NCT02651688

A Multi-Center Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Body Composition and Metabolic Parameters With Diet and Exercise in Conjunction With Treatment With 12.5 mg or 25 mg Enclomiphene

Completed Phase 2 Results posted Last updated 27 June 2019

What this trial tests

Phase 2 trial testing Placebo in Acquired Hypogonadotropic Hypogonadism in 50 participants. Completed in 2 May 2017.

Timeline

11 January 2016

Primary endpoint
2 May 2017

2 May 2017

Quick facts

Lead sponsor	Repros Therapeutics Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	50
Start date	11 January 2016
Primary completion	2 May 2017
Estimated completion	2 May 2017
Sites	5 locations across United States

Drugs / interventions tested

• Placebo
• Enclomiphene — full drug profile →

Conditions studied

• Acquired Hypogonadotropic Hypogonadism — all drugs for Acquired Hypogonadotropic Hypogonadism →
• Obesity — all drugs for Obesity →

Sponsor

Repros Therapeutics Inc. — full company profile →

Who can join

Adults 18 to 60, male only, with Acquired Hypogonadotropic Hypogonadism or Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Lean Body Mass (LBM) at Week 48 Primary · Baseline (Day 0) to Week 48

LBM was assessed using dual-energy X-ray absorptiometry (DXA). A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	65.23	± 7.08
Enclomiphene 25 mg	65.60	± 7.88
Placebo	68.12	± 7.43

Change from Baseline to week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	3.14	± 4.03
Enclomiphene 25 mg	2.40	± 3.54
Placebo	1.05	± 4.10

Change From Baseline in Body Strength (Chest Press Weight) at Week 48 Primary · Baseline (Day 0) to Week 48

Body strength was assessed from maximum chest and leg press weight achieved, using an inclined plane leg press and vertical chest press. A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	169.00	± 56.46
Enclomiphene 25 mg	180.93	± 95.43
Placebo	151.50	± 63.68

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	75.00	± 28.80
Enclomiphene 25 mg	76.90	± 51.55
Placebo	87.27	± 50.61

Change From Baseline in Body Strength (Leg Press Weight) at Week 48 Primary · Baseline (Day 0) to Week 48

Body strength was assessed from maximum chest and leg press weight achieved, using an inclined plane leg press and vertical chest press. A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	466.06	± 291.7
Enclomiphene 25 mg	464.20	± 288.2
Placebo	580.86	± 264.2

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	406.92	± 222.2
Enclomiphene 25 mg	323.80	± 200.3
Placebo	351.50	± 216.2

Change From Baseline in Blood Luteinizing Hormone (LH) Level at Week 48 Primary · Baseline (Day 0) to Week 48

A blood sample was collected at Baseline and Week 48 for the assessment of the hormone parameter LH measured in milli-International Units per milliliter (mIU/mL). A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	3.93	± 1.82
Enclomiphene 25 mg	3.41	± 0.93
Placebo	3.51	± 1.31

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	2.40	± 3.39
Enclomiphene 25 mg	3.01	± 4.70
Placebo	0.83	± 1.25

Change From Baseline in Blood Testosterone (T) Level at Week 48 Primary · Baseline (Day 0) to Week 48

A blood sample was collected at Baseline and Week 48 for the assessment of the hormone parameter T. A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	243.56	± 55.03
Enclomiphene 25 mg	218.24	± 43.39
Placebo	223.53	± 58.01

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	173.81	± 130.7
Enclomiphene 25 mg	237.17	± 181.4
Placebo	43.33	± 59.50

Change From Baseline in Blood Dihydrotestosterone (DHT) Level at Week 48 Primary · Baseline (Day 0) to Week 48

A blood sample was collected at Baseline and Week 48 for the assessment of the hormone parameter DHT. A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	18.78	± 7.74
Enclomiphene 25 mg	16.06	± 5.76
Placebo	15.73	± 5.92

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	15.13	± 12.92
Enclomiphene 25 mg	20.75	± 15.21
Placebo	4.25	± 5.96

Change From Baseline in Blood Estradiol (E2) Level at Week 48 Primary · Baseline (Day 0) to Week 48

A blood sample was collected at Baseline and Week 48 for the assessment of the hormone parameter E2. A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	50.04	± 16.80
Enclomiphene 25 mg	48.43	± 15.15
Placebo	45.49	± 12.05

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	-3.00	± 28.02
Enclomiphene 25 mg	13.03	± 26.20
Placebo	-11.46	± 15.41

Change From Baseline in Ratio of Testosterone: Estradiol (T:E2) at Week 48 Primary · Baseline (Day 0) to Week 48

The T:E2 ratio was calculated as the value of T/value of E2 using the same units. A positive change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	5.26	± 1.73
Enclomiphene 25 mg	4.93	± 1.96
Placebo	5.21	± 1.88

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	5.11	± 7.57
Enclomiphene 25 mg	2.89	± 3.09
Placebo	2.85	± 3.36

Change From Baseline in Ratio of Dihydrotestosterone: Testosterone (DHT:T) at Week 48 Primary · Baseline (Day 0) to Week 48

The DHT:T ratio was calculated as the value of DHT/value of T using the same units. A negative change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	0.08	± 0.02
Enclomiphene 25 mg	0.08	± 0.03
Placebo	0.07	± 0.03

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	0.01	± 0.03
Enclomiphene 25 mg	0.00	± 0.02
Placebo	0.00	± 0.02

Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 48 Primary · Baseline (Day 0) to Week 48

A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter HbA1c. A negative change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	5.56	± 0.35
Enclomiphene 25 mg	5.95	± 0.74
Placebo	5.77	± 0.32

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	-0.34	± 0.37
Enclomiphene 25 mg	-0.54	± 0.27
Placebo	-0.65	± 0.28

Change From Baseline in Blood Glucose Level at Week 48 Primary · Baseline (Day 0) to Week 48

A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter Glucose. A negative change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	98.39	± 14.71
Enclomiphene 25 mg	101.41	± 10.69
Placebo	97.93	± 13.22

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	-1.81	± 16.69
Enclomiphene 25 mg	-5.25	± 8.70
Placebo	-4.33	± 13.29

Change From Baseline in Blood C-reactive Protein (CRP) Level at Week 48 Primary · Baseline (Day 0) to Week 48

A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter CRP. A negative change from Baseline indicates improvement.

Baseline

Group	Value	95% CI
Enclomiphene 12.5 mg	0.25	± 0.22
Enclomiphene 25 mg	0.35	± 0.41
Placebo	0.35	± 0.35

Change from Baseline to Week 48

Group	Value	95% CI
Enclomiphene 12.5 mg	0.06	± 0.50
Enclomiphene 25 mg	-0.05	± 0.29
Placebo	-0.15	± 0.25

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of the study drug through 30 days of the treatment end date (approximately 13 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Enclomiphene 12.5 mg

Serious: 2/18 (11%)

Deaths: 0/18

Enclomiphene 25 mg

Serious: 0/17 (0%)

Deaths: 0/17

Placebo

Serious: 0/15 (0%)

Deaths: 0/15

Serious adverse events (2 terms)

Reaction	System	Enclomiphene 12.5 mg	Enclomiphene 25 mg	Placebo
Acute myocardial infarction	Cardiac disorders	—	—	—
Ischaemic stroke	Vascular disorders	—	—	—

Other adverse events (50 terms — click to expand)

Reaction	System	Enclomiphene 12.5 mg	Enclomiphene 25 mg	Placebo
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Gastroenteritis viral	Infections and infestations	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Ventricular extrasystoles	Cardiac disorders	—	—	—
Abdominal hernia	Gastrointestinal disorders	—	—	—
Umbilical hernia	Gastrointestinal disorders	—	—	—
Epigastric discomfort	Gastrointestinal disorders	—	—	—
Gingival bleeding	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Toothache	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Chest discomfort	General disorders	—	—	—
Night sweats	General disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Coxsackie viral infection	Infections and infestations	—	—	—
Influenza	Infections and infestations	—	—	—
Viral pharyngitis	Infections and infestations	—	—	—
Bronchitis	Infections and infestations	—	—	—
Food poisoning	Infections and infestations	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—	—
Wrist fracture	Injury, poisoning and procedural complications	—	—	—
Joint injury	Injury, poisoning and procedural complications	—	—	—
Soft tissue injury	Injury, poisoning and procedural complications	—	—	—
Electrocardiogram abnormal	Investigations	—	—	—
Haematocrit increased	Investigations	—	—	—
Heart rate increased	Investigations	—	—	—
Bursitis	Musculoskeletal and connective tissue disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Tendonitis	Musculoskeletal and connective tissue disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Exostosis	Musculoskeletal and connective tissue disorders	—	—	—
Ligament sprain	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Seizure	Nervous system disorders	—	—	—
Anxiety	Psychiatric disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Irritability	Psychiatric disorders	—	—	—

Most-reported serious reactions: Acute myocardial infarction, Ischaemic stroke.

Data from ClinicalTrials.gov NCT02651688 adverse events section.

Sponsor's own description

The purpose of this study is to compare the effects of 12 months of treatment with enclomiphene 12.5 mg, 25 mg, or placebo capsules on body composition and metabolic parameters in overweight men with acquired hypogonadotropic hypogonadism \[confirmed morning testosterone (T) ≤300 ng/dL\] following a 6 month diet and 15 month exercise program.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.