glycine and Disease Exacerbation studies

Research Excerpts

Excerpt	Relevance	Reference
"On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease."	9.51	FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation. ( Beaver, JA; Casak, SJ; Charlab, R; Chow, ECY; Fashoyin-Aje, LA; Fesenko, N; Kluetz, PG; Lemery, SJ; Liu, J; Pazdur, R; Pierce, WF; Pradhan, S; Ren, Y; Shen, YL; Xiong, Y; Xu, Y; Zirklelbach, JF, 2022)
"The aim of this analysis was to assess healthcare resource utilization in the pivotal phase 3 TOURMALINE-MM1 study of the oral proteasome inhibitor ixazomib or placebo plus lenalidomide and dexamethasone (Rd) in relapsed and/or refractory multiple myeloma (RRMM)."	9.27	Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma. ( Berg, D; Hari, P; Lin, HM; Moreau, P; Richardson, PG; Zhu, Y, 2018)
"The purpose of this paper was to investigate the effect of the oral administration of L-glycine (Gly) on the development of diabetic cataract induced by streptozotocin (STZ) in rats."	7.78	Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. ( Aldavood, SJ; Bahmani, F; Bathaie, SZ; Ghahghaei, A, 2012)
"Classic neonatal-onset glycine encephalopathy (GE) is devastating and life threatening."	7.73	Mild glycine encephalopathy (NKH) in a large kindred due to a silent exonic GLDC splice mutation. ( Flusser, H; Galil, A; Korman, SH; Kure, S; Matsubara, Y; Sato, K, 2005)
"To report two unrelated patients with a new phenotype of nonketotic hyperglycinemia associated with idiopathic pulmonary hypertension."	7.73	Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension. ( Arranz, JA; del Toro, M; Kure, S; Macaya, A; Matsubara, Y; Moreno, A; Ortega, A; Raspall, M; Riudor, E; Roig, M; Vazquez, E, 2006)
" Methods Logistic regression was used to investigate relationships between ixazomib plasma exposure (area under the curve/day; derived from individual apparent clearance values from a published population pharmacokinetic analysis) and safety/efficacy outcomes (hematologic [grade ≥ 3 vs ≤ 2] or non-hematologic [grade ≥ 2 vs ≤ 1] adverse events [AEs], and clinical benefit [≥stable disease vs progressive disease]) using phase 1 data in relapsed/refractory MM (NCT00963820; N = 44)."	6.82	Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study. ( Gupta, N; Hui, AM; Labotka, R; Liu, G; Venkatakrishnan, K, 2016)
"On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease."	5.51	FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation. ( Beaver, JA; Casak, SJ; Charlab, R; Chow, ECY; Fashoyin-Aje, LA; Fesenko, N; Kluetz, PG; Lemery, SJ; Liu, J; Pazdur, R; Pierce, WF; Pradhan, S; Ren, Y; Shen, YL; Xiong, Y; Xu, Y; Zirklelbach, JF, 2022)
"Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow."	5.51	Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice. ( Deng, Q; Gong, Z; Hu, H; Li, Y; Liu, M; Lu, Z; Ma, X; Wang, L; Xu-Monette, ZY; Young, KH; Zhang, S, 2019)
"Glycine is an amino acid involved in antioxidative reactions, purine synthesis, and collagen formation."	5.42	Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. ( Ding, Y; Gregory, JF; Nygård, OK; Pedersen, ER; Svingen, GF; Tell, GS; Ueland, PM, 2015)
"Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma."	5.30	Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. ( Beksac, M; Chng, WJ; Dash, AB; Dimopoulos, MA; Gay, F; Goldschmidt, H; Gupta, N; Hajek, R; Iida, S; Kaiser, M; Labotka, R; Maisnar, V; Mateos, MV; Min, CK; Moreau, P; Morgan, G; Palumbo, A; Pluta, A; Rajkumar, SV; Schjesvold, F; Skacel, T; Spencer, A; Suryanarayan, K; Teng, Z; Weisel, KC; Zweegman, S, 2019)
"The aim of this analysis was to assess healthcare resource utilization in the pivotal phase 3 TOURMALINE-MM1 study of the oral proteasome inhibitor ixazomib or placebo plus lenalidomide and dexamethasone (Rd) in relapsed and/or refractory multiple myeloma (RRMM)."	5.27	Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma. ( Berg, D; Hari, P; Lin, HM; Moreau, P; Richardson, PG; Zhu, Y, 2018)
"The purpose of this paper was to investigate the effect of the oral administration of L-glycine (Gly) on the development of diabetic cataract induced by streptozotocin (STZ) in rats."	3.78	Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. ( Aldavood, SJ; Bahmani, F; Bathaie, SZ; Ghahghaei, A, 2012)
" Despite similar clinical asthma scores on hospital admission, the children with the Gly/Gly genotype had significantly shorter hospital ICU length of stay and duration of continuously nebulized albuterol therapy and were significantly less likely to require IV beta(2)-AR therapy than those with Arg/Arg or Arg/Gly genotypes."	3.75	Beta2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. ( Carroll, CL; Schramm, CM; Stoltz, P; Zucker, AR, 2009)
"Classic neonatal-onset glycine encephalopathy (GE) is devastating and life threatening."	3.73	Mild glycine encephalopathy (NKH) in a large kindred due to a silent exonic GLDC splice mutation. ( Flusser, H; Galil, A; Korman, SH; Kure, S; Matsubara, Y; Sato, K, 2005)
"To report two unrelated patients with a new phenotype of nonketotic hyperglycinemia associated with idiopathic pulmonary hypertension."	3.73	Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension. ( Arranz, JA; del Toro, M; Kure, S; Macaya, A; Matsubara, Y; Moreno, A; Ortega, A; Raspall, M; Riudor, E; Roig, M; Vazquez, E, 2006)
" NKH is classically associated with neonatal apnea, lethargy, hypotonia, and seizures, followed by severe psychomotor retardation in those who survive."	3.72	Natural history of nonketotic hyperglycinemia in 65 patients. ( Applegarth, D; Hamosh, A; Hoover-Fong, JE; Shah, S; Toone, J; Van Hove, JL, 2004)
" Methods Logistic regression was used to investigate relationships between ixazomib plasma exposure (area under the curve/day; derived from individual apparent clearance values from a published population pharmacokinetic analysis) and safety/efficacy outcomes (hematologic [grade ≥ 3 vs ≤ 2] or non-hematologic [grade ≥ 2 vs ≤ 1] adverse events [AEs], and clinical benefit [≥stable disease vs progressive disease]) using phase 1 data in relapsed/refractory MM (NCT00963820; N = 44)."	2.82	Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study. ( Gupta, N; Hui, AM; Labotka, R; Liu, G; Venkatakrishnan, K, 2016)
"Alternate-day oral dosing of PF-04929113 at 74 mg/m(2) for 21/28 days was generally well tolerated with reversible toxicity."	2.78	Phase I trial of the HSP90 inhibitor PF-04929113 (SNX5422) in adult patients with recurrent, refractory hematologic malignancies. ( Brega, N; Hinson, JM; Houk, BE; Jillela, A; Reddy, N; Voorhees, PM, 2013)
" Mean absolute oral bioavailability ranged from 13·9% (fed) to 34·8% (fasting) in 12 patients treated at the 560 mg b."	2.78	Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes. ( Komrokji, RS; Lancet, JE; List, AF; Maniar, M; Raza, A; Ren, C; Taft, D; Wilhelm, F, 2013)
"The Arg388 allele increased prostate cancer risk compared with Gly388 allele (OR = 1."	2.47	FGFR4 Gly388Arg polymorphism contributes to prostate cancer development and progression: a meta-analysis of 2618 cases and 2305 controls. ( Chen, M; Chen, SQ; Hua, LX; Tong, N; Wang, ZJ; Xu, B; Zhang, ZD, 2011)
"Each glycine (Gly) copy was associated with a higher number of exacerbations (OR: 0."	1.72	Clinical course of COPD in patients with Arg16Gly (rs1042713) polymorphism of ADRB2 gene. ( Dmytriiev, K; Mostovoy, Y; Slepchenko, N; Smereka, Y, 2022)
"Meningiomas are common brain tumours that are usually defined by benign clinical course."	1.62	Metabolic alterations in meningioma reflect the clinical course. ( Beck, J; Daka, K; Delev, D; Grauvogel, J; Heiland, DH; Krüger, MT; Masalha, W; Pompe, N; Schnell, O; Weber, S; Woerner, J, 2021)
"Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in developed countries."	1.56	Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease. ( Caussy, C; Loomba, R; Mills, PJ, 2020)
"Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow."	1.51	Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice. ( Deng, Q; Gong, Z; Hu, H; Li, Y; Liu, M; Lu, Z; Ma, X; Wang, L; Xu-Monette, ZY; Young, KH; Zhang, S, 2019)
"Glycine is an amino acid involved in antioxidative reactions, purine synthesis, and collagen formation."	1.42	Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. ( Ding, Y; Gregory, JF; Nygård, OK; Pedersen, ER; Svingen, GF; Tell, GS; Ueland, PM, 2015)
"Atherosclerosis is a multifactorial and progressive disease commonly correlated with a high fat diet."	1.40	Serum metabonomic analysis of apoE(-/-) mice reveals progression axes for atherosclerosis based on NMR spectroscopy. ( Guo, J; Li, J; Li, X; Liu, Y; Wang, L; Wu, T; Yang, Y; Yuan, F; Zhang, Q; Zheng, L, 2014)
"We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming."	1.37	Retinal remodeling in the Tg P347L rabbit, a large-eye model of retinal degeneration. ( Anderson, J; Jones, BW; Kondo, M; Lin, Y; Marc, RE; Rapp, K; Shaw, MV; Terasaki, H; Watt, CB; Yang, JH, 2011)
"One form of chronic polymerase gamma-encephalopathy, that is associated with the c."	1.36	Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes. ( Bindoff, LA; Engelsen, BE; Ersland, L; Moen, G; Mørk, SJ; Neckelmann, G; Tzoulis, C; Viscomi, C; Zeviani, M, 2010)
"Spinal cord injury-induced spasticity, in the tail musculature, does not appear to involve either an increase in monosynaptic glutamatergic inputs from myelinated afferents or a decrease in glycinergic inputs to sacrocaudal motoneurons."	1.34	VGLUT1 and GLYT2 labeling of sacrocaudal motoneurons in the spinal cord injured spastic rat. ( Kitzman, P, 2007)
"The muraglitazar-treated mice had normal plasma glucose, and insulin levels, equivalent or higher pancreatic insulin content than normal mice, showed a robust insulin response to glucose and exhibited greater glucose tolerance."	1.34	The dual peroxisome proliferator-activated receptor alpha/gamma activator muraglitazar prevents the natural progression of diabetes in db/db mice. ( Belder, R; Chen, S; Cheng, PT; Devasthale, P; Egan, D; Farrelly, D; French, M; Gu, L; Hariharan, N; Harrity, T; Janovitz, E; Kunselman, L; Peters, A; Ponticiello, R; Staal, A; Swartz, J; Taylor, S; Tozzo, E; Welzel, G; Whaley, J; Zebo, R, 2007)
"His glycine index was 0."	1.34	Neonatal nonketotic hyperglycinemia. ( Bhamkar, RP; Colaco, P, 2007)
"Acute colitis was induced in mice by administration of 1."	1.33	Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis. ( Chinen, H; Hibi, T; Hisamatsu, T; Inoue, N; Iwao, Y; Kamada, N; Matsuoka, K; Morohoshi, Y; Ogata, H; Okamoto, S; Sato, T; Takaishi, H, 2006)
" We conclude that SNPs in PPARD modify the conversion from IGT to type 2 diabetes, particularly in combination with the SNPs of PGC-1A and PPARG2."	1.33	Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser substitution of PGC-1A and the Pro12Ala substitution of PPARG2 predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. ( Andrulionyte, L; Chiasson, JL; Laakso, M; Peltola, P, 2006)
"Neonatal-type nonketotic hyperglycinemia treatment remains unsatisfactory, even if started early."	1.32	Poor outcome for neonatal-type nonketotic hyperglycinemia treated with high-dose sodium benzoate and dextromethorphan. ( Chien, YH; Chou, SP; Hsu, CC; Huang, A; Hwu, WL; Lee, WT; Lu, FL, 2004)
"Amyotrophic lateral sclerosis (ALS), a multifactorial disease characterized by diffuse motor neuron degeneration, has proven to be a difficult target for stem cell therapy."	1.32	Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. ( Chen, N; Davis, CD; Garbuzova-Davis, S; Hudson, JE; Justen, EB; Lane, JC; Sanberg, PR; Saporta, S; Willing, AE; Zigova, T, 2003)
"One female patient with amyotrophic lateral sclerosis (ALS) was heterozygous for G12R mutation."	1.32	[Peculiarities of sporadic motor neuron disease associated with D90A and G12R mutations in Russian population]. ( Alekhin, AV; Brusov, OS; Karakhan, VB; Kondrat'eva, EA; Levitskaia, NI; Levitskiĭ, GN; Limborskaia, SA; Lysko, AI; Serdiuk, AV; Shadrina, MI; Skvortsova, VI; Slominskiĭ, PA, 2003)
"Circulating tumor cells were identified in all four patients."	1.31	K-ras mutational analysis of polyclonal colorectal cancers identifies uniclonal circulating tumor cells. ( Krygier, S; Luchtefeld, MA; Senagore, AJ; Thebo, JS, 2001)

Research

Studies (74)

Authors

Clinical Trials (17)

Trial Overview

Trial Outcomes

Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	1 (1.35)	18.2507
2000's	39 (52.70)	29.6817
2010's	26 (35.14)	24.3611
2020's	8 (10.81)	2.80

Authors	Studies
Chen, T	1
Zhou, K	1
Sun, T	1
Sang, C	1
Jia, W	1
Xie, G	1
Casak, SJ	1
Pradhan, S	1
Fashoyin-Aje, LA	1
Ren, Y	1
Shen, YL	1
Xu, Y	1
Chow, ECY	1
Xiong, Y	1
Zirklelbach, JF	1
Liu, J	1
Charlab, R	1
Pierce, WF	1
Fesenko, N	1
Beaver, JA	1
Pazdur, R	1
Kluetz, PG	1
Lemery, SJ	1
Dmytriiev, K	1
Mostovoy, Y	1
Slepchenko, N	1
Smereka, Y	1
Chen, Z	1
Nan, H	1
Kong, Y	1
Chu, M	1
Liu, L	1
Zhang, J	1
Wang, L	3
Wu, L	1
Blombery, P	1
Thompson, ER	1
Nguyen, T	1
Birkinshaw, RW	1
Gong, JN	1
Chen, X	1
McBean, M	1
Thijssen, R	1
Conway, T	1
Anderson, MA	1
Seymour, JF	1
Westerman, DA	1
Czabotar, PE	1
Huang, DCS	1
Roberts, AW	1
Abou-Alfa, GK	1
Macarulla, T	1
Javle, MM	1
Kelley, RK	1
Lubner, SJ	1
Adeva, J	1
Cleary, JM	1
Catenacci, DV	1
Borad, MJ	1
Bridgewater, J	1
Harris, WP	1
Murphy, AG	1
Oh, DY	1
Whisenant, J	1
Lowery, MA	1
Goyal, L	1
Shroff, RT	1
El-Khoueiry, AB	1
Fan, B	1
Wu, B	1
Chamberlain, CX	1
Jiang, L	1
Gliser, C	1
Pandya, SS	1
Valle, JW	1
Zhu, AX	1
Masalha, W	1
Daka, K	1
Woerner, J	1
Pompe, N	1
Weber, S	1
Delev, D	1
Krüger, MT	1
Schnell, O	1
Beck, J	1
Heiland, DH	1
Grauvogel, J	1
Navada, SC	2
Fruchtman, SM	1
Odchimar-Reissig, R	1
Demakos, EP	1
Petrone, ME	1
Zbyszewski, PS	1
Holland, JF	1
Silverman, LR	2
Hari, P	1
Lin, HM	1
Zhu, Y	1
Berg, D	1
Richardson, PG	1
Moreau, P	2
Homma, S	1
Bando, M	1
Azuma, A	1
Sakamoto, S	1
Sugino, K	1
Ishii, Y	1
Izumi, S	1
Inase, N	1
Inoue, Y	1
Ebina, M	1
Ogura, T	2
Kishi, K	1
Kishaba, T	1
Kido, T	1
Gemma, A	1
Goto, Y	1
Sasaki, S	1
Johkoh, T	1
Suda, T	1
Takahashi, K	1
Takahashi, H	2
Taguchi, Y	1
Date, H	1
Taniguchi, H	1
Nakayama, T	1
Nishioka, Y	1
Hasegawa, Y	1
Hattori, N	1
Fukuoka, J	1
Miyamoto, A	1
Mukae, H	1
Yokoyama, A	1
Yoshino, I	1
Watanabe, K	1
Dimopoulos, MA	2
Grosicki, S	1
Jędrzejczak, WW	1
Nahi, H	1
Gruber, A	1
Hansson, M	1
Gupta, N	3
Byrne, C	1
Labotka, R	3
Teng, Z	2
Yang, H	1
Grzasko, N	1
Kumar, S	1
Gay, F	1
Schjesvold, F	1
Beksac, M	1
Hajek, R	1
Weisel, KC	1
Goldschmidt, H	1
Maisnar, V	1
Min, CK	1
Pluta, A	1
Chng, WJ	1
Kaiser, M	1
Zweegman, S	1
Mateos, MV	1
Spencer, A	1
Iida, S	1
Morgan, G	1
Suryanarayan, K	1
Skacel, T	1
Palumbo, A	1
Dash, AB	1
Rajkumar, SV	1
Mills, PJ	1
Caussy, C	1
Loomba, R	1
Deng, Q	1
Hu, H	1
Liu, M	1
Gong, Z	1
Zhang, S	1
Xu-Monette, ZY	1
Lu, Z	1
Young, KH	1
Ma, X	1
Li, Y	2
Reddy, N	1
Voorhees, PM	1
Houk, BE	1
Brega, N	1
Hinson, JM	1
Jillela, A	1
Komrokji, RS	1
Raza, A	1
Lancet, JE	1
Ren, C	1
Taft, D	1
Maniar, M	1
Wilhelm, F	1
List, AF	1
Timmer, NM	1
Metaxas, A	1
van der Stelt, I	1
Kluijtmans, LA	1
van Berckel, BN	1
Verbeek, MM	1
Sakai, M	1
Takenami, T	1
Otsuka, T	1
Hayashi, N	1
Yoshino, K	1
Matsumoto, S	2
Okamoto, H	1
Yahalom, G	1
Orlev, Y	1
Cohen, OS	1
Kozlova, E	1
Friedman, E	1
Inzelberg, R	1
Hassin-Baer, S	1
Yang, Y	1
Liu, Y	1
Zheng, L	1
Wu, T	1
Li, J	1
Zhang, Q	1
Li, X	1
Yuan, F	1
Guo, J	1
Panagiotou, OA	1
Travis, RC	1
Campa, D	1
Berndt, SI	1
Lindstrom, S	1
Kraft, P	1
Schumacher, FR	1
Siddiq, A	1
Papatheodorou, SI	1
Stanford, JL	1
Albanes, D	1
Virtamo, J	1
Weinstein, SJ	1
Diver, WR	1
Gapstur, SM	1
Stevens, VL	1
Boeing, H	1
Bueno-de-Mesquita, HB	1
Barricarte Gurrea, A	1
Kaaks, R	1
Khaw, KT	1
Krogh, V	1
Overvad, K	1
Riboli, E	1
Trichopoulos, D	1
Giovannucci, E	1
Stampfer, M	1
Haiman, C	1
Henderson, B	1
Le Marchand, L	1
Gaziano, JM	1
Hunter, DJ	1
Koutros, S	1
Yeager, M	1
Hoover, RN	1
Chanock, SJ	1
Wacholder, S	1
Key, TJ	1
Tsilidis, KK	1
Schänzer, A	1
Kimmich, C	1
Röcken, C	1
Haverkamp, T	1
Weidner, I	1
Acker, T	1
Krämer, HH	1
Ding, Y	1
Svingen, GF	1
Pedersen, ER	1
Gregory, JF	1
Ueland, PM	1
Tell, GS	1
Nygård, OK	1
Liu, G	1
Hui, AM	1
Venkatakrishnan, K	1
Ji, L	1
Li, L	1
Qu, F	1
Zhang, G	1
Wang, Y	1
Bai, X	1
Pan, S	1
Xue, D	1
Wang, G	1
Sun, B	1
Pace, RA	1
Peat, RA	1
Baker, NL	1
Zamurs, L	1
Mörgelin, M	1
Irving, M	1
Adams, NE	1
Bateman, JF	1
Mowat, D	1
Smith, NJ	1
Lamont, PJ	1
Moore, SA	1
Mathews, KD	1
North, KN	1
Lamandé, SR	1
Carroll, CL	1
Stoltz, P	1
Schramm, CM	1
Zucker, AR	1
Rönnbäck, A	1
Zhu, S	1
Dillner, K	1
Aoki, M	1
Lilius, L	1
Näslund, J	1
Winblad, B	1
Graff, C	1
Schirrmeister, W	1
Gnad, T	1
Wex, T	1
Higashiyama, S	1
Wolke, C	1
Naumann, M	1
Lendeckel, U	1
D'Ambrosi, N	1
Finocchi, P	1
Apolloni, S	1
Cozzolino, M	1
Ferri, A	1
Padovano, V	1
Pietrini, G	1
Carrì, MT	1
Volonté, C	1
Tzoulis, C	1
Neckelmann, G	1
Mørk, SJ	1
Engelsen, BE	1
Viscomi, C	1
Moen, G	1
Ersland, L	1
Zeviani, M	1
Bindoff, LA	1
Yang, WW	1
Sidman, RL	1
Taksir, TV	1
Treleaven, CM	1
Fidler, JA	1
Cheng, SH	1
Dodge, JC	1
Shihabuddin, LS	1
Xu, B	1
Tong, N	1
Chen, SQ	1
Hua, LX	1
Wang, ZJ	1
Zhang, ZD	1
Chen, M	1
Jones, BW	1
Kondo, M	1
Terasaki, H	1
Watt, CB	1
Rapp, K	1
Anderson, J	1
Lin, Y	1
Shaw, MV	1
Yang, JH	1
Marc, RE	1
Jung, CW	1
Lee, BH	1
Kim, JH	1
Kim, GH	1
Lee, J	1
Choi, JH	1
Yoo, HW	1
Liang, H	1
Ward, WF	1
Jang, YC	1
Bhattacharya, A	1
Bokov, AF	1
Jernigan, A	1
Richardson, A	1
Van Remmen, H	1
Bahmani, F	1
Bathaie, SZ	1
Aldavood, SJ	1
Ghahghaei, A	1
Squitieri, F	1
Cannella, M	1
Simonelli, M	1
Garbuzova-Davis, S	1
Willing, AE	1
Zigova, T	1
Saporta, S	1
Justen, EB	1
Lane, JC	1
Hudson, JE	1
Chen, N	1
Davis, CD	1
Sanberg, PR	1
Al-Hassnan, ZN	1
Boyadjiev, SA	1
Praphanphoj, V	1
Hamosh, A	2
Braverman, NE	1
Thomas, GH	1
Geraghty, MT	1
Plass, JR	1
Mol, O	1
Heegsma, J	1
Geuken, M	1
de Bruin, J	1
Elling, G	1
Müller, M	1
Faber, KN	1
Jansen, PL	1
Skvortsova, VI	1
Limborskaia, SA	1
Slominskiĭ, PA	1
Levitskiĭ, GN	1
Levitskaia, NI	1
Shadrina, MI	1
Kondrat'eva, EA	1
Brusov, OS	1
Lysko, AI	1
Karakhan, VB	1
Alekhin, AV	1
Serdiuk, AV	1
Chien, YH	1
Hsu, CC	1
Huang, A	1
Chou, SP	1
Lu, FL	1
Lee, WT	1
Hwu, WL	1
Street, VA	1
Kallman, JC	1
Kiemele, KL	1
Völkel, H	1
Selzle, M	1
Walk, T	1
Jung, G	1
Link, J	1
Ludolph, AC	1
Reuter, A	1
Yamada, G	1
Wang, J	2
Stockton, DW	1
Ittmann, M	1
Hoover-Fong, JE	1
Shah, S	1
Van Hove, JL	1
Applegarth, D	1
Toone, J	1
Flusser, H	1
Korman, SH	1
Sato, K	1
Matsubara, Y	2
Galil, A	1
Kure, S	2
Kroner, A	1
Vogel, F	1
Kolb-Mäurer, A	1
Kruse, N	1
Toyka, KV	1
Hemmer, B	1
Rieckmann, P	1
Mäurer, M	1
Stadler, CR	1
Knyazev, P	1
Bange, J	2
Ullrich, A	2
Müller, T	1
Deschauer, M	1
Neudecker, S	1
Zierz, S	1
Morohoshi, Y	1
Matsuoka, K	1
Chinen, H	1
Kamada, N	1
Sato, T	1
Hisamatsu, T	1
Okamoto, S	1
Inoue, N	1
Takaishi, H	1
Ogata, H	1
Iwao, Y	1
Hibi, T	1
del Toro, M	1
Arranz, JA	1
Macaya, A	1
Riudor, E	1
Raspall, M	1
Moreno, A	1
Vazquez, E	1
Ortega, A	1
Roig, M	1
Andrulionyte, L	1
Peltola, P	1
Chiasson, JL	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of AG-120 in Previously-treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation[NCT02989857]	Phase 3	187 participants (Actual)	Interventional	2017-02-20	Completed
Phase I Dose Escalation Study of ON 01910.Na With Increasing Duration of an Initial 3-Day Continuous Infusion in Patients With Refractory Leukemia or MDS[NCT00854646]	Phase 1	22 participants (Actual)	Interventional	2008-10-31	Completed
An Open-Label, Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma Requiring Systemic Treatment[NCT02046070]	Phase 2	148 participants (Actual)	Interventional	2014-03-05	Completed
A Multicenter, Open-label, Prospective Study of Ixazomib, Lenalidomide, and Ixazomib in Combination With Lenalidomide for Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma[NCT04217967]	Phase 4	180 participants (Anticipated)	Interventional	2020-01-03	Recruiting
A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant[NCT02181413]	Phase 3	656 participants (Actual)	Interventional	2014-07-01	Active, not recruiting
The Effects of Glycine on Atherosclerosis and Metabolic Syndrome-related Parameters: A Clinical and Ex-vivo Study.[NCT03850314]	Phase 2/Phase 3	50 participants (Anticipated)	Interventional	2019-03-31	Not yet recruiting
A Randomised Double Blind Study of the Effects of Homocysteine Lowering Therapy on Mortality and Cardiac Events in Patients Undergoing Coronary Angiography[NCT00354081]	Phase 3	3,096 participants (Actual)	Interventional	1999-04-30	Completed
Effects of Dietary Amino Acids on Serum and Macrophage Atherogenicity[NCT03180775]		110 participants (Anticipated)	Interventional	2017-07-01	Not yet recruiting
A Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Intermediate-1, Myelodysplastic Syndrome Patients Based on the International Prognostic Scoring System[NCT01904682]	Phase 2	45 participants (Actual)	Interventional	2013-07-31	Completed
A Phase I/II, Multi-center, Dose-escalating Study of the Tolerability, Pharmacokinetics, and Clinical Activity of the Combined Administration of Oral Rigosertib With Azacitidine in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia[NCT01926587]	Phase 1/Phase 2	45 participants (Actual)	Interventional	2013-08-31	Completed
A Phase III, International, Randomized, Controlled Study of Rigosertib Versus Physician's Choice of Treatment in Patients With Myelodysplastic Syndrome After Failure of a Hypomethylating Agent[NCT02562443]	Phase 3	372 participants (Actual)	Interventional	2015-12-02	Terminated (stopped due to Top line analysis indicated that the study had failed to achieve its primary endpoint.)
Phase III MultiCenter Randomized Controlled Study to Assess Efficacy and Safety of ON 01910.Na 72-Hr Continuous IV Infusion in MDS Patients With Excess Blasts Relapsing After or Refractory to or Intolerant to Azacitidine or Decitabine[NCT01241500]	Phase 3	299 participants (Actual)	Interventional	2010-11-30	Completed
A Phase II, Multicenter, Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent Low or Intermediate-1 (Any Cytogenetics) or Trisomy 8 Intermediate-2 Myelodysplastic Syndrome Patients Based on IPSS Classification[NCT01584531]	Phase 2	82 participants (Actual)	Interventional	2012-05-31	Completed
A Phase 2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Myelodysplastic Syndrome Patients With Trisomy 8 or Classified as Intermediate-1, 2 or High Risk[NCT00906334]	Phase 2	14 participants (Actual)	Interventional	2009-05-31	Completed
A Phase 1/2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)[NCT00854945]	Phase 1/Phase 2	36 participants (Actual)	Interventional	2009-01-31	Completed
Phase 1 Study to Assess Tolerability, PK and PD Activity of ON 01910.Na Administered Orally as Escalating Single and Multiple Doses Twice a Day up to 14 Days of a 21-Day Cycle in Patients With Myelodysplastic Syndrome[NCT01048619]	Phase 1	36 participants (Actual)	Interventional	2009-12-31	Completed
Intermittent Fasting as a Primary Means for Improving Quality of Life for Acute and Chronic Pancreatitis[NCT04760847]		64 participants (Anticipated)	Interventional	2023-12-07	Not yet recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

Accumulation Ratio Based on Cmax (Racc Cmax)

Intervention	ratio (Mean)
Randomization Phase AG-120 Plus Cross Over Phase AG-120	1.6881

Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)

Intervention	ratio (Mean)
Randomization Phase AG-120 Plus Cross Over Phase AG-120	1.2369

Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose of Cycle 2 Day 1 (each cycle = 28 days)

Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score

Intervention	h*ng/mL (Mean)
Randomization Phase AG-120 Plus Cross Over Phase AG-120	91219.4

"The EQ visual analogue scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled The best health you can imagine and The worst health you can imagine. Responses are marked on a 0-100 scale with higher scores indicating higher health-related quality of life (i.e., better outcome)." (NCT02989857)
Timeframe: Cycle 3 Day 1

DOR as Assessed by the IRC Per RECIST v1.1

Intervention	score on a scale (Mean)
AG-120	4.6
Placebo	-2.8

DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation. (NCT02989857)
Timeframe: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)

Duration of Response (DOR) as Assessed by the Investigator

Intervention	months (Median)
AG-120	NA

DOR was defined as the time in months from date of first documented CR or PR to date of first documented disease progression or death due to any cause, whichever is earlier, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Participants with response and without progression were censored at the last observation. (NCT02989857)
Timeframe: From the date of first confirmed CR or PR to disease progression or death regardless of cause (Up to approximately 2 years)

Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1

Intervention	months (Median)
AG-120	NA
Placebo	NA

ORR as assessed by the investigator was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. (NCT02989857)
Timeframe: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)

ORR as Assessed by the IRC Per RECIST v1.1

Intervention	percentage of participants (Number)
AG-120	3.2
Placebo	1.6

ORR as assessed by the IRC was defined as the percentage of participants with a best overall response (BOR) defined as complete response (CR) or partial response (PR) per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. (NCT02989857)
Timeframe: From the date of randomization up to confirmed CR or PR (Up to approximately 2 years)

Overall Survival (OS)

Intervention	percentage of participants (Number)
AG-120	2.4
Placebo	0

Overall survival was defined as the time in months from date of randomization to the date of death due to any cause. Participants without documentation of death at the time of the final collection were censored at the date the participant was last known to be alive, or the final collection date, whichever is earlier. (NCT02989857)
Timeframe: From date of randomization until the date of death due to any cause (Up to approximately 2 years)

Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment

Intervention	months (Median)
AG-120	10.3
Placebo	7.5

Concomitant medications were medications that were ongoing or initiated after the first dose of the study drug but before the last dose plus 28 days. Percentage of participants who required at least one concomitant medications during the study along with their prescribed study drug (AG-120 or placebo) were reported. (NCT02989857)
Timeframe: From first dose of study drug up to 28 days after last dose (Up to approximately 4 Years)

PFS as Determined by Investigator

Intervention	percentage of participants (Number)
AG-120	99.2
Placebo	98.3
After Crossover to AG-120	95.3

PFS was defined as the time from date of randomization to the date of first documented disease progression as assessed by the investigator using RECIST v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as ≥20% increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or the appearance of 1 or more new lesions. No progression or death by data cutoff date was censored at the last adequate assessment date. (NCT02989857)
Timeframe: From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough

Intervention	months (Median)
AG-120	2.7
Placebo	1.4

%BRtrough is the percent inhibition for Rtrough. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough

Intervention	percent (Mean)
Randomization Phase AG-120 Plus Cross Over Phase AG-120	73.726

Rtrough is the observed response value at the end of a dosing interval. Crossover C2D1 visit was combined with C2D1 visit for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 2 Day 1 (each cycle = 28 days)

Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)

Intervention	ng/mL (Mean)
Randomization Phase AG-120 Plus Cross Over Phase AG-120	97.66

PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions. (NCT02989857)
Timeframe: From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Time to Response (TTR) as Assessed by the Investigator

Intervention	months (Median)
AG-120	2.7
Placebo	1.4

TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the Investigator per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure. (NCT02989857)
Timeframe: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)

TTR as Assessed by the IRC Per RECIST v1.1

Intervention	months (Median)
AG-120	NA
Placebo	NA

TTR was defined as the time from date of randomization to date of first documented CR or PR for responders, as assessed by the IRC per RECIST v1.1. CR: disappearance of all target and non-target lesions (TLs) and all pathological lymph nodes (LNs) (target and non target), with short axis <10mm. PR: ≥30% decrease in sum of diameters (SOD) from Baseline. Only responders were analyzed for this outcome measure. (NCT02989857)
Timeframe: From the date of randomization up to the date of first documented CR or PR (Up to approximately 2 years)

Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)

Intervention	months (Median)
AG-120	NA

Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose of Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

Change From Baseline in Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 Subscales Scores

Intervention	h*ng/mL (Mean)
	Cycle 1 Day 1	Cycle 2 Day 1
Randomization Phase AG-120 Plus Cross Over Phase AG-120	10972.2	16651.7

EORTC-QLQ-C30 is the European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core Questionnaire. For EORTC QLQ-C30, subscales of physical functioning, pain, and appetite loss were assessed. These had 4 response levels (not at all, a little, quite a bit, and very much). For functional scales, higher scores=better QOL (positive change from Baseline=improvement). For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. (NCT02989857)
Timeframe: Cycle 2 Day 1 and Cycle 3 Day 1

Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)

Intervention	score on a scale (Least Squares Mean)
	Cycle 2 Day 1: Physical Functioning	Cycle 2 Day 1: Pain	Cycle 2 Day 1: Appetite Loss	Cycle 3 Day 1: Physical Functioning	Cycle 3 Day 1: Pain	Cycle 3 Day 1: Appetite Loss
AG-120	-2.4	2.2	7.9	-0.2	-1.2	-0.5
Placebo	-13.3	12.5	4.3	-12.6	-5.3	3.2

For HRQOL based on QLQ-BIL21, subscales of eating symptoms and pain symptoms were assessed. Each item is a 4-point Likert scale. There are 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For symptom scales, lower scores=better QOL (negative change from Baseline=improvement). (NCT02989857)
Timeframe: Cycle 2 Day 1 and Cycle 3 Day 1

Maximum Observed Plasma Concentration (Cmax) of AG-120

Intervention	score on a scale (Least Squares Mean)
	Cycle 2 Day 1: Pain	Cycle 2 Day 1: Appetite Loss	Cycle 3 Day 1: Pain	Cycle 3 Day 1: Appetite Loss
AG-120	5.1	4.3	2.3	-2.0
Placebo	10.1	3.6	-2.1	4.1

Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events

Intervention	ng/mL (Mean)
	Cycle 1 Day 1	Cycle 2 Day 1
Randomization Phase AG-120 Plus Cross Over Phase AG-120	4424.0	5050.5

The laboratory parameters evaluated by the investigator included hematology and chemistry. Laboratory abnormalities reported in this endpoint are Grade 3 or higher adverse events. Grading categories were determined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. (NCT02989857)
Timeframe: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)

Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events

Intervention	percentage of participants (Number)
	Anaemia	Platelet Count Decreased	Neutrophil Count Decreased	White Blood Cell Count Decreased	Lymphocyte Count Decreased	Thrombocytopenia	Blood Loss Anaemia	Blood Bilirubin Increased	Hyponatraemia	Aspartate Aminotransferase Increased	Hypophosphataemia	Hyperbilirubinaemia	Hyperkalaemia	Blood Alkaline Phosphatase Increased	Alanine Aminotransferase Increased	Hypoalbuminaemia	Gamma-glutamyltransferase Increased	Hypercalcaemia	Hyperuricaemia	Hypokalaemia	Transaminases Increased	Blood Uric Acid Increased
After Crossover to AG-120	9.3	2.3	0.0	0.0	0.0	0.0	0.0	7.0	2.3	4.7	4.7	0.0	2.3	0.0	2.3	0.0	0.0	0.0	0.0	2.3	0.0	0.0
AG-120	7.3	2.4	1.6	1.6	0.8	0.8	0.8	5.7	5.7	4.9	3.3	3.3	2.4	2.4	1.6	1.6	0.8	0.8	0.8	0.8	0.8	0.0
Placebo	0.0	0.0	0.0	0.0	3.4	0.0	0.0	1.7	10.2	1.7	5.1	0.0	3.4	5.1	0.0	1.7	1.7	1.7	0.0	1.7	0.0	1.7

(NCT02989857)
Timeframe: Pre-dose C1D1, C2D1; Post-dose C1D1, C1D15, C2D1 and Day 1 of C3D1 and all cycles thereafter up to last dose plus 28 days (Up to approximately 4 years)

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Intervention	percentage of participants (Number)
	Electrocardiogram QT Prolonged	Electrocardiogram Abnormal
After Crossover to AG-120	2.3	0.0
AG-120	9.8	0.8
Placebo	3.4	0.0

An AE is any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE or suspected adverse reaction is considered serious (an SAE) if it is fatal, life-threatening, causes in-patient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect in a neonate/infant born to a mother or father exposed to study treatment or is an important medical event. Treatment-emergent adverse events are reported. (NCT02989857)
Timeframe: From first dose of study drug up to 28 days after last dose for each intervention (Up to approximately 4 Years)

Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C)

Intervention	percentage of participants (Number)
	AEs	SAEs
After Crossover to AG-120	95.3	27.9
AG-120	97.6	35.0
Placebo	96.6	23.7

The PGI-C is a self-rated evaluative instrument for assessment across 3 domains (physical function, appetite loss, and pain). The PGI-C is measured using a 7-point Likert scale, with 6= very much better, 5= moderately better, 4= a little better, 3= no change, 2= a little worse, 1= moderately worse, and 0= very much worse. A lower score indicates a worse outcome. Percentages are rounded off to whole number at the nearest decimal. (NCT02989857)
Timeframe: Cycle 2 Day 1 and Cycle 3 Day 1

Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs

Intervention	percentage of participants (Number)
	Physical Change: Cycle 2 Day 1: Very Much Worse	Physical Change: Cycle 2 Day 1: Moderately Worse	Physical Change: Cycle 2 Day 1: A Little Worse	Physical Change: Cycle 2 Day 1: No Change	Physical Change: Cycle 2 Day 1: A Little Better	Physical Change: Cycle 2 Day 1: Moderately Better	Physical Change: Cycle 2 Day 1: Very Much Better	Physical Change: Cycle 3 Day 1: Very Much Worse	Physical Change: Cycle 3 Day 1: Moderately Worse	Physical Change: Cycle 3 Day 1: A Little Worse	Physical Change: Cycle 3 Day 1: No Change	Physical Change: Cycle 3 Day 1: A Little Better	Physical Change: Cycle 3 Day 1: Moderately Better	Physical Change: Cycle 3 Day 1: Very Much Better	Appetite Change: Cycle 2 Day 1: Very Much Worse	Appetite Change: Cycle 2 Day 1: Moderately Worse	Appetite Change: Cycle 2 Day 1: A Little Worse	Appetite Change: Cycle 2 Day 1: No Change	Appetite Change: Cycle 2 Day 1: A Little Better	Appetite Change: Cycle 2 Day 1: Moderately Better	Appetite Change: Cycle 2 Day 1: Very Much Better	Appetite Change: Cycle 3 Day 1: Very Much Worse	Appetite Change: Cycle 3 Day 1: Moderately Worse	Appetite Change: Cycle 3 Day 1: A Little Worse	Appetite Change: Cycle 3 Day 1: No Change	Appetite Change: Cycle 3 Day 1: A Little Better	Appetite Change: Cycle 3 Day 1: Moderately Better	Appetite Change: Cycle 3 Day 1: Very Much Better	Pain Change: Cycle 2 Day 1: Very Much Worse	Pain Change: Cycle 2 Day 1: Moderately Worse	Pain Change: Cycle 2 Day 1: A Little Worse	Pain Change: Cycle 2 Day 1: No Change	Pain Change: Cycle 2 Day 1: A Little Better	Pain Change: Cycle 2 Day 1: Moderately Better	Pain Change: Cycle 2 Day 1: Very Much Better	Pain Change: Cycle 3 Day 1: Very Much Worse	Pain Change: Cycle 3 Day 1: Moderately Worse	Pain Change: Cycle 3 Day 1: A Little Worse	Pain Change: Cycle 3 Day 1: No Change	Pain Change: Cycle 3 Day 1: A Little Better	Pain Change: Cycle 3 Day 1: Moderately Better	Pain Change: Cycle 3 Day 1: Very Much Better
AG-120	1.5	4.5	22.4	38.8	22.4	9.0	1.5	2.0	5.9	3.9	41.2	29.4	15.7	2.0	1.5	4.5	20.9	50.7	13.4	7.5	1.5	0.0	5.9	5.9	64.7	11.8	7.8	3.9	0.0	9.0	9.0	64.2	7.5	10.4	0.0	0.0	3.9	11.8	60.8	7.8	11.8	3.9
Placebo	0.0	13.6	9.1	27.3	36.4	9.1	4.5	0.0	0.0	8.3	58.3	16.7	16.7	0.0	0.0	4.5	18.2	45.5	13.6	9.1	9.1	0.0	8.3	0.0	50.0	25.0	0.0	16.7	0.0	13.6	9.1	54.5	18.2	4.5	0.0	0.0	0.0	8.3	66.7	8.3	8.3	8.3

Clinically significant vital signs were recorded as adverse events; there were some vital signs reported as Grade 3 or higher adverse events. Grading categories were determined by NCI CTCAE, version 4.03. (NCT02989857)
Timeframe: From first dose of the study drug up to end of treatment visit for each intervention (Up to approximately 4 Years)

Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response

Intervention	percentage of participants (Number)
	Pyrexia	Weight Decreased	Hypertension	Hypotension
After Crossover to AG-120	2.3	0.0	7.0	2.3
AG-120	0.8	0.8	1.6	1.6
Placebo	0.0	1.7	1.7	1.7

The EQ-5D-5L assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Percentages are rounded off to whole number at the nearest decimal. (NCT02989857)
Timeframe: Cycle 3 Day 1

Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status

Intervention	percentage of participants (Number)
	Mobility: No Problems Walking	Mobility: Slight Problems Walking	Mobility: Moderate Problems Walking	Mobility: Severe Problems Walking	Mobility: Unable to Walk	Self-Care: No Problems Washing or Dressing	Self-Care: Slight Problems Washing or Dressing	Self-Care: Moderate Problems Washing or Dressing	Self-Care: Severe Problems Washing or Dressing	Usual Activities: No Problems Doing Usual Activities	Usual Activities: Slight Problems Doing Usual Activities	Usual Activities: Moderate Problems Doing Usual Activities	Usual Activities: Severe Problems Doing Usual Activities	Usual Activities: Unable to do Usual Activities	Pain/Discomfort: No Pain or Discomfort	Pain/Discomfort: Slight Pain or Discomfort	Pain/Discomfort: Moderate Pain or Discomfort	Pain/Discomfort: Severe Pain or Discomfort	Pain/Discomfort: Extreme Pain or Discomfort	Anxiety/Depression: Not Anxious or Depressed	Anxiety/Depression: Slightly Anxious or Depressed	Anxiety/Depression: Moderately Anxious or Depressed	Anxiety/Depression: Severely Anxious or Depressed
AG-120	52.0	28.0	16.0	4.0	0.0	88.0	8.0	2.0	2.0	42.0	34.0	16.0	8.0	0.0	40.0	42.0	10.0	6.0	2.0	50.0	44.0	6.0	0.0
Placebo	41.7	25.0	33.3	0.0	0.0	83.3	16.7	0.0	0.0	33.3	41.7	25.0	0.0	0.0	41.7	33.3	25.0	0.0	0.0	33.3	33.3	25.0	8.3

The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classified participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair. A higher score means a worse functional status. (NCT02989857)
Timeframe: Baseline

Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S)

Intervention	percentage of participants (Number)
	0	1	2	3	4
AG-120	39.7	59.5	0.0	0.8	0.0
Placebo	31.1	67.2	1.6	0.0	0.0

The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S was measured using the possible outcomes none, mild, moderate, severe, and very severe. Percentages are rounded off to whole number at the nearest decimal. (NCT02989857)
Timeframe: Cycle 2 Day 1 and Cycle 3 Day 1

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4

Intervention	percentage of participants (Number)
	Physical Decline: Cycle 2 Day 1: None	Physical Decline: Cycle 2 Day 1: Mild	Physical Decline: Cycle 2 Day 1: Moderate	Physical Decline: Cycle 2 Day 1: Severe	Physical Decline: Cycle 2 Day 1: Very Severe	Physical Decline: Cycle 3 Day 1: None	Physical Decline: Cycle 3 Day 1: Mild	Physical Decline: Cycle 3 Day 1: Moderate	Physical Decline: Cycle 3 Day 1: Severe	Physical Decline: Cycle 3 Day 1: very Severe	Appetite Decrease: Cycle 2 Day 1: None	Appetite Decrease: Cycle 2 Day 1: Mild	Appetite Decrease: Cycle 2 Day 1: Moderate	Appetite Decrease: Cycle 2 Day 1: Severe	Appetite Decrease: Cycle 2 Day 1: Very Severe	Appetite Decrease: Cycle 3 Day 1: None	Appetite Decrease: Cycle 3 Day 1: Mild	Appetite Decrease: Cycle 3 Day 1: Moderate	Appetite Decrease: Cycle 3 Day 1: Severe	Appetite Decrease: Cycle 3 Day 1: Very Severe	Pain Severity: Cycle 2 Day 1: None	Pain Severity: Cycle 2 Day 1: Mild	Pain Severity: Cycle 2 Day 1: Moderate	Pain Severity: Cycle 2 Day 1: Severe	Pain Severity: Cycle 2 Day 1: Very Severe	Pain Severity: Cycle 3 Day 1: None	Pain Severity: Cycle 3 Day 1: Mild	Pain Severity: Cycle 3 Day 1: Moderate	Pain Severity: Cycle 3 Day 1: Severe	Pain Severity: Cycle 3 Day 1: Very Severe
AG-120	55.2	23.9	16.4	3.0	1.5	70.6	11.8	15.7	2.0	0.0	53.7	32.8	10.4	1.5	1.5	70.6	15.7	7.8	5.9	0.0	32.8	38.8	23.9	4.5	0.0	39.2	35.3	17.6	7.8	0.0
Placebo	31.8	27.3	31.8	9.1	0.0	75.0	16.7	8.3	0.0	0.0	45.5	13.6	36.4	4.5	0.0	58.3	25.0	16.7	0.0	0.0	31.8	13.6	40.9	9.1	4.5	33.3	25.0	41.7	0.0	0.0

%BAUEC0-4 is the percent inhibition for AUEC0-4. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4

Intervention	percent (Mean)
	Cycle 1 Day 1	Cycle 2 Day 1
Randomization Phase AG-120 Plus Cross Over Phase AG-120	20.22090	74.9750

AUEC0-4 is the area of the response curve from time point zero (predose) up to 4 hr postdose. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value)

Intervention	h*ng/mL (Mean)
	Cycle 1 Day 1	Cycle 2 Day 1
Randomization Phase AG-120 Plus Cross Over Phase AG-120	3334.3	368.4

B is the Baseline Effect Value. Crossover C1D1 and crossover C2D1 visits were combined with C1D1 and C2D1 visits, respectively for the analysis of this endpoint. (NCT02989857)
Timeframe: Post-dose Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle = 28 days)

Time to Reach Maximal Plasma Concentration (Tmax) of AG-120

Intervention	ng/mL (Mean)
	Cycle 1 Day 1	Cycle 2 Day 1
Randomization Phase AG-120 Plus Cross Over Phase AG-120	1107.70	795.09

Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants

Intervention	hours (h) (Median)
	Cycle 1 Day 1	Cycle 2 Day 1
Randomization Phase AG-120 Plus Cross Over Phase AG-120	2.63	2.07

Combined Response Rate is the percentage of participants with Complete Response (CR), including stringent Complete Response (sCR), and Very Good Partial Response (VGPR) according to the International Myeloma Working Group (IMWG) criteria during the Induction Phase (Cycles 1-13, 28-day cycles). CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. (NCT02046070)
Timeframe: Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)

Duration of Response (DOR) in NDMM Participants

Intervention	percentage of participants (Number)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	27
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	24

DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the initiation of alternative therapy. (NCT02046070)
Timeframe: Up to 45 Months

Duration of Response (DOR) in RRMM Participants

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	32.2
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	36.6

DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the alternative therapy. (NCT02046070)
Timeframe: Up to 45 months

Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	26.3

ORR is the percentage of participants with CR, VGPR or PR according to IMWG criteria. CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PC) in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved free light chain (FLC) levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of each 28 day cycle (Up to 45 months)

Progression Free Survival (PFS) in NDMM Participants

Intervention	percentage of participants (Mean)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	49

PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death. (NCT02046070)
Timeframe: Up to 45 months

Progression Free Survival (PFS) in RRMM Participants

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	23.5
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	23.0

PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death. (NCT02046070)
Timeframe: Up to 45 months

Time to Progression (TTP) in NDMM Participants

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	14.2

TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression. (NCT02046070)
Timeframe: Up to 45 months

Time to Progression (TTP) in RRMM Participants

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	30.9
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	32.2

TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression. (NCT02046070)
Timeframe: Up to 45 months

Time to Response (TTR) in NDMM Participants During the Induction Phase

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	16.8

TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the initiation of alternative therapy in a participant who responded. (NCT02046070)
Timeframe: Up to 1 year

Time to Response (TTR) in RRMM Participants

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	2.2
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	1.9

TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the alternative therapy in a participant who responded. (NCT02046070)
Timeframe: Up to 45 months

AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants

Intervention	months (Median)
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	2.1

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants

Intervention	hr*ng/mL (Mean)
	Cycle 1 Day 1	Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	885.167	1338.333
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	792.600	1226.600

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants

Intervention	hr*ng/mL (Mean)
	Cycle 1 Day 1	Cycle 1 Day 15
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	518.167	1241.000

EORTC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement). (NCT02046070)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of End of Treatment (EOT) (Up to 45 months)

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants

Intervention	score on a scale (Mean)
	Global Health Status/QoL, Change from BL at EOT	Physical functioning, Change from BL at EOT	Role functioning, Change from BL at EOT	Emotional functioning, Change from BL at EOT	Cognitive functioning, Change from BL at EOT	Social functioning, Change from BL at EOT	Fatigue, Change from BL at EOT	Nausea/Vomiting, Change from BL at EOT	Pain, Change from BL at EOT	Dyspnea, Change from BL at EOT	Insomnia, Change from BL at EOT	Appetite Loss, Change from BL at EOT	Constipation, Change from BL at EOT	Diarrhea, Change from BL at EOT	Financial Difficulties, Change from BL at EOT
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	-5.50	-6.00	-7.67	-5.00	-5.33	-11.33	5.11	3.33	5.00	10.00	-6.00	4.67	2.00	6.00	4.00

EORTC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement). (NCT02046070)
Timeframe: Baseline (BL) (Day 1 of Cycle 1), Day 1 of Cycle 13 (Up to 1 year)

Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants

Intervention	score on a scale (Mean)
	Global Health Status/QoL, Change from BL; Cycle 13	Physical functioning, Change from BL at Cycle 13	Role functioning, Change from BL at Cycle 13	Emotional functioning, Change from BL at Cycle 13	Cognitive functioning, Change from BL at Cycle 13	Social functioning, Change from BL at Cycle 13	Fatigue, Change from BL at Cycle 13	Nausea/Vomiting, Change from BL at Cycle 13	Pain, Change from BL at Cycle 13	Dyspnea, Change from BL at Cycle 13	Insomnia, Change from BL at Cycle 13	Appetite Loss, Change from BL at Cycle 13	Constipation, Change from BL at Cycle 13	Diarrhea, Change from BL at Cycle 13	Financial Difficulties, Change from BL at Cycle 13
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	3.47	14.17	8.33	11.34	2.78	9.03	-10.88	-4.86	-13.89	-11.11	-16.67	-18.06	-13.89	-2.78	4.17
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	-5.43	17.97	6.52	2.54	-7.25	-11.59	-6.76	-4.35	-10.87	-7.25	-10.14	-7.25	-5.80	5.80	1.45

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants

"An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.~A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator." (NCT02046070)
Timeframe: First dose of study drug through 30 days after last dose of drug (Up to 45 months)

Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants

"An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment.~A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator." (NCT02046070)
Timeframe: First dose of study drug through 30 days after last dose of drug (Up to 45 months)

Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles

Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants

Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants

Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase

Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles

Percentage of participants with Overall Response (CR + VGPR + PR), CR, VGPR and PR according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component <100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or <200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. (NCT02046070)
Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants

(NCT02046070)
Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168) hours postdose

Progression Free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD), as evaluated by an independent review committee according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occured first. PD was defined as ≥25% increase from lowest value in: serum/urine M component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels must be >10 mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must have been ≥10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size increase; hypercalcemia development. (NCT02181413)
Timeframe: Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks until progression of disease or death (to data cutoff: approximately 4 years)

Intervention	Participants (Count of Participants)
	Any AE	Grade 3 or Higher AEs	AEs Resulting in Treatment Discontinuation	AEs Resulting in Dose Reduction	SAEs
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	35	27	9	11	17
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	34	27	11	10	20

Intervention	Participants (Count of Participants)
	Any AE	Grade 3 or Higher AE	AEs Resulting in Treatment Discontinuation	AEs Resulting in Dose Reduction	SAEs
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	72	49	19	30	30

Intervention	percentage of participants (Number)
	CR + VGPR	CR	VGPR	PR	SD	PD
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	19	5	14	44	37	10

Intervention	percentage of participants (Number)
	CR + VGPR + PR	CR + VGPR	CR	VGPR	PR	SD	PD
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	82	36	15	21	67	18	0
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	71	32	12	21	59	18	6

Article	Year
FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation. Clinical cancer research : an official journal of the American Association for Cancer Research, 2022, 07-01, Volume: 28, Issue:13 Topics: Abdominal Pain; Adult; Asthenia; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma;	2022
Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. The Lancet. Oncology, 2020, Volume: 21, Issue:6 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bile Duct Neoplasms; Cholangiocarcinoma; Dise	2020
A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia. Leukemia research, 2018, Volume: 64 Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Disease Progression; Dose-Response Relationship, Dru	2018
Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma. Journal of medical economics, 2018, Volume: 21, Issue:8 Topics: Absenteeism; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Boron C	2018
All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. European journal of cancer (Oxford, England : 1990), 2019, Volume: 106 Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Austr	2019
Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet (London, England), 2019, 01-19, Volume: 393, Issue:10168 Topics: Administration, Oral; Antineoplastic Agents; Boron Compounds; Disease Progression; Double-Blind Meth	2019
Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet (London, England), 2019, 01-19, Volume: 393, Issue:10168 Topics: Administration, Oral; Antineoplastic Agents; Boron Compounds; Disease Progression; Double-Blind Meth	2019
Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet (London, England), 2019, 01-19, Volume: 393, Issue:10168 Topics: Administration, Oral; Antineoplastic Agents; Boron Compounds; Disease Progression; Double-Blind Meth	2019
Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet (London, England), 2019, 01-19, Volume: 393, Issue:10168 Topics: Administration, Oral; Antineoplastic Agents; Boron Compounds; Disease Progression; Double-Blind Meth	2019
Phase I trial of the HSP90 inhibitor PF-04929113 (SNX5422) in adult patients with recurrent, refractory hematologic malignancies. Clinical lymphoma, myeloma & leukemia, 2013, Volume: 13, Issue:4 Topics: Adult; Aged; Aged, 80 and over; Benzamides; Cohort Studies; Disease Progression; Dose-Response Relat	2013
Phase I clinical trial of oral rigosertib in patients with myelodysplastic syndromes. British journal of haematology, 2013, Volume: 162, Issue:4 Topics: Administration, Oral; Aged; Aged, 80 and over; Biological Availability; Capsules; Disease Progressio	2013
Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study. Investigational new drugs, 2016, Volume: 34, Issue:3 Topics: Adult; Aged; Antineoplastic Agents; Area Under Curve; Boron Compounds; Disease Progression; Dose-Res	2016
Neurological deterioration in acute lacunar infarctions: the role of excitatory and inhibitory neurotransmitters. Stroke, 2001, Volume: 32, Issue:5 Topics: Acute Disease; Aged; Brain Infarction; Disease Progression; Female; gamma-Aminobutyric Acid; Glutami	2001

Article	Year
Altered bile acid glycine : taurine ratio in the progression of chronic liver disease. Journal of gastroenterology and hepatology, 2022, Volume: 37, Issue:1 Topics: Bile Acids and Salts; Case-Control Studies; Chronic Disease; Disease Progression; Female; Glycine; H	2022
Clinical course of COPD in patients with Arg16Gly (rs1042713) polymorphism of ADRB2 gene. Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace, 2022, Sep-13, Volume: 93, Issue:2 Topics: Arginine; Bronchodilator Agents; Disease Progression; Glycine; Humans; Polymorphism, Genetic; Pulmon	2022
Amino Acid Substitution within Seven-Octapeptide Repeat Insertions in the Prion Protein Gene Associated with Short-Term Course. Viruses, 2022, 10-13, Volume: 14, Issue:10 Topics: Amino Acid Substitution; Codon; Creutzfeldt-Jakob Syndrome; Curriculum; Disease Progression; Glutama	2022
Multiple BCL2 mutations cooccurring with Gly101Val emerge in chronic lymphocytic leukemia progression on venetoclax. Blood, 2020, 03-05, Volume: 135, Issue:10 Topics: Amino Acid Substitution; Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic; Cohort Stud	2020
Metabolic alterations in meningioma reflect the clinical course. BMC cancer, 2021, Mar-01, Volume: 21, Issue:1 Topics: Aged; Algorithms; Biomarkers, Tumor; Choline; Cluster Analysis; Disease Progression; Female; Glycine	2021
Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2020, Volume: 18, Issue:3 Topics: Carcinoma, Hepatocellular; Disease Progression; Glycine; Glyphosate; Humans; Liver; Liver Cirrhosis;	2020
Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice. Journal of hematology & oncology, 2019, 07-05, Volume: 12, Issue:1 Topics: Animals; Disease Progression; Female; Glycine; Glyphosate; Herbicides; Humans; Male; Mice; Mice, Inb	2019
Cerebral level of vGlut1 is increased and level of glycine is decreased in TgSwDI mice. Journal of Alzheimer's disease : JAD, 2014, Volume: 39, Issue:1 Topics: Aging; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Autoradiog	2014
[Anesthetic management of posterior lumbar spinal fusion in a patient suspected of having acute exacerbation of chronic interstitial pneumonia]. Masui. The Japanese journal of anesthesiology, 2014, Volume: 63, Issue:2 Topics: Acute-Phase Reaction; Aged; Airway Management; Anesthesia; Chronic Disease; Disease Progression; Eme	2014
Motor progression of Parkinson's disease with the leucine-rich repeat kinase 2 G2019S mutation. Movement disorders : official journal of the Movement Disorder Society, 2014, Volume: 29, Issue:8 Topics: Aged; Disease Progression; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Glyc	2014
Serum metabonomic analysis of apoE(-/-) mice reveals progression axes for atherosclerosis based on NMR spectroscopy. Molecular bioSystems, 2014, Volume: 10, Issue:12 Topics: Animals; Atherosclerosis; Biomarkers; Cholesterol, HDL; Cholesterol, LDL; Choline; Diet, High-Fat; D	2014
A woman with a rare p.Glu74Gly transthyretin mutation presenting exclusively with a rapidly progressive neuropathy: a case report. Journal of medical case reports, 2014, Dec-04, Volume: 8 Topics: Adult; Amyloid Neuropathies, Familial; Benzoxazoles; Disease Progression; Fatal Outcome; Female; Gen	2014
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. Journal of the American Heart Association, 2015, Dec-31, Volume: 5, Issue:1 Topics: Aged; Angina, Stable; Apolipoprotein A-I; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Corona	2015
Hydrogen sulphide exacerbates acute pancreatitis by over-activating autophagy via AMPK/mTOR pathway. Journal of cellular and molecular medicine, 2016, Volume: 20, Issue:12 Topics: Alkynes; AMP-Activated Protein Kinases; Animals; Autophagy; Cell Line; Disease Progression; Glycine;	2016
Collagen VI glycine mutations: perturbed assembly and a spectrum of clinical severity. Annals of neurology, 2008, Volume: 64, Issue:3 Topics: Amino Acid Sequence; Cells, Cultured; Collagen Diseases; Collagen Type VI; Connective Tissue; Diseas	2008
Beta2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. Chest, 2009, Volume: 135, Issue:5 Topics: Adolescent; Adrenergic beta-Agonists; Albuterol; Asthma; Child; Child, Preschool; Disease Progressio	2009
Progressive neuropathology and cognitive decline in a single Arctic APP transgenic mouse model. Neurobiology of aging, 2011, Volume: 32, Issue:2 Topics: Age Factors; Alanine; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Anim	2011
Ectodomain shedding of E-cadherin and c-Met is induced by Helicobacter pylori infection. Experimental cell research, 2009, Dec-10, Volume: 315, Issue:20 Topics: ADAM Proteins; ADAM10 Protein; Amyloid Precursor Protein Secretases; Cadherins; Cell Line; Disease P	2009
The proinflammatory action of microglial P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis. Journal of immunology (Baltimore, Md. : 1950), 2009, Oct-01, Volume: 183, Issue:7 Topics: Alanine; Amino Acid Substitution; Amyotrophic Lateral Sclerosis; Animals; Cell Line, Transformed; Ce	2009
Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes. Brain : a journal of neurology, 2010, Volume: 133, Issue:Pt 5 Topics: Arginine; Brain; Brain Diseases; Cerebellum; Cysteine; Diffuse Cerebral Sclerosis of Schilder; Diffu	2010
Relationship between neuropathology and disease progression in the SOD1(G93A) ALS mouse. Experimental neurology, 2011, Volume: 227, Issue:2 Topics: Alanine; Amino Acid Substitution; Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Di	2011
Retinal remodeling in the Tg P347L rabbit, a large-eye model of retinal degeneration. The Journal of comparative neurology, 2011, Oct-01, Volume: 519, Issue:14 Topics: Adult; Animals; Animals, Genetically Modified; Disease Models, Animal; Disease Progression; Electror	2011
Uneventful clinical courses of Korean patients with methylcrotonylglycinuria and their common mutations. Journal of human genetics, 2012, Volume: 57, Issue:1 Topics: Asian People; Carbon-Carbon Ligases; Child; Child, Preschool; Disease Progression; Female; Glycine;	2012
PGC-1α protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model. Muscle & nerve, 2011, Volume: 44, Issue:6 Topics: Alanine; Amino Acid Substitution; Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Di	2011
Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Molecular vision, 2012, Volume: 18 Topics: Administration, Oral; Aldehyde Reductase; Animals; Catalase; Cataract; Crystallins; Diabetes Mellitu	2012
CAG mutation effect on rate of progression in Huntington's disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2002, Volume: 23 Suppl 2 Topics: Age of Onset; Alanine; Cysteine; Disease Progression; DNA Mutational Analysis; Female; Follow-Up Stu	2002
Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. Journal of hematotherapy & stem cell research, 2003, Volume: 12, Issue:3 Topics: Alanine; Animals; Cord Blood Stem Cell Transplantation; Disease Models, Animal; Disease Progression;	2003
The relationship of plasma glutamine to ammonium and of glycine to acid-base balance in propionic acidaemia. Journal of inherited metabolic disease, 2003, Volume: 26, Issue:1 Topics: Acid-Base Equilibrium; Amino Acid Metabolism, Inborn Errors; Bicarbonates; Biomarkers; Diet, Protein	2003
A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump. Journal of hepatology, 2004, Volume: 40, Issue:1 Topics: Adenosine Triphosphatases; Amino Acid Sequence; Animals; Aspartic Acid; ATP Binding Cassette Transpo	2004
[Peculiarities of sporadic motor neuron disease associated with D90A and G12R mutations in Russian population]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2003, Volume: 103, Issue:11 Topics: Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Arginine; Copper; Disease Progression; Elect	2003
Poor outcome for neonatal-type nonketotic hyperglycinemia treated with high-dose sodium benzoate and dextromethorphan. Journal of child neurology, 2004, Volume: 19, Issue:1 Topics: Brain; Child, Preschool; Chromosome Aberrations; Dextromethorphan; Diazepam; Disease Progression; Di	2004
Modifier controls severity of a novel dominant low-frequency MyosinVIIA (MYO7A) auditory mutation. Journal of medical genetics, 2004, Volume: 41, Issue:5 Topics: Adult; Amino Acid Sequence; Amino Acid Substitution; Chromosome Mapping; Chromosomes, Human, Pair 11	2004
Reduced reactivation rate in mutant CuZnSOD and progression rate of amyotrophic lateral sclerosis. European journal of neurology, 2004, Volume: 11, Issue:6 Topics: Alanine; Amyotrophic Lateral Sclerosis; Bacteria; Blotting, Western; Cloning, Molecular; Copper; Dis	2004
The fibroblast growth factor receptor-4 Arg388 allele is associated with prostate cancer initiation and progression. Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Sep-15, Volume: 10, Issue:18 Pt 1 Topics: Alleles; Arginine; Case-Control Studies; Cell Movement; Collagen; Disease Progression; DNA; DNA, Com	2004
Natural history of nonketotic hyperglycinemia in 65 patients. Neurology, 2004, Nov-23, Volume: 63, Issue:10 Topics: Adolescent; Age of Onset; Agenesis of Corpus Callosum; Anticonvulsants; Apnea; Child; Child, Prescho	2004
Mild glycine encephalopathy (NKH) in a large kindred due to a silent exonic GLDC splice mutation. Neurology, 2005, Apr-26, Volume: 64, Issue:8 Topics: Adolescent; Alternative Splicing; Arabs; Brain; Brain Chemistry; Child; Child, Preschool; Disease Pr	2005
Impact of the Asp299Gly polymorphism in the toll-like receptor 4 (tlr-4) gene on disease course of multiple sclerosis. Journal of neuroimmunology, 2005, Volume: 165, Issue:1-2 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspartic Acid; Cells, Cultured; Cytokines; Disease Progr	2005
FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression. Cellular signalling, 2006, Volume: 18, Issue:6 Topics: Alleles; Amino Acid Substitution; Arginine; Breast Neoplasms; Cell Line; Cell Movement; Cells, Cultu	2006
Late-onset mitochondrial myopathy with dystrophic changes due to a G7497A mutation in the mitochondrial tRNA(Ser(UCN)) gene. Acta neuropathologica, 2005, Volume: 110, Issue:4 Topics: Adult; Alanine; Disease Progression; DNA Mutational Analysis; DNA, Mitochondrial; Family Health; Fem	2005
Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis. Journal of gastroenterology, 2006, Volume: 41, Issue:4 Topics: Adult; Animals; Biomarkers; Cells, Cultured; Colitis; Colitis, Ulcerative; Dextran Sulfate; Disease	2006
Progressive vacuolating glycine leukoencephalopathy with pulmonary hypertension. Annals of neurology, 2006, Volume: 60, Issue:1 Topics: Disease Progression; Fatal Outcome; Female; Glycine; Humans; Hyperglycemic Hyperosmolar Nonketotic C	2006
Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser substitution of PGC-1A and the Pro12Ala substitution of PPARG2 predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. Diabetes, 2006, Volume: 55, Issue:7 Topics: Amino Acid Substitution; Diabetes Mellitus, Type 2; Disease Progression; Female; Glucose Intolerance	2006
FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2006, Aug-10, Volume: 24, Issue:23 Topics: Adult; Aged; Alleles; Antineoplastic Combined Chemotherapy Protocols; Arginine; Biomarkers, Tumor; B	2006
Identification of a novel, putative cataract-causing allele in CRYAA (G98R) in an Indian family. Molecular vision, 2006, Jul-12, Volume: 12 Topics: Adult; alpha-Crystallin A Chain; Arginine; Asian People; Cataract; Disease Progression; Female; Gene	2006
Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 2006, Oct-24, Volume: 103, Issue:43 Topics: Aging; Amyotrophic Lateral Sclerosis; Animals; Animals, Newborn; Bone Marrow Cells; Bone Marrow Tran	2006
Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurology, 2006, Oct-24, Volume: 67, Issue:8 Topics: Aged; alpha-Synuclein; Brain; Cell Line; Disability Evaluation; Disease Progression; Female; Glycine	2006
Global distribution and reduced penetrance: Lrrk2 R1441C in an Irish Parkinson's disease kindred. Movement disorders : official journal of the Movement Disorder Society, 2007, Jan-15, Volume: 22, Issue:2 Topics: Arginine; Binding Sites; Disease Progression; Glycine; Histidine; Humans; Ireland; Leucine-Rich Repe	2007
VGLUT1 and GLYT2 labeling of sacrocaudal motoneurons in the spinal cord injured spastic rat. Experimental neurology, 2007, Volume: 204, Issue:1 Topics: Animals; Behavior, Animal; Disease Progression; Female; Glutamic Acid; Glycine; Glycine Plasma Membr	2007
The G51S purine nucleoside phosphorylase polymorphism is associated with cognitive decline in Alzheimer's disease patients. Human psychopharmacology, 2007, Volume: 22, Issue:2 Topics: Alleles; Alzheimer Disease; Apolipoprotein E4; Cognition Disorders; Disease Progression; Follow-Up S	2007
The dual peroxisome proliferator-activated receptor alpha/gamma activator muraglitazar prevents the natural progression of diabetes in db/db mice. The Journal of pharmacology and experimental therapeutics, 2007, Volume: 321, Issue:1 Topics: Animals; Body Weight; C-Peptide; Diabetes Mellitus, Experimental; Disease Progression; Fatty Acids,	2007
[Outcome of patients with acute exacerbation of idiopathic interstitial fibrosis (IPF) treated with sivelestat and the prognostic value of serum KL-6 and surfactant protein D]. Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society, 2007, Volume: 45, Issue:6 Topics: Acute Disease; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers; Chronic Disease; Disease Pro	2007
Sanfilippo syndrome type D: natural history and identification of 3 novel mutations in the GNS Gene. Archives of neurology, 2007, Volume: 64, Issue:11 Topics: Adolescent; Adult; Aspartic Acid; Disease Progression; DNA Mutational Analysis; Family Health; Femal	2007
Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis: the effect of riluzole treatment. Clinical neurology and neurosurgery, 2008, Volume: 110, Issue:3 Topics: Aged; Amyotrophic Lateral Sclerosis; Chromatography, High Pressure Liquid; Disease Progression; Fema	2008
Neonatal nonketotic hyperglycinemia. Indian journal of pediatrics, 2007, Volume: 74, Issue:12 Topics: Amino Acid Metabolism, Inborn Errors; Disease Progression; Fatal Outcome; Glycine; Humans; Hyperglyc	2007
Variation in the biochemical/biophysical properties of mutant superoxide dismutase 1 enzymes and the rate of disease progression in familial amyotrophic lateral sclerosis kindreds. Human molecular genetics, 1999, Volume: 8, Issue:8 Topics: Amino Acid Substitution; Amyotrophic Lateral Sclerosis; Animals; Centrifugation; Copper; COS Cells;	1999
Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters. American journal of respiratory and critical care medicine, 2000, Volume: 161, Issue:6 Topics: Animals; Bronchoalveolar Lavage Fluid; Cricetinae; Disease Progression; Endotoxins; Glycine; Leukocy	2000
Retinal degeneration in the nervous mutant mouse. IV. Inner retinal changes. Experimental eye research, 2001, Volume: 72, Issue:3 Topics: Animals; Apoptosis; Cell Count; Disease Progression; Electroretinography; gamma-Aminobutyric Acid; G	2001
K-ras mutational analysis of polyclonal colorectal cancers identifies uniclonal circulating tumor cells. The American surgeon, 2001, Volume: 67, Issue:8 Topics: Aspartic Acid; Colorectal Neoplasms; Disease Progression; DNA Mutational Analysis; Genes, ras; Glyci	2001
Multiple panel of biomarkers for TIA/stroke evaluation. Stroke, 2002, Volume: 33, Issue:5 Topics: Adult; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Autoantibodies; Biomarkers; Diagno	2002

glycine and Disease Exacerbation

Research Excerpts

Research

Studies (74)

Authors

Clinical Trials (17)

Trial Overview

Trial Outcomes

Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)

Accumulation Ratio Based on Cmax (Racc Cmax)

Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)

Change From Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score

DOR as Assessed by the IRC Per RECIST v1.1

Duration of Response (DOR) as Assessed by the Investigator

Objective Response Rate (ORR) as Assessed by the Investigator RECIST Version 1.1

ORR as Assessed by the IRC Per RECIST v1.1

Overall Survival (OS)

Percentage of Participants Who Required At Least One Concomitant Medications During the Treatment

PFS as Determined by Investigator

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BRtrough

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: Rtrough

Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)

Time to Response (TTR) as Assessed by the Investigator

TTR as Assessed by the IRC Per RECIST v1.1

Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)

Change From Baseline in Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 Subscales Scores

Change From Baseline in HRQOL Based on: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)

Maximum Observed Plasma Concentration (Cmax) of AG-120

Percentage of Participants Who Experienced Laboratory Abnormalities Reported as Grade 3 or Higher Adverse Events

Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes Reported as Adverse Events

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Percentage of Participants With Change Based on HRQOL: Patient Global Impression of Change (PGI-C)

Percentage of Participants With Clinically Significant Grade 3 or Higher Vital Signs AEs

Percentage of Participants With Each EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Dimension Response

Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status

Percentage of Participants With Severity Based on HRQOL: Patient Global Impression of Severity (PGI-S)

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: %BAUEC0-4

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: AUEC0-4

Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120: B (Baseline Effect Value)

Time to Reach Maximal Plasma Concentration (Tmax) of AG-120

Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants

Duration of Response (DOR) in NDMM Participants

Duration of Response (DOR) in RRMM Participants

Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants

Progression Free Survival (PFS) in NDMM Participants

Progression Free Survival (PFS) in RRMM Participants

Time to Progression (TTP) in NDMM Participants

Time to Progression (TTP) in RRMM Participants

Time to Response (TTR) in NDMM Participants During the Induction Phase

Time to Response (TTR) in RRMM Participants

AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants

AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants

Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants

Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants

Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants

Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants

Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants

Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles

Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants

Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants

Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase

Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles

Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants

Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants

Progression Free Survival (PFS)

Reviews

Trials

Other Studies