Page last updated: 2024-11-12

acyline

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID16137348
CHEMBL ID262747
MeSH IDM0283540

Synonyms (12)

Synonym
d-alaninamide, n-acetyl-3-(2-naphthalenyl)-d-alanyl-4-chloro-d-phenylalanyl-3-(3-pyridinyl)-d-alanyl-l-seryl-4-(acetylamino)-l-phenylalanyl-4-(acetylamino)-d-phenylalanyl-l-leucyl-n6-(1-methylethyl)-l-lysyl-l-prolyl-
acyline
CHEMBL262747 ,
mer-104
bdbm50102456
ac-d-nal-[d-(pcl)phe]-d-pal-ser-[aph(ac)]-d-[aph(ac)]-leu-ilys-pro-dala-nh2
s3439d3b35 ,
unii-s3439d3b35
DB11906
Q27288520
CS-0006118
HY-16027

Research Excerpts

Overview

Acyline is an effective GnRH antagonist inducing acute castration in all subjects. It reliably inhibits gonadotropins and testosterone (T) levels in men for 48 h after a single dose up to 75 microg/kg.

ExcerptReferenceRelevance
"Acyline is an effective GnRH antagonist inducing acute castration in all subjects."( Impact of acute biochemical castration on insulin sensitivity in healthy adult men.
Andersen, DK; Caronia, LM; Dwyer, AA; Elahi, D; Hayes, FJ; Rabiee, A; Thomas, B; Torriani, M; Yialamas, MA, 2010
)
1.08
"Acyline is a novel GnRH antagonist that reliably inhibits gonadotropins and testosterone (T) levels in men for 48 h after a single dose up to 75 microg/kg. "( A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men.
Amory, JK; Anawalt, BD; Bremner, WJ; Coviello, AD; Herbst, KL; Page, S, 2004
)
2
"Acyline is a novel GnRH antagonist found in animal studies to be a potent suppressor of circulating gonadotropin and testosterone (T) levels. "( Acyline: the first study in humans of a potent, new gonadotropin-releasing hormone antagonist.
Amory, JK; Anawalt, BD; Bremner, WJ; Herbst, KL, 2002
)
3.2

Effects

ExcerptReferenceRelevance
"Acyline contraception has been described in cats, but few data are available on the drug's long-term effect on growth. "( Evaluation of Long-Term Effects of the Gonadotrophin-Releasing-Hormone Antagonist Acyline on Domestic-Cat Growth.
Faya, M; Furlan, P; Gobello, C; Marchetti, C; Priotto, M; Rodríguez, M; Romero, MG,
)
1.8

Treatment

Acyline-treated stallions failed to respond with a rise in FSH, LH, and testosterone after exogenous GnRH stimulation (gonadorelin) at Day 46 of treatment. Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH.

ExcerptReferenceRelevance
"Acyline treatment resulted in cessation of follicle growth on Day 3 with smaller (P < 0.0001) maximum follicle diameter in Trio carriers (6.6 ± 0.2 mm) than noncarriers (8.7 ± 0.4 mm)."( Selection of fewer dominant follicles in Trio carriers given GnRH antagonist and luteinizing hormone action replaced by nonpulsatile human chorionic gonadotropin†.
Andrade, JP; García-Guerra, A; Ginther, OJ; Gomez-León, VE; Kirkpatrick, BW; Moghbeli, SM; Wiltbank, MC, 2020
)
1.28
"Acyline-treated stallions failed to respond with a rise in FSH, LH, and testosterone after exogenous GnRH stimulation (gonadorelin) at Day 46 of treatment compared to pretreatment stimulation and control stallions."( Reversible downregulation of the hypothalamic-pituitary-gonadal axis in stallions with a novel GnRH antagonist.
Ball, BA; Canisso, IF; Claes, AN; Davolli, GM; Esteller-Vico, A; Fedorka, CE; Squires, EL; Troedsson, MH; Woodward, EM, 2016
)
1.16
"Acyline treatment on day 10 resulted in an immediate decrease in FSH, without a significant effect on day of emergence of a new wave or growth of follicles from 7 to 11 mm on days 11-13."( Effect of suppression of FSH with a GnRH antagonist (acyline) before and during follicle deviation in the mare.
Beg, MA; Checura, CM; Gastal, EL; Gastal, MO; Ginther, OJ; Parrish, JJ; Wiltbank, MC, 2009
)
1.32
"Acyline treatment significantly reduced testis weights, serum androgens, LH and FSH, and adluminal germ cells (pachytene spermatocyte, round and elongating spermatids)."( Gonadotropins regulate rat testicular tight junctions in vivo.
McCabe, MJ; Meachem, SJ; Robertson, DM; Smooker, PM; Stanton, PG; Tarulli, GA, 2010
)
1.08
"Acyline treatment reduced the number of hemorrhagic cysts and the number of Sertoli-like filled cords within ArKO ovaries."( The lack of estrogen and excess luteinizing hormone are responsible for the female ArKO mouse phenotype.
Drummond, AE; Findlay, JK; Jones, ME; Liew, SH, 2010
)
1.08
"Acyline treatment caused a significant (P<0.05) decline in P levels (2.9+/-0.5 vs 0.5+/-0.3 ng/ml, 0 vs 48 h post-treatment) and premature menstruation compared with untreated controls (P<0.05)."( Characteristics and regulation of the ovarian cycle in vervet monkeys (Chlorocebus aethiops).
Fanton, JW; Hess, DL; Maginnis, GM; Molskness, TA; Stouffer, RL; Wright, JW, 2007
)
1.06

Pharmacokinetics

ExcerptReferenceRelevance
"We enrolled eight healthy young men in a pharmacokinetic and pharmacodynamic study of 10, 20 and 40 mg doses of GIPET-enhanced oral acyline."( Oral administration of the GnRH antagonist acyline, in a GIPET-enhanced tablet form, acutely suppresses serum testosterone in normal men: single-dose pharmacokinetics and pharmacodynamics.
Amory, JK; Bremner, WJ; Leonard, TW; McKenna, MJ; O'Toole, E; Page, ST, 2009
)
0.82
" We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study."( Pharmacokinetics of modified slow-release oral testosterone over 9 days in normal men with experimental hypogonadism.
Amory, JK; Bremner, WJ; Bush, MA; Caricofe, RB; Clark, RV; Lee, A; Page, ST; Roth, MY; Rubinow, K; Zhi, H,
)
0.13

Bioavailability

ExcerptReferenceRelevance
" The use of a proprietary enhancer system called GIPET, which is based on medium-chain fatty acids, facilitates the oral bioavailability of peptides."( Oral administration of the GnRH antagonist acyline, in a GIPET-enhanced tablet form, acutely suppresses serum testosterone in normal men: single-dose pharmacokinetics and pharmacodynamics.
Amory, JK; Bremner, WJ; Leonard, TW; McKenna, MJ; O'Toole, E; Page, ST, 2009
)
0.62

Dosage Studied

ExcerptRelevanceReference
" We hypothesized that GIPET enhancement would allow for the safe oral dosing of acyline for the treatment of prostate cancer."( Oral administration of the GnRH antagonist acyline, in a GIPET-enhanced tablet form, acutely suppresses serum testosterone in normal men: single-dose pharmacokinetics and pharmacodynamics.
Amory, JK; Bremner, WJ; Leonard, TW; McKenna, MJ; O'Toole, E; Page, ST, 2009
)
0.84
" Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG."( Pharmacokinetics of modified slow-release oral testosterone over 9 days in normal men with experimental hypogonadism.
Amory, JK; Bremner, WJ; Bush, MA; Caricofe, RB; Clark, RV; Lee, A; Page, ST; Roth, MY; Rubinow, K; Zhi, H,
)
0.13
"Serum sex steroid concentrations may alter body composition and glucose homoeostasis in men in a dose-response manner."( Dose-response effects of sex hormone concentrations on body composition and adipokines in medically castrated healthy men administered graded doses of testosterone gel.
Amory, JK; Cooper, LA; Marck, BT; Matsumoto, AM; Page, ST; Rubinow, KB; Thirumalai, A, 2017
)
0.46
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gonadotropin-releasing hormone receptorHomo sapiens (human)IC50 (µMol)0.00220.00010.12895.2000AID266056; AID286263; AID74279
Gonadotropin-releasing hormone receptorRattus norvegicus (Norway rat)IC50 (µMol)0.00150.00030.15422.0000AID286264
Mu-type opioid receptorCavia porcellus (domestic guinea pig)IC50 (µMol)0.00050.00020.660310.0000AID286263
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gonadotropin-releasing hormone receptorHomo sapiens (human)Kd0.00250.00010.00090.0025AID74429
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (4)

Processvia Protein(s)Taxonomy
gonadotropin secretionGonadotropin-releasing hormone receptorHomo sapiens (human)
cellular response to gonadotropin-releasing hormoneGonadotropin-releasing hormone receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayGonadotropin-releasing hormone receptorHomo sapiens (human)
cellular response to hormone stimulusGonadotropin-releasing hormone receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (2)

Processvia Protein(s)Taxonomy
peptide bindingGonadotropin-releasing hormone receptorHomo sapiens (human)
gonadotropin-releasing hormone receptor activityGonadotropin-releasing hormone receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
plasma membraneGonadotropin-releasing hormone receptorHomo sapiens (human)
membraneGonadotropin-releasing hormone receptorHomo sapiens (human)
plasma membraneGonadotropin-releasing hormone receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (16)

Assay IDTitleYearJournalArticle
AID286266Antagonist activity at human GnRHR expressed in COS7 cells assessed as inhibition of GnRH-stimulated inositol phosphate production after 2 hrs2007Journal of medicinal chemistry, May-03, Volume: 50, Issue:9
Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives.
AID286264Antagonist activity at rat GnRHR expressed in HEK293 cells assessed as inhibition of GnRH-induced luciferase response by reporter gene assay2007Journal of medicinal chemistry, May-03, Volume: 50, Issue:9
Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives.
AID104506Compound was tested for inhibition of Leutenizing hormone release at 72 hours (long duration) in castrated male rat assay2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID286269Inhibition of plasma testosterone levels in Sprague-Dawley rat at 19.6 uM, sc by enzyme-linked immunosorbent assay2007Journal of medicinal chemistry, May-03, Volume: 50, Issue:9
Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives.
AID286267Solubility in 5% mannitol2007Journal of medicinal chemistry, May-03, Volume: 50, Issue:9
Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives.
AID195410Compound was tested for histamine release at a concentration of 300 ug/mL2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID195409Compound was tested for histamine release at a concentration of 30 ug/mL2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID266056Antagonist activity at human GnRH receptor expressed in HEK293 cells as inhibition of GnRH-induced LH secretion by reporter gene assay2006Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12
Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.
AID74429Competitive antagonism of GnRH-induced response in the reporter gene assay2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID286263Antagonist activity at human GnRHR expressed in HEK293 cells assessed as inhibition of GnRH-induced luciferase response by reporter gene assay2007Journal of medicinal chemistry, May-03, Volume: 50, Issue:9
Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives.
AID266062Histamine release in mast cells by ELISA2006Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12
Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.
AID286265Ratio of IC50 for rat GnRHR to IC50 for human GnRHR in HEK293 cells2007Journal of medicinal chemistry, May-03, Volume: 50, Issue:9
Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives.
AID195401Effective dose for histamine release was determined2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID74279Antagonism of human GnHR receptor, determined in a reporter gene assay in HEK293 cells2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID195406Compound was tested for histamine release at a concentration of 100 ug/mL2001Journal of medicinal chemistry, Feb-01, Volume: 44, Issue:3
GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6.
AID266063Antiovulatory activity in rat at 2 ug, sc2006Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12
Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus. Part III.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (72)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's1 (1.39)18.2507
2000's26 (36.11)29.6817
2010's41 (56.94)24.3611
2020's4 (5.56)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 35.18

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index35.18 (24.57)
Research Supply Index4.66 (2.92)
Research Growth Index6.40 (4.65)
Search Engine Demand Index45.20 (26.88)
Search Engine Supply Index2.06 (0.95)

This Compound (35.18)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials28 (36.36%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other49 (63.64%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (15)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Mechanisms of Hormonal Control of Spermatogenesis in Man [NCT02147964]Phase 20 participants (Actual)Interventional2019-06-30Withdrawn(stopped due to No funding was obtained for this study.)
Hormonal Regulation of Circulating Endothelial Progenitor Cells and HDL-C in Men Title Changed With New Protocol (12/14/09): Hormonal Regulation of HDL-C in Men [NCT00729859]Phase 231 participants (Actual)Interventional2008-12-31Completed
Oral Administration of the GnRH Antagonist Acyline in Normal Men [NCT00471185]Phase 19 participants (Actual)Interventional2007-06-30Completed
Male Hormonal Contraception Development: Suppression of Spermatogenesis With the Addition of a Potent GnRH Antagonist (Acyline) to Testosterone and DMPA (ACY-5) -Sub-Study (HOP 5) [NCT00156650]Phase 1/Phase 223 participants (Actual)Interventional2004-12-31Completed
Manipulation of the Intratesticular Hormonal Milieu With Exogenous Testosterone (Short Title (HOP-3) [NCT00839319]Phase 1/Phase 259 participants (Actual)Interventional2009-03-31Completed
Male Hormonal Contraceptive Development: Suppression of Spermatogenesis With the Addition of a Potent Antagonist (Acyline) to Testosterone and DMPA (ACY-5) [NCT00161447]Phase 1/Phase 243 participants (Actual)Interventional2004-05-31Completed
Oral Administration of the GnRH Antagonist Acyline in Normal Men Part II: Multiple-dose Pharmacokinetics (Acyline-7/MER 104-02) [NCT00603187]Phase 1/Phase 24 participants (Actual)Interventional2008-01-31Completed
Effect of Varying Testosterone Levels on Insulin Sensitivity in Normal and IHH Men [NCT00470990]40 participants (Anticipated)Interventional2002-10-31Completed
The Effects of Testosterone on Prostate Tissue in Normal Men (ACYP-1) [NCT00161486]Phase 113 participants (Actual)Interventional2004-07-31Completed
Dose Response Effects of Exogenous Testosterone on the Prostate and Comparison With Effects on Body Composition (Short Title: PROS-2) [NCT01327495]Phase 2/Phase 362 participants (Actual)Interventional2011-10-31Completed
Oral Androgens in Man-6: Pharmacokinetics of Slow and Fast Release, External Matrix Oral Testosterone Formulations in Normal Men With Experimental Hypogonadism [NCT00663793]Phase 116 participants (Actual)Interventional2008-10-31Completed
Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men [NCT01686828]Phase 1/Phase 253 participants (Actual)Interventional2013-06-30Completed
Pharmacokinetics of Modified Slow-Release Oral Testosterone Over 10 Days in Normal Men With Experimental Hypogonadism [NCT01167829]Phase 114 participants (Actual)Interventional2010-07-31Completed
Mechanisms of Control of the Intratesticular Hormonal Milieu in Man [NCT01215292]Phase 1/Phase 246 participants (Actual)Interventional2011-01-31Completed
Cardiovascular Consequences of Hypogonadism in Men [NCT02758431]379 participants (Anticipated)Interventional2016-07-01Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00603187 (3) [back to overview]FSH Blood Serum Concentration
NCT00603187 (3) [back to overview]LH Blood Serum Concentration
NCT00603187 (3) [back to overview]Testosterone Blood Serum Concentration
NCT00663793 (3) [back to overview]Area Under the Curve-serum DHT
NCT00663793 (3) [back to overview]Area Under the Curve-Serum T
NCT00663793 (3) [back to overview]Area Under the Curve-E2
NCT00729859 (10) [back to overview]Endothelial Progenitor Cells
NCT00729859 (10) [back to overview]Estradiol Concentration
NCT00729859 (10) [back to overview]Fasting Lipid Levels
NCT00729859 (10) [back to overview]Fasting Serum Insulin
NCT00729859 (10) [back to overview]Follicle Stimulating Hormone (FSH)
NCT00729859 (10) [back to overview]Homeostasis Model of Insulin Resistance (HOMA-IR)
NCT00729859 (10) [back to overview]Luteinizing Hormone Concentration (LH)
NCT00729859 (10) [back to overview]Quantitative Insulin Sensitivity Check Index (QUICKI)
NCT00729859 (10) [back to overview]Sex Hormone Binding Globulin (SHBG)
NCT00729859 (10) [back to overview]Testosterone Concentration
NCT00839319 (4) [back to overview]Intratesticular Testosterone (ITT-T)
NCT00839319 (4) [back to overview]Serum Follicle Stimulating Hormone (FSH)
NCT00839319 (4) [back to overview]Serum Luteinizing Hormone (LH)
NCT00839319 (4) [back to overview]Serum Testosterone (T)
NCT01167829 (10) [back to overview]Maximum Sex Hormone-Binding Globulin (SHGB)Concentration
NCT01167829 (10) [back to overview]Maximum Testosterone Concentration
NCT01167829 (10) [back to overview]Mean Estradiol Concentration
NCT01167829 (10) [back to overview]Mean SHGB Concentration
NCT01167829 (10) [back to overview]Mean Testosterone Concentration
NCT01167829 (10) [back to overview]Mean Dihydrotestosterone (DHT) Concentration
NCT01167829 (10) [back to overview]Free T Maximum Concentration
NCT01167829 (10) [back to overview]Free Testosterone Mean Concentration
NCT01167829 (10) [back to overview]Maximum Dihydrotestosterone (DHT) Concentration
NCT01167829 (10) [back to overview]Maximum Estradiol Concentration
NCT01215292 (3) [back to overview]Intratesticular Androstenedione (ADD) Level
NCT01215292 (3) [back to overview]Intratesticular Dihydrotestosterone (DHT) Level
NCT01215292 (3) [back to overview]Intratesticular Testosterone (IT-T) Level
NCT01327495 (14) [back to overview]17-OHP
NCT01327495 (14) [back to overview]17-OHPreg
NCT01327495 (14) [back to overview]Androsterone
NCT01327495 (14) [back to overview]DHEA
NCT01327495 (14) [back to overview]Dihydrotestosterone (DHT)
NCT01327495 (14) [back to overview]Prostate Specific Antigen
NCT01327495 (14) [back to overview]Prostate Tissue DHT Concentrations After Treatment
NCT01327495 (14) [back to overview]Prostate Tissue Testosterone Concentrations After Treatment
NCT01327495 (14) [back to overview]Prostate Volume
NCT01327495 (14) [back to overview]Serum Testosterone
NCT01327495 (14) [back to overview]Progesterone
NCT01327495 (14) [back to overview]Androstenedione
NCT01327495 (14) [back to overview]Pregnenolone
NCT01327495 (14) [back to overview]International Prostate Symptom Score (IPSS)
NCT01686828 (3) [back to overview]Insulin Sensitivity Quantified by Matsuda Index
NCT01686828 (3) [back to overview]Changes in Body Composition
NCT01686828 (3) [back to overview]Changes in Adipose Tissue Gene Expression

FSH Blood Serum Concentration

Blood for measurement of serum follicle stimulating hormone concentrations was obtained prior to the 1st, 5th and 6th dose of GIPET™-enhanced oral acyline and 0.5,1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 60 hours after the 7th dose. (NCT00603187)
Timeframe: 7 days

Interventioniu/L (Mean)
pre-dose 1pre-dose 5pre-dose 6pre-dose 7dose 7, 0.5 hoursdose 7, 1 hourdose 7, 1.5 hoursdose 7, 2 hoursdose 7, 3 hoursdose 7, 4 hoursdose 7, 6 hoursdose 7, 8 hoursdose 7, 12 hoursdose 7, 24 hoursdose 7, 36 hoursdose 7, 48 hoursdose 7, 60 hoursRecovery/day 14
Oral Acyline2.802.052.332.232.482.382.452.452.332.202.051.932.032.282.483.002.933.20

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LH Blood Serum Concentration

Blood for measurement of serum leutenizing hormone concentrations was obtained prior to the 1st, 5th and 6th dose of GIPET™-enhanced oral acyline and 0.5,1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 60 hours after the 7th dose. (NCT00603187)
Timeframe: 7 days

Interventioniu/L (Mean)
pre-dose 1pre-dose 5pre-dose 6pre-dose 7dose 7, 0.5 hoursdose 7, 1 hourdose 7, 1.5 hoursdose 7, 2 hoursdose 7, 3 hoursdose 7, 4 hoursdose 7, 6 hoursdose 7, 8 hoursdose 7, 12 hoursdose 7, 24 hoursdose 7, 36 hoursdose 7, 48 hoursdose 7, 60 hoursRecovery/day 14
Oral Acyline4.872.734.784.155.805.185.305.403.832.982.351.942.404.106.707.205.808.10

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Testosterone Blood Serum Concentration

Blood for measurement of serum testosterone was obtained prior to the 1st, 5th and 6th dose of GIPET™-enhanced oral acyline and 0.5,1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 60 hours after the 7th dose. (NCT00603187)
Timeframe: 7 days

Interventionng/dl (Mean)
pre-dose 1pre-dose 5pre-dose 6pre-dose 7dose 7, 0.5 hoursdose 7, 1 hourdose 7, 1.5 hoursdose 7, 2 hoursdose 7, 3 hoursdose 7, 4 hoursdose 7, 6 hoursdose 7, 8 hoursdose 7, 12 hoursdose 7, 24 hoursdose 7, 36 hoursdose 7, 48 hoursdose 7, 60 hoursRecovery/day 14
Oral Acyline14.258.539.839.8310.109.5010.3310.659.808.787.086.806.889.308.2010.8310.1016.5

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Area Under the Curve-serum DHT

(NCT00663793)
Timeframe: 14-days

,
Interventionnmol*h/L (Mean)
external matrix 'immediate' releaseexternal matrix 'fast' releaseexternal matrix 'slow' release
Testosterone Only364239
Testosterone Plus Finasteride232626

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Area Under the Curve-Serum T

(NCT00663793)
Timeframe: 14 days

,
Interventionnmol*h/L (Mean)
external matrix 'immediate' releaseexternal matrix 'fast' releaseexternal matrix 'slow' release
Testosterone Only143144162
Testosterone Plus Finasteride198384237

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Area Under the Curve-E2

(NCT00663793)
Timeframe: 14 Days

,
Interventionnmol*h/L (Mean)
external matrix 'immediate' releaseexternal matrix 'fast' releaseexternal matrix 'slow' release
Testosterone Only181219611944
Testosterone Plus Finasteride224120023129

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Endothelial Progenitor Cells

Number of CD33 + CD134+ cells as a percentage of all lymphocytes (NCT00729859)
Timeframe: Baseline, Day 28

Interventionpercentage of all lymphocytes (Mean)
BaselineDay 28
Group 1: Acyline + Placebo Gel + Placebo Pill0.1010.081

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Estradiol Concentration

(NCT00729859)
Timeframe: Baseline, Day 28

,,
Interventionpmol/L (Mean)
BaselineDay 28
Group 1: Acyline + Placebo Gel, Placebo Pill95.431.9
Group 2: Acyline, Testosterone Gel117.8109.0
Group 3: Acyline, Testosterone Gel, Anastrozole Pill96.336.5

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Fasting Lipid Levels

(NCT00729859)
Timeframe: Baseline, Day 28, Day 56

,,
Interventionmmol/L (Mean)
Total cholesterol Day 0Total cholesterol Day 28Total cholesterol Day 56LDL choesterol Day 0LDL cholesterol Day 28LDL cholesterol Day 56HDL cholesterol Day 0HDL cholesterol Day 28HDL cholesterol Day 56Triglycerides Day 0Triglycerides Day 28Triglycerides Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill4.975.444.952.953.292.871.191.371.191.791.731.89
Group 2: Acyline, Testosterone Gel, Placebo Pill4.484.514.142.772.802.491.321.321.320.820.860.80
Group 3: Acyline, Testosterone Gel, Oral Anastrozole4.564.564.272.672.752.511.401.321.301.081.081.02

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Fasting Serum Insulin

(NCT00729859)
Timeframe: Baseline, Day 28, Day 56

,,
Interventionpicomolar (Mean)
BaselineDay 28Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill546954
Group 2: Acyline, Testosterone Gel, Placebo Pill655964
Group 3: Acyline, Testosterone Gel, Oral Anastrozole504250

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Follicle Stimulating Hormone (FSH)

(NCT00729859)
Timeframe: Baseline, 28 days

,,
InterventionIU/L (Mean)
BaselineDay 28
Group 1: Acyline + Placebo Gel, Placebo Pill4.20.42
Group 2: Acyline, Testosterone Gel2.90.39
Group 3: Acyline, Testosterone Gel, Anastrazole Pill2.50.87

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Homeostasis Model of Insulin Resistance (HOMA-IR)

HOMA IR is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher HOMA IR numbers are associated with increased insulin resistance and decreased insulin sensitivity. (NCT00729859)
Timeframe: Baseline, Day 28, Day 56

,,
InterventionHOMA score (Mean)
BaselineDay 28Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill1.82.42.2
Group 2: Acyline, Testosterone Gel, Placebo Pill2.01.91.9
Group 3: Acyline, Testosterone Gel, Oral Anastrozole1.61.41.7

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Luteinizing Hormone Concentration (LH)

(NCT00729859)
Timeframe: Baseline, Day 28

,,
InterventionIU/L (Mean)
BaselineDay 28
Group 1: Acyline + Placebo Gel, Placebo Pill4.30.31
Group 2: Acyline, Testosterone Gel4.70.69
Group 3: Acyline, Testosterone Gel, Anastrozole4.41.55

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Quantitative Insulin Sensitivity Check Index (QUICKI)

QUICKI is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher QUICKI are associated with decreased insulin resistance and increased insulin sensitivity. (NCT00729859)
Timeframe: Baseline, Day 28, Day 56

,,
InterventionQUICKI index (Mean)
BaselineDay 28Day 56
Group 1: Acyline + Placebo Gel, Placebo Pill0.360.340.35
Group 2: Acyline, Testosterone Gel, Placebo Pill0.350.350.35
Group 3: Acyline, Testosterone Gel, Oral Anastrozole0.360.380.36

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Sex Hormone Binding Globulin (SHBG)

(NCT00729859)
Timeframe: Baseline, Day 28

,,
Interventionnmol/L (Mean)
BaselineDay 28
Group 1: Acyline + Placebo Gel, Placebo Pill34.937.5
Group 2: Acyline, Testosterone Gel23.022.1
Group 3: Acyline, Testosterone Gel, Anastrozole Pill27.625.1

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Testosterone Concentration

(NCT00729859)
Timeframe: Baseline, Day 28

,,
Interventionnmol/L (Mean)
Baseline testosterone concentrationDay 28 testosterone concentration
Group 1: Acyline + Placebo Gel, Placebo Pill15.40.8
Group 2: Acyline, Testosterone Gel16.317.8
Group 3: Acyline, Testosterone Gel, Anastrozole16.519.0

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Intratesticular Testosterone (ITT-T)

(NCT00839319)
Timeframe: 10 days

InterventionIU/L (Median)
Acyline Plus Placebo77
Acyline Plus 15 IU hCG136
Acyline Plus 60 IU hCG319
Acyline Plus 125 IU hCG987
Acyline Plus Testosterone Gel73

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Serum Follicle Stimulating Hormone (FSH)

(NCT00839319)
Timeframe: 10 days

InterventionIU/L (Median)
Acyline Plus Placebo0.41
Acyline Plus 15 IU hCG0.41
Acyline Plus 60 IU hCG0.29
Acyline Plus 125 IU hCG0.28
Acyline Plus Testosterone Gel0.21

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Serum Luteinizing Hormone (LH)

(NCT00839319)
Timeframe: 10 days

InterventionIU/L (Median)
Acyline Plus Placebo0.13
Acyline Plus 15 IU hCG0.28
Acyline Plus 60 IU hCG0.49
Acyline Plus 125 IU hCG0.39
Acyline Plus Testosterone Gel0.14

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Serum Testosterone (T)

(NCT00839319)
Timeframe: 10 days

Interventionnmol/liter (Median)
Acyline Plus Placebo0.43
Acyline Plus 15 IU hCG1.5
Acyline Plus 60 IU hCG3.7
Acyline Plus 125 IU hCG8.4
Acyline Plus Testosterone Gel16

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Maximum Sex Hormone-Binding Globulin (SHGB)Concentration

(NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
300 mg Oral Testosterone3122

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Maximum Testosterone Concentration

initial pharmacokinetics [PK] (day 1) of oral testosterone dosed 3 times daily and the PK after 9 days of treatment (NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
Acyline and 300 mg Oral Testosterone924741

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Mean Estradiol Concentration

(NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
300 mg Oral Testosterone117

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Mean SHGB Concentration

(NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
300 mg Oral Testosterone2719

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Mean Testosterone Concentration

initial 24-hour pharmacokinetics (PK) of oral testosterone dosed 3 times daily and post 24-hour PK after 9 days of treatment (NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
Acyine and 300 mg Oral Testosterone378315

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Mean Dihydrotestosterone (DHT) Concentration

(NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
Acyline and 300 mg Oral Testosterone9669

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Free T Maximum Concentration

Free T normal range 4.7-18 ng/dL (NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1-2Day 9-10
300 mg Oral Testosterone2421

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Free Testosterone Mean Concentration

Free T normal range 4.7-18 ng/dL (NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1-2Day 9-10
300 mg Oral Testosterone8.78.3

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Maximum Dihydrotestosterone (DHT) Concentration

(NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
300 mg Oral Testosterone233142

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Maximum Estradiol Concentration

(NCT01167829)
Timeframe: baseline & day 9

Interventionng/dL (Geometric Mean)
Day 1Day 9
300 mg Oral Testosterone149

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Intratesticular Androstenedione (ADD) Level

(NCT01215292)
Timeframe: 10 days

Interventionng/mL (Median)
Acyline + Testosterone Gel (Tgel)+ Placebo.87
Acyline + Tgel + Ketoconazole 400mg0.5
Acyline + Tgel + Ketoconazole 800mg0.12
Acyline & TGel & Dutasteride 2.5mg1.7
Acyline & TGel & Anastrazole 1mg3.6

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Intratesticular Dihydrotestosterone (DHT) Level

(NCT01215292)
Timeframe: 10 days

Interventionng/mL (Median)
Acyline + Testosterone Gel (Tgel)+ Placebo3.17
Acyline & TGel & Ketoconazole 400 mg2.08
Acyline & TGel & Ketoconazole 800 mg1.46
Acyline & TGel & Dutasteride0.12
Acyline & TGel & Anastrazole3.63

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Intratesticular Testosterone (IT-T) Level

(NCT01215292)
Timeframe: 10 days

Interventionng/mL (Median)
Acyline + Testosterone Gel + Placebo14
Acyline + Tgel + Ketoconazole 400mg3.7
Acyline + Tgel + Ketoconazole 800mg1.7
Acyline & TGel & Dutasteride 2.5mg18.4
Acyline & TGel & Anastrazole 1mg24.0

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17-OHP

(NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 10.05
Arm 20.05
Arm 30.05
Arm 40.05
Arm 50.05
Arm 60.05

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17-OHPreg

(NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 11.19
Arm 21.25
Arm 31.23
Arm 41.05
Arm 51.02
Arm 61.36

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Androsterone

(NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 10.17
Arm 20.15
Arm 30.12
Arm 40.17
Arm 50.17
Arm 60.21

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DHEA

(NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 129.3
Arm 226.2
Arm 322.1
Arm 426.8
Arm 524.4
Arm 618.6

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Dihydrotestosterone (DHT)

(NCT01327495)
Timeframe: 12 weeks

Interventionng/mL (Median)
Arm 1/Placebo Acyline Inject & Placebo Testosterone Gel0.3
Arm 2 Acyline Inject Every 2 Weeks & Daily T 1% Gel 1.25g0.6
Arm 3 Acyline Inject Every 2 Weeks & Daily T 1% Gel 2.50.9
Acyline Inject Every 2 Weeks & Daily T 1% Gel 5g1.0
Acyline Inject Every 2 Weeks & Daily T 1% Gel 10g1.5
Acyline Inject Every 2 Weeks & Daily T 1% Gel 15g1.8

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Prostate Specific Antigen

(NCT01327495)
Timeframe: 12 weeks

Interventionng/dL (Median)
Arm 10.82
Arm 20.48
Arm 30.61
Arm 40.58
Arm 50.52
Arm 60.76

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Prostate Tissue DHT Concentrations After Treatment

To measure intraprostatic dihydrotestosterone [DHT] levels (NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 1/Placebo Acyline Inject & Placebo Testosterone Gel4.05
Arm 2 Acyline Inject Every 2 Weeks & Daily T 1% Gel 1.25g4.26
Arm 3 Acyline Inject Every 2 Weeks & Daily T 1% Gel 2.52.99
Acyline Inject Every 2 Weeks & Daily T 1% Gel 5g3.88
Acyline Inject Every 2 Weeks & Daily T 1% Gel 10g4.12
Acyline Inject Every 2 Weeks & Daily T 1% Gel 15g5.11

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Prostate Tissue Testosterone Concentrations After Treatment

To measure intraprostatic testosterone levels (NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 1/Placebo Acyline Inject & Placebo Testosterone Gel0.3
Arm 2 Acyline Inject Every 2 Weeks & Daily T 1% Gel 1.25g0.13
Arm 3 Acyline Inject Every 2 Weeks & Daily T 1% Gel 2.50.125
Acyline Inject Every 2 Weeks & Daily T 1% Gel 5g0.18
Acyline Inject Every 2 Weeks & Daily T 1% Gel 10g0.195
Acyline Inject Every 2 Weeks & Daily T 1% Gel 15g0.3

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Prostate Volume

(NCT01327495)
Timeframe: 12 weeks

Interventioncm^3 (Median)
Arm 119
Arm 218
Arm 319
Arm 415
Arm 516
Arm 620

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Serum Testosterone

(NCT01327495)
Timeframe: 12 weeks

Interventionng/mL (Median)
Arm 1/Placebo Acyline Inject & Placebo Testosterone Gel4.6
Arm 2 Acyline Inject Every 2 Weeks & Daily T 1% Gel 1.25g1.9
Arm 3 Acyline Inject Every 2 Weeks & Daily T 1% Gel 2.53.4
Acyline Inject Every 2 Weeks & Daily T 1% Gel 5g3.5
Acyline Inject Every 2 Weeks & Daily T 1% Gel 10g6.1
Acyline Inject Every 2 Weeks & Daily T 1% Gel 15g7.7

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Progesterone

(NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 10.09
Arm 20.08
Arm 30.06
Arm 40.08
Arm 50.09
Arm 60.07

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Androstenedione

(NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 10.16
Arm 20.11
Arm 30.12
Arm 40.13
Arm 50.18
Arm 60.14

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Pregnenolone

(NCT01327495)
Timeframe: 12 weeks

Interventionng/g (Median)
Arm 128.7
Arm 229.5
Arm 332.7
Arm 432.4
Arm 527.9
Arm 623.9

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International Prostate Symptom Score (IPSS)

IPSS score: 0-7 mildly symptomatic, 8-19 moderately symptomatic, 20-35 severely symptomatic (NCT01327495)
Timeframe: 12 weeks

Interventionunits on a scale (Median)
Arm 11
Arm 22
Arm 32.5
Arm 40
Arm 52.5
Arm 64

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Insulin Sensitivity Quantified by Matsuda Index

Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG*FI)*(FPG+PG30*2+PG60*2+PG90*2+PG120)/8*(FPI+PI30*2+PI60*2+PI90*2+PI)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60,90, and 120 minutes after oral glucose load; PI30,60,90, and 120=plasma insulin levels sampled at 30,60,90, and 120 minutes after the oral glucose load (NCT01686828)
Timeframe: 4 weeks

Interventionunits on a scale (Median)
Acyline & Placebo Gel & Placebo Pill5.0
Acyline & Testosterone Gel 1.25g/d & Placebo Pill9.4
Acyline & Testosterone Gel 5g/d & Placebo Pill7.2
Acyline & Testosterone Gel & Letrozole7.3

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Changes in Body Composition

Fat mass and lean mass were measured by dual energy X-ray absorptiometry (DEXA) at baseline and at the end of the 4 week treatment period (NCT01686828)
Timeframe: 4 weeks

,,,
Interventionkg (Mean)
Change in fat massChange in lean mass
Acyline & Placebo Gel & Placebo Pill1.1-1.2
Acyline & Testosterone Gel & Letrozole0.5-0.3
Acyline & Testosterone Gel 1.25g/d & Placebo Pill0.7-1.4
Acyline & Testosterone Gel 5g/d & Placebo Pill-0.40.0

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Changes in Adipose Tissue Gene Expression

We examined whether differences in lipoprotein lipase expression would be evident across study treatment groups. RNA was isolated from whole adipose tissue gene expression, and complementary DNA (cDNA) was synthesized from 1.5 ug of RNA per sample. Gene expression was measured by polymerase chain reaction (PCR) using predesigned TaqMan® Gene Expression Assays. Standard curves were included on each plate, so Ct values were converted to copy numbers of the target gene. Expression values were normalized to the geometric mean of the housekeeping genes phosphoglycerate kinase and 18s. (NCT01686828)
Timeframe: 4 weeks

Interventiongene copy number per ng RNA (Mean)
Acyline + Placebo Gel + Placebo Pills7493
Acyline + Testosterone Gel (1.25g/d) + Placebo Pills8224
Acyline + Testosterone Gel (5g/d) + Placebo Pills7885
Acyline + Testosterone Gel (5g/d) + Letrozole8320

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