Weighted vs. Unweighted Composite BASA Scale Scores
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Fasting Triglyceride at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in HDL-C at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Lipoprotein(a) at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in Apolipoprotein A-1 at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4
NCT02890992 (20) [back to overview]Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in Fasting Triglyceride at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in Lipoprotein(a) at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8
NCT02890992 (20) [back to overview]Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8
NCT02890992 (20) [back to overview]Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8
NCT02890992 (20) [back to overview]Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Apolipoprotein A-1 at Week 8
NCT02890992 (20) [back to overview]Absolute Change From Baseline in Apolipoprotein B at Week 8
NCT03510715 (13) [back to overview]Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48
NCT03510715 (13) [back to overview]Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis
NCT03510715 (13) [back to overview]Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis
NCT03510715 (13) [back to overview]Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand
NCT03510884 (44) [back to overview]Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand
NCT03510884 (44) [back to overview]OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand
NCT03510884 (44) [back to overview]OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand
NCT03510884 (44) [back to overview]Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104
NCT03510884 (44) [back to overview]DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response
NCT03510884 (44) [back to overview]DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand
NCT03510884 (44) [back to overview]DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand
NCT04046328 (4) [back to overview]Change in the Weekly Frequency of Bowel Movements Measured Between Baseline and the Second Week of Treatment
NCT04046328 (4) [back to overview]Mean Daily Dose of Loperamide in mg, if Used, During the Second Week of Treatment
NCT04046328 (4) [back to overview]Mean Daily Stool Form Score According to the BSFS (Bristol Stool Form Scale), Measured During the Second Week of Treatment
NCT04046328 (4) [back to overview]Total Number of Bowel Movements for the Whole 2-week Treatment Period

Weighted vs. Unweighted BASA Scale

The total aggregate scores for the complete BASA scale were calculated for Cholestyramine 4g, Cholestyramine 12g, and Tang. The total best possible score was 20 and the total worst possible score was 4. A weighted aggregate BASA scale score was also calculated for the Cholestyramine 4g, Cholestyramine 12g, and Tang. The best possible weighted score was 60 and the worst possible weighted score was 4. (NCT01062269)
Timeframe: 1 Day

,,
InterventionUnits on Scale (Median)
Total BASA ScoreWeighted BASA Score
Cholestyramine 12 Grams9.422.6
Cholestyramine 4 Grams10.324.8
Tang16.741.3

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Patient Acceptability of Orange-flavored Generic Questran (Cholestyramine) vs. Tang (a Commercial Powdered Orange Drink) Via 2 Versions of a Bile Acid Sequestrant Acceptability (BASA) Scale.

The Bile Acid Sequestrant Acceptability Scale has 4 scoring categories: taste, texture, appearance and mixability. Participants rank each category separately. The best possible score for each category is 5 and the worst possible score is 1. (NCT01062269)
Timeframe: 1 Day

,,
InterventionUnits on Scale (Mean)
Taste ScoreTexture ScoreAppearance ScoreMixability Score
Cholestyramine 12 Grams2.52.02.82.1
Cholestyramine 4 Grams2.72.42.82.5
Tang4.24.34.14.1

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Patient Acceptability of Colesevelam HCl Powder for Oral Suspension vs. Generic Cholestyramine Via the Bile Acid Sequestrant Acceptability (BASA) Scale, Based Upon an Anticipated Equivalent Cholesterol Lowering Doses of Each Comparator Drug.

The bile acid sequestrant acceptability (BASA) scale has 4 scoring categories: taste, texture, appearance, and mixability. Participants rank each category separately. The best possible score for each category is 5, and the worst possible score for each category is 1. (NCT01122108)
Timeframe: 1 Day

,
InterventionUnits on BASA Scale (Mean)
Taste ScoreTexture ScoreAppearance ScoreMixability Score
Cholestyramine (12g)2.672.363.482.6
Colesevelam HCl (3.75g)3.262.622.692.74

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Weighted vs. Unweighted Composite BASA Scale Scores

Aggregate scores were calculated for both the unweighted and weighted BASA scale scores for both Colesevlam HCL (3.75G) and Cholestyramine (12g). The best possible total BASA score is 20 and the worst possible total BASA score is 4. For the weighted version of the scale, the best possible total score is 60 and the worst possible total score is 4. (NCT01122108)
Timeframe: 1 Day

,
InterventionUnits on a BASA Scale (Mean)
Total BASA ScoreTotal Weighted BASA Score
Cholestyramine (12g)11.1026.05
Colesevelam HCl (3.75g)11.3127.29

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Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8

Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionmilligram per deciliter (mg/dL) (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-83.7
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-27.6
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-55.5
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-88.3
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-32.4
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg0.1
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-55.9
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-104.3

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Absolute Change From Baseline in Fasting Triglyceride at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionmmol/L (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-0.121
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-0.076
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg0.168
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg0.111
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg0.117
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-0.045
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-0.402
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-0.107

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Absolute Change From Baseline in HDL-C at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionmg/dL (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg5.9
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg7.7
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg5.5
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg4.9
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg2.4
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg5.9
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg2.2
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg1.2

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Absolute Change From Baseline in Lipoprotein(a) at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. (NCT02890992)
Timeframe: Baseline, Week 8

Interventiongram/Liter (g/L) (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg0.003
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-0.021
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg0.007
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-0.025
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg0.023
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-0.031
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-0.002
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-0.120

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Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionmg/dL (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-86.1
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-28.7
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-62.7
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-88.5
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-29.5
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-0.6
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-63.1
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-106.4

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Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionratio (Apo B/Apo A-1) (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-0.363
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-0.262
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-0.370
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-0.402
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-0.190
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-0.086
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-0.282
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-0.473

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Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline value and post-baseline values in at least one of the analysis windows used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-38.4
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-9.7
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-36.4
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-40.1
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-12.6
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-0.9
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-27.2
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-51.4

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Percent Change From Baseline in Apolipoprotein A-1 at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg4.4
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg14.8
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg10.7
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg1.8
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg8.9
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg7.4
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg5.8
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg7.2

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Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4

Adjusted LS means and standard error at Week 12 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. (NCT02890992)
Timeframe: Baseline, Week 12

Interventionpercent change (Least Squares Mean)
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-29.7
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-49.2

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Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8

Percent change in calculated LDL-C was defined as 100*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period & within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 & 2) or +35 days (for Cohorts 3 & 4). Adjusted Least-squares (LS) mean & standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W [<50 kg], 40 mg Q2W [<50 kg], 50 mg Q2W [>=50 kg], 75 mg Q2W [>=50 kg], 75 mg Q4W [<50 kg],150 mg Q4W [>=50 kg], 150 mg Q4W [<50 kg] and 300 mg Q4W ([>=50 kg] dose), time point & dose/dose regimen-by-time point interaction. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-41.1
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-7.9
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-40.6
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-49.8
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-17.5
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg4.0
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-31.9
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-59.8

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Percent Change From Baseline in Fasting Triglyceride at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-0.4
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-4.0
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-7.4
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg14.5
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg19.3
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-3.1
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-32.1
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-7.1

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Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg9.7
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg16.5
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg14.7
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg10.6
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg5.2
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg13.8
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg4.5
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg2.8

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Percent Change From Baseline in Lipoprotein(a) at Week 8

Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg4.5
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-26.9
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg1.5
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-25.2
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg2.2
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-7.7
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg0.1
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-7.7

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Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-39.6
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-7.1
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-39.7
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-43.9
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-14.4
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg3.2
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-31.5
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-54.6

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Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionpercent change (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-29.0
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-4.1
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-28.6
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-34.2
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-10.7
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg5.2
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-24.0
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-41.8

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Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8

Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. (NCT02890992)
Timeframe: At Week 8

Interventionpercentage of participants (Number)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg0.0
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg0.0
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg93.4
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg65.7
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg16.7
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg20.0
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg66.7
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg80.0

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Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8

Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. (NCT02890992)
Timeframe: At Week 8

Interventionpercentage of participants (Number)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg100.0
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg33.3
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg97.6
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg83.0
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg33.3
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg20.0
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg66.7
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg80.0

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Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionmg/dL (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-80.1
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-20.8
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-57.1
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-84.4
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-27.2
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg5.3
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-60.7
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-105.1

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Absolute Change From Baseline in Apolipoprotein A-1 at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionmg/dL (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg4.0
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg17.7
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg11.3
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-0.4
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg10.5
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg8.0
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg7.5
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg11.0

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Absolute Change From Baseline in Apolipoprotein B at Week 8

Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. (NCT02890992)
Timeframe: Baseline, Week 8

Interventionmg/dL (Least Squares Mean)
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg-51.7
Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg-18.5
Cohort 2 - Alirocumab 40 mg Q2W: <50 kg-35.3
Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg-53.4
Cohort 3 - Alirocumab 75 mg Q4W: <50 kg-15.3
Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg-5.4
Cohort 4 - Alirocumab 150 mg Q4W: <50 kg-34.2
Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg-63.5

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Number of Participants With Tanner Staging at Baseline, Weeks 12, 24 and 48

Tanner stage defines physical measurements of development in children and adolescent based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males), and classified in 3 categories as: Prepubescent (defined as a person just before start of the development of adult sexual characteristics), Pubescent (defined as a person at or approaching the age of puberty), Postpubescent (sexually mature or a person who has completed puberty). (NCT03510715)
Timeframe: Baseline, Weeks 12, 24 and 48

,
InterventionParticipants (Count of Participants)
Baseline: PrepubescentBaseline: PubescentBaseline: Post-pubescentWeek 12: PrepubescentWeek 12: PubescentWeek 12: Post-pubescentWeek 24: PrepubescentWeek 24: PubescentWeek 24: Post-pubescentWeek 48: PrepubescentWeek 48: PubescentWeek 48: Post-pubescent
Alirocumab 150 mg Q2W090081081072
Alirocumab 75 mg Q2W/up to 150 mg Q2W360360260170

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Percent Change From Baseline in Apolipoprotein (Apo) B at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercent change (Least Squares Mean)
Week 12Week 24Week 48
Alirocumab-4.2-11.80.9

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Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercent change (Least Squares Mean)
Week 12Week 24Week 48
Alirocumab11.314.611.3

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Percent Change From Baseline in Fasting Triglycerides (TG) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercent change (Mean)
Week 12Week 24Week 48
Alirocumab2.85.210.0

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Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercent change (Least Squares Mean)
Week 12Week 24Week 48
Alirocumab13.08.910.1

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Percent Change From Baseline in Lipoprotein a (Lp) (a) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data from Week 4 to Week 48 regardless of status on-or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercent change (Mean)
Week 12Week 24Week 48
Alirocumab7.4-5.2-6.4

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Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Weeks 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 24 and 48

Interventionpercent change (Least Squares Mean)
Week 24Week 48
Alirocumab-10.14.2

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Percent Change From Baseline in Total Cholesterol (Total-C) at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Weeks 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercent change (Least Squares Mean)
Week 12Week 24Week 48
Alirocumab-1.9-6.35.5

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Percentage of Participants Reporting >=15 Percent (%) Reduction in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted Percentage were obtained from a multiple imputation approach for handling of missing data including all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercentage of participants (Number)
Week 12Week 24Week 48
Alirocumab50.050.039.0

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Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12: Intent-to-Treat (ITT) Analysis

Adjusted least square (LS) means and standard errors were obtained from the mixed model analysis with repeated measures (MMRM) to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). (NCT03510715)
Timeframe: Baseline to Week 12

Interventionpercent change (Least Squares Mean)
Alirocumab-4.1

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Percent Change From Baseline in Low-Density Lipoprotein Cholesterol at Week 12: On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline on-treatment data from Week 4 to Week 48 (on-treatment Analysis). (NCT03510715)
Timeframe: Baseline to Week 12

Interventionpercent change (Least Squares Mean)
Alirocumab-4.1

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Absolute Change From Baseline in LDL-C Level at Weeks 12, 24 and 48: ITT Analysis/On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionmg/dL (Least Squares Mean)
Week 12Week 24Week 48
Alirocumab-33.4-43.0-15.0

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Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Weeks 12, 24 and 48 - ITT Analysis/On-treatment Analysis

Adjusted LS means and standard errors were obtained from the MMRM model to account for missing data using all available post-baseline data from Week 4 to Week 48 regardless of status on- or off-treatment used in the model (ITT analysis). Although separate analyses of all available data (ITT analysis) and only data collected within a defined time window (On-treatment analysis) were planned, if all values used in the ITT approach were within the on-treatment time window, the on-treatment analysis would be identical to the ITT analysis, thus the results would be identical and a single outcome measure presenting the results for both types of analysis would be provided. (NCT03510715)
Timeframe: Baseline to Weeks 12, 24 and 48

Interventionpercent change (Least Squares Mean)
Week 12Week 24Week 48
Alirocumab-3.9-9.25.7

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DB Period: Percentage of Participants Achieved at Least 30% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand

Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. (NCT03510884)
Timeframe: At Weeks 12 and 24

,,,
Interventionpercentage of participants (Number)
Week 12Week 24
DB Period: Alirocumab Q2W65.866.7
DB Period: Alirocumab Q4W70.872.5
DB Period: Placebo Q2W0.84.0
DB Period: Placebo Q4W4.218.5

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DB Period: Percentage of Participants Who Achieved at Least 30 Percent (%) Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand

Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model. (NCT03510884)
Timeframe: At Weeks 12 and 24

,,,
Interventionpercentage of participants (Number)
Week12Week 24
DB Period: Alirocumab Q2W65.866.7
DB Period: Alirocumab Q4W70.872.5
DB Period: Placebo Q2W0.84.0
DB Period: Placebo Q4W4.218.5

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DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: ITT Estimand

Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model. (NCT03510884)
Timeframe: At Weeks 12 and 24

,,,
Interventionpercentage of participants (Number)
Week 12Week 24
DB Period: Alirocumab Q2W25.221.6
DB Period: Alirocumab Q4W31.932.4
DB Period: Placebo Q2W0.00.0
DB Period: Placebo Q4W0.19.1

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DB Period: Percentage of Participants Who Achieved at Least 50% Reduction in Low Density Lipoprotein Cholesterol Level From Baseline at Weeks 12 and 24: On-treatment Estimand

Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. (NCT03510884)
Timeframe: At Weeks 12 and 24

,,,
Interventionpercentage of participants (Number)
Week 12Week 24
DB Period: Alirocumab Q2W25.221.6
DB Period: Alirocumab Q4W31.932.4
DB Period: Placebo Q2W0.00.0
DB Period: Placebo Q4W0.19.1

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DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 110 mg/dL (2.84 mmol/L) at Weeks 12 and 24: On-treatment Estimand

Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. (NCT03510884)
Timeframe: Weeks 12 and 24

,,,
Interventionpercentage of participants (Number)
Week 12Week 24
DB Period: Alirocumab Q2W61.757.2
DB Period: Alirocumab Q4W57.067.2
DB Period: Placebo Q2W0.14.0
DB Period: Placebo Q4W4.39.0

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DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 24: Intent-to-treat (ITT) Estimand

Adjusted least square (LS) means and standard errors (SE) were obtained from mixed-effect model with repeated measures (MMRM) model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W9.7
DB Period: Alirocumab Q2W-33.6
DB Period: Placebo Q4W-4.4
DB Period: Alirocumab Q4W-38.2

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Number of Participants With Tanner Staging at Baseline and Weeks 24, 68 and 104

Tanner stage defines physical measurements of development in children and adolescent based on external primary and secondary sex characteristics. Participants were evaluated for pubic hair distribution, breast development (only females) and genital development (only males) and classified in 3 categories as: Prepubescent (defined as a person just before start of the development of adult sexual characteristics), Pubescent (defined as a person at or approaching the age of puberty), Postpubescent (sexually mature or a person who has completed puberty). (NCT03510884)
Timeframe: Baseline, Weeks 24, 68 and 104

,,,
InterventionParticipants (Count of Participants)
Baseline: Boys - PrepubescentBaseline: Boys - PubescentBaseline: Boys - PostpubescentBaseline: Girls - PrepubescentBaseline: Girls - PubescentBaseline: Girls - PostpubescentWeek 24: Boys - PrepubescentWeek 24: Boys - PubescentWeek 24: Boys - PostpubescentWeek 24: Girls - PrepubescentWeek 24: Girls - PubescentWeek 24: Girls - PostpubescentWeek 68: Boys - PrepubescentWeek 68: Boys - PubescentWeek 68: Boys - PostpubescentWeek 68: Girls - PrepubescentWeek 68: Girls - PubescentWeek 68: Girls - PostpubescentWeek 104: Boys - PrepubescentWeek 104: Boys - PubescentWeek 104: Boys - PostpubescentWeek 104: Girls - PrepubescentWeek 104: Girls - PubescentWeek 104: Girls - Postpubescent
Alirocumab Q2W41324161031134159196314918601011
Alirocumab Q4W01447131401252169096116908711711
Placebo/Alirocumab Q2W11331610134152074061067042
Placebo/Alirocumab Q4W543186173165153155152155

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DB Period: Percent Change From Baseline in Apolipoprotein A1 (Apo A1) at Week 24: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W-0.1
DB Period: Alirocumab Q2W1.0
DB Period: Placebo Q4W-4.5
DB Period: Alirocumab Q4W4.4

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DB Period: Percent Change From Baseline in Apolipoprotein A1 at Week 12: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W-0.1
DB Period: Alirocumab Q2W-1.7
DB Period: Placebo Q4W-0.7
DB Period: Alirocumab Q4W5.0

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DB Period: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 24: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W10.4
DB Period: Alirocumab Q2W-27.4
DB Period: Placebo Q4W-3.6
DB Period: Alirocumab Q4W-34.3

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DB Period: Percent Change From Baseline in Apolipoprotein B at Week 12: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W8.9
DB Period: Alirocumab Q2W-30.0
DB Period: Placebo Q4W1.1
DB Period: Alirocumab Q4W-31.7

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DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12: ITT Estimand

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 12. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Mean)
DB Period: Placebo Q2W6.5
DB Period: Alirocumab Q2W-2.2
DB Period: Placebo Q4W7.8
Db Period: Alirocumab Q4W-0.3

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DB Period: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 24: ITT Estimand

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Mean)
DB Period: Placebo Q2W7.7
DB Period: Alirocumab Q2W11.9
DB Period: Placebo Q4W12.2
DB Period: Alirocumab Q4W-6.8

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DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 24: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W-0.8
DB Period: Alirocumab Q2W5.6
DB Period: Placebo Q4W-1.1
DB Period: Alirocumab Q4W3.4

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DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol at Week 12: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W-2.2
DB Period: Alirocumab Q2W3.5
DB Period: Placebo Q4W-3.5
DB Period: Alirocumab Q4W4.0

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DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol < 130 mg/dL (3.37 mmol/L) at Weeks 12 and 24: On-treatment Estimand

Adjusted percentages at Weeks 12 and 24 were obtained from multiple imputation approach for handling of missing data followed by logistic regression model. All available post-baseline on-treatment data up to Week 12 and Week 24 were included in the imputation model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. (NCT03510884)
Timeframe: Weeks 12 and 24

,,,
Interventionpercentage of participants (Number)
Week 12Week 24
DB Period: Alirocumab Q2W70.673.3
DB Period: Alirocumab Q4W72.676.3
DB Period: Placebo Q2W16.48.0
Db Period: Placebo Q4W12.922.2

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DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 12: ITT Estimand

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 12. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Mean)
DB Period: Placebo Q2W-7.1
DB Period: Alirocumab Q2W-12.7
DB Period: Placebo Q4W-2.5
DB Period: Alirocumab Q4W-16.0

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DB Period: Percent Change From Baseline in Lipoprotein (a) at Week 24: ITT Estimand

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline data up to Week 24. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Mean)
DB Period: Placebo Q2W0.5
DB Period: Alirocumab Q2W-14.7
DB Period: Placebo Q4W2.5
DB Period: Alirocumab Q4W-22.4

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DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 12: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W10.7
DB Period: Alirocumab Q2W-34.8
DB Period: Placebo Q4W2.3
DB Period: Alirocumab Q4W-39.2

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DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W9.7
DB Period: Alirocumab Q2W-31.0
DB Period: Placebo Q4W-3.7
DB Period: Alirocumab Q4W-35.6

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DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Week 12: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W9.8
DB Period: Alirocumab Q2W-33.0
DB Period: Placebo Q4W2.8
DB Period: Alirocumab Q4W-34.7

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DB Period: Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 24

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W7.4
DB Period: Alirocumab Q2W-23.4
DB Period: Placebo Q4W-4.4
DB Period: Alirocumab Q4W-27.7

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DB Period: Percent Change From Baseline in Total Cholesterol at Week 12: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model including all available post-baseline data. All post-baseline data available up to Week 12 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Week 12

Interventionpercent change (Least Squares Mean)
DB Period: Placebo Q2W7.5
DB Period: Alirocumab Q2W-25.3
DB Period: Placebo Q4W0.9
DB Period: Alirocumab Q4W-27.0

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DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 12: ITT Estimand

Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data for Q4W. All available post-baseline data up to Week 12 were included in the imputation model. For Q2W, adjusted percentages at Week 12 were obtained from last observation carried forward approach (LOCF) to handle missing on-treatment LDL-C values as well as missing post-treatment LDL-C values in participants who discontinued treatment due to the coronavirus disease-2019 pandemic. Other post-treatment missing values were considered as failure. (NCT03510884)
Timeframe: At Week 12

Interventionpercentage of participants (Number)
DB Period: Placebo Q2W0.0
DB Period: Alirocumab Q2W61.2
DB Period: Placebo Q4W4.3
DB Period: Alirocumab Q4W57.0

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DB Period: Percentage of Participants Achieving Low Density Lipoprotein Cholesterol <110 mg/dL (2.84 mmol/L) at Week 24: ITT Estimand

Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 24 were included in the imputation model. (NCT03510884)
Timeframe: At Week 24

Interventionpercentage of participants (Number)
DB Period: Placebo Q2W4.0
DB Period: Alirocumab Q2W57.2
DB Period: Placebo Q4W9.0
DB Period: Alirocumab Q4W67.2

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DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level <130 mg/dL (3.37 mmol/L) at Week 12: ITT Estimand

Adjusted percentages at Week 12 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 12 were included in the imputation model. (NCT03510884)
Timeframe: At Week 12

Interventionpercentage of participants (Number)
DB Period: Placebo Q2W16.4
DB Period: Alirocumab Q2W70.6
DB Period: Placebo Q4W12.9
DB Period: Alirocumab Q4W72.6

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DB Period: Percentage of Participants Who Achieved Low Density Lipoprotein Cholesterol Level Lower Than (<) 130 mg/dL (3.37 mmol/L) at Week 24: ITT Estimand

Adjusted percentages at Week 24 were obtained from multiple imputation approach for handling of missing data. All available post-baseline data up to Week 24 were included in the imputation model. (NCT03510884)
Timeframe: At Week 24

Interventionpercentage of participants (Number)
DB Period: Placebo Q2W8.0
DB Period: Alirocumab Q2W73.3
DB Period: Placebo Q4W22.2
DB Period: Alirocumab Q4W76.3

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OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: ITT Estimand

Percent Change in LDL-C from Baseline to Week 104 was reported in this outcome measure. (NCT03510884)
Timeframe: Baseline, Week 104

Interventionpercent change (Least Squares Mean)
OL Period: Placebo/Alirocumab Q2W-23.3
OL Period: Alirocumab Q2W-22.2
OL Period: Placebo/Alirocumab Q4W-27.1
OL Period: Alirocumab Q4W-23.7

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OL Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Week 104: On-treatment Estimand

Percent Change in LDL-C from Baseline to Week 104 was reported in this outcome measure. (NCT03510884)
Timeframe: Baseline, Week 104

Interventionpercent change (Least Squares Mean)
OL Period: Placebo/Alirocumab Q2W-22.8
OL Period: Alirocumab Q2W-25.8
OL Period: Placebo/Alirocumab Q4W-27.6
OL Period: Alirocumab Q4W-23.4

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Change From Baseline in Cogstate Battery Test - Overall Composite Score at Weeks 24, 68 and 104

Cogstate battery test (cognitive testing system) consisted of detection test (DET), identification test (IDN), one card learning test (OCL) and Groton maze learning test (GML) to assess processing speed, attention, visual learning and executive functioning, respectively. For each test, Z-scores were computed based on participant's age at Baseline and Weeks 24, 68 and 104. Composite score: calculated as mean of Z-scores equally weighted, provided that at least 3 of 4 tests were available and if all of these domains were covered as: attention, through either DET or IDN, visual learning, through OCL and executive function, through GML. There is not minimum/maximum since values were reported as z-score but z-score of 0 means result equals to mean with negative numbers indicating values lower than mean and positive values higher. Positive change in z-score = an improvement in cognition, i.e., a better outcome; and negative change in z-score = worsening in cognition, i.e., a worse outcome. (NCT03510884)
Timeframe: Baseline, Weeks 24, 68 and 104

,,,
InterventionZ-score (Mean)
Week 24Week 68Week 104
Alirocumab Q2W-0.313-0.334-0.439
Alirocumab Q4W-0.136-0.263-0.638
Placebo/Alirocumab Q2W-0.403-0.421-0.601
Placebo/Alirocumab Q4W-0.218-0.272-0.393

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DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 12 and Week 24 were used and missing data were accounted for by the MMRM model. MMRM model was run on participants with a Baseline value and a post-baseline value for at least one timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12, and 24

,,,
Interventionratio (Apo B/Apo A-1) (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-0.2-0.2
DB Period: Alirocumab Q4W-0.3-0.3
DB Period: Placebo Q2W0.10.1
DB Period: Placebo Q4W0.00.0

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DB Period: Absolute Change From Baseline in Apo B/Apo A-1 Ratio at Weeks 12 and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12, and 24

,,,
Interventionratio (Apo B/Apo A-1) (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-0.2-0.2
DB Period: Alirocumab Q4W-0.3-0.3
DB Period: Placebo Q2W0.10.1
DB Period: Placebo Q4W0.00.0

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DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response

Anti-drug (alirocumab) antibodies samples were analyzed using a validated non-quantitative, titer-based bridging immunoassay. Number of participants with positive ADA during 24-week treatment period is reported. Treatment-emergent positive ADA response was defined as 1) participants with no ADA positive response at baseline but with any positive response in the post-baseline period or 2) participants with a positive ADA response at baseline and at least a 4- fold increase in titer in the post-baseline period. A persistent positive response was defined as a TE ADA positive response detected in at least 2 consecutive post-baseline samples separated by at least a 12-week period. Persistent positive response was only analyzed for participants with positive TE ADA response. (NCT03510884)
Timeframe: Up to 24 weeks

,,
InterventionParticipants (Count of Participants)
TE ADA positive response
DB Period: Alirocumab Q4W0
DB Period: Placebo Q2W0
DB Period: Placebo Q4W0

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DB Period: Number of Participants With Treatment-Emergent (TE) Positive Anti-Alirocumab Antibodies (ADA) Response

Anti-drug (alirocumab) antibodies samples were analyzed using a validated non-quantitative, titer-based bridging immunoassay. Number of participants with positive ADA during 24-week treatment period is reported. Treatment-emergent positive ADA response was defined as 1) participants with no ADA positive response at baseline but with any positive response in the post-baseline period or 2) participants with a positive ADA response at baseline and at least a 4- fold increase in titer in the post-baseline period. A persistent positive response was defined as a TE ADA positive response detected in at least 2 consecutive post-baseline samples separated by at least a 12-week period. Persistent positive response was only analyzed for participants with positive TE ADA response. (NCT03510884)
Timeframe: Up to 24 weeks

InterventionParticipants (Count of Participants)
TE ADA positive responsePersistent positive response
DB Period: Alirocumab Q2W30

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DB Period: Percent Change From Baseline in Apolipoprotein A1 at Weeks 12 and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM mode, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12 and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-1.71.0
DB Period: Alirocumab Q4W5.04.4
DB Period: Placebo Q2W-0.1-0.1
DB Period: Placebo Q4W-0.7-4.5

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DB Period: Percent Change From Baseline in Apolipoprotein B at Weeks 12 and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12 and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-30.0-27.4
DB Period: Alirocumab Q4W-31.7-34.3
DB Period: Placebo Q2W8.910.4
DB Period: Placebo Q4W1.1-3.6

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DB Period: Percent Change From Baseline in Fasting Triglycerides at Weeks 12 and 24: On-treatment Estimand

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline on-treatment data up to Week 12 and Week 24, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. (NCT03510884)
Timeframe: Baseline, Weeks 12, and 24

,,,
Interventionpercent change (Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-2.211.9
DB Period: Alirocumab Q4W-0.3-6.8
DB Period: Placebo Q2W6.57.7
DB Period: Placebo Q4W7.812.2

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DB Period: Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Weeks 12, and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st investigational medicinal product (IMP) injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12, and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-34.8-33.6
DB Period: Alirocumab Q4W-39.2-38.2
DB Period: Placebo Q2W10.79.7
DB Period: Placebo Q4W2.3-4.4

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DB Period: Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Weeks 12 and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 day otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12, and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W3.55.6
DB Period: Alirocumab Q4W4.03.4
DB Period: Placebo Q2W-2.2-0.8
DB Period: Placebo Q4W-3.5-1.1

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DB Period: Percent Change From Baseline in Lipoprotein (a) at Weeks 12 and 24: On-treatment Estimand

Adjusted means and standard errors were obtained from a multiple imputation approach followed by a robust regression model including all available post-baseline on-treatment data up to Week 12 and Week 24, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for those who stopped IMP before switch to Q2W regimen, + 21 days otherwise. Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. (NCT03510884)
Timeframe: Baseline, Weeks 12 and 24

,,,
Interventionpercent change (Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-12.746-14.748
DB Period: Alirocumab Q4W-16.042-22.418
DB Period: Placebo Q2W-7.0990.492
DB Period: Placebo Q4W-2.5452.468

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DB Period: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol at Weeks 12 and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12 and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-33.0-31.0
Db Period: Alirocumab Q4W-34.7-35.6
DB Period: Placebo Q2W9.89.7
DB Period: Placebo Q4W2.8-3.7

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DB Period: Percent Change From Baseline in Total Cholesterol at Weeks 12 and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. MMRM model was run on participants with a Baseline value and at one on-treatment post-baseline value for a timepoint used in the model. (NCT03510884)
Timeframe: Baseline, Weeks 12 and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 12Week 24
DB Period: Alirocumab Q2W-25.3-23.4
DB Period: Alirocumab Q4W-27.0-27.7
DB Period: Placebo Q2W7.57.4
DB Period: Placebo Q4W0.9-4.4

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DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: ITT Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline data available up to Week 8, Week 12 and Week 24 were used and missing data were accounted for by the MMRM model. (NCT03510884)
Timeframe: Baseline to Weeks 8, 12 and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 8Week 12Week 24
DB Period: Alirocumab Q2W-35.4-34.8-33.6
DB Period: Alirocumab Q4W-42.0-39.2-38.2
DB Period: Placebo Q2W7.110.79.7
DB Period: Placebo Q4W-3.82.3-4.4

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DB Period: Percent Change in Low Density Lipoprotein Cholesterol From Baseline to Weeks 8, 12 and 24: On-treatment Estimand

Adjusted LS means and SE were obtained from MMRM model. All post-baseline on-treatment data available up to Week 8, Week 12 and Week 24 were used for the MMRM model, i.e., for Q2W data: from 1st IMP injection up to last IMP injection + 21 days and for Q4W data: from 1st IMP injection up to last IMP injection + 35 days for who stopped IMP before switch to Q2W regimen, + 21 days otherwise. (NCT03510884)
Timeframe: Baseline to Weeks 8, 12 and 24

,,,
Interventionpercent change (Least Squares Mean)
Week 8Week 12Week 24
DB Period: Alirocumab Q2W-35.4-34.8-33.6
DB Period: Alirocumab Q4W-42.0-39.2-38.2
DB Period: Placebo Q2W7.110.79.7
DB Period: Placebo Q4W-3.82.3-4.4

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Change in the Weekly Frequency of Bowel Movements Measured Between Baseline and the Second Week of Treatment

Change in the weekly frequency of bowel movements measured between baseline and the second week of treatment. Baseline is defined as the second week of screening for treatment period 1 and second week of washout for treatment period 2. (NCT04046328)
Timeframe: Baseline and Week 2 of treatment (Days 8 to 14, and Days 36 to 42)

InterventionWeekly bowel movements (Mean)
"Low Dose ECC Regimen"-11.5
"High Dose ECC Regimen"-13.4

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Mean Daily Dose of Loperamide in mg, if Used, During the Second Week of Treatment

(NCT04046328)
Timeframe: Days 8 to 14, and Days 36 to 42

Interventionmg (Mean)
"Low Dose ECC Regimen"72.9
"High Dose ECC Regimen"68.9

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Mean Daily Stool Form Score According to the BSFS (Bristol Stool Form Scale), Measured During the Second Week of Treatment

The BSFS classifies the form of human feces into seven categories (Type 1 to Type 7) based on stool shape and consistency. Types or scores of 1 and 2 indicate constipation, with 3 and 4 being the ideal stools as they are easy to defecate while not containing excess liquid, 5 tending towards diarrhea, and 6 and 7 indicate diarrhea. (NCT04046328)
Timeframe: Days 8 to 14, and Days 36 to 42

InterventionScore on BSFS scale (Mean)
"Low Dose ECC Regimen"3.6
"High Dose ECC Regimen"3.7

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Total Number of Bowel Movements for the Whole 2-week Treatment Period

(NCT04046328)
Timeframe: Days 1 to 14 and Days 29 to 42

InterventionBowel movements (Mean)
"Low Dose ECC Regimen"52.5
"High Dose ECC Regimen"55.1

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