Back to resultsA 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
Primary Purpose
Acquired Hypogonadotropic Hypogonadism, Obesity
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Enclomiphene
Sponsored by
About this trial
This is an interventional treatment trial for Acquired Hypogonadotropic Hypogonadism
Eligibility Criteria
Inclusion Criteria:
- Overweight (Body Mass Index (BMI) 30 to 42 (kg/m^2) inclusive) males age 18 to 60 inclusive.
- Waist circumference ≥ 40 inches (101.6 cm).
- Previously or concurrently diagnosed as having secondary hypogonadism.
- Must have 2 morning testosterone assessments at Visit 1, collected before 10 AM, 2-4 days apart, and both of which must be ≤ 300 (ng/dL).
- Luteinizing hormone (LH) >1.4 and < 9.4 milli International units per milliliter (mIU/mL) (at Visit 1 only).
- Glycated hemoglobin A1c (HbA1c) ≤7.5.
- Stable weight for last 3 months (+/- 10 pounds).
- Participant lives or works within 10 miles of the gym that will be used for the study.
- Must be fit enough to participate in the fitness program.
- Ability to complete the study in compliance with the protocol requirements.
- Ability to understand and provide written informed consent.
Exclusion Criteria:
- Any use of testosterone products (injectable, pelleted, transdermal or sublingual) in the 6 months prior to the study or any prior use of testosterone products for 12 months or longer at any time.
- Use of testosterone, Clomid, 5α-reductase inhibitors, human chorionic gonadotropin (hCG), androgen, estrogen, anabolic steroid, dehydroepiandrosterone (DHEA), or herbal hormone products during the study.
- Use of Clomid in the past year.
- Known hypersensitivity to Clomid.
- Allergy to soy, peanuts or latex.
- Chronic use of glucocorticoids (chronic use of inhaled or topical glucocorticoids is acceptable).
- History of drug abuse or chronic narcotic use including methadone.
- A recent history of alcoholism or illegal substance or steroid abuse (<2 years) or presence of moderate alcohol use (>21 drinks per week).
- Use of an investigational drug or product, or participation in a drug or medical device research study within 30 days prior to receiving study medication.
- A hematocrit >54%.
- Presence or known history of hyperprolactinemia with or without a tumor (prolactin >20 ng/mL).
- Current or history of prostate cancer or a suspicion of prostate disease unless ruled out by prostate biopsy, or a prostate specific antigen (PSA)>3.6.
- Current or history of breast cancer.
- Uncontrolled hypertension based on the Investigator's assessment at screening.
- History of bulimia nervosa or binge eating.
- Participant has (had) a lap band or undergone gastric bypass surgery.
- Participant has celiac disease or gluten intolerance.
- Participant has Type I diabetes.
- Participant has any condition which in the opinion of the investigator would interfere with the participant's ability to provide informed consent, comply with study instructions, possibly confound interpretation of study results, or endanger the participant if he took part in the study.
- Enrolled and randomized (if applicable) in a previous enclomiphene study.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Enclomiphene 12.5 mg
Enclomiphene 25 mg
Placebo
Arm Description
Enclomiphene 12.5 milligram (mg) capsule daily in the morning with approximately 8 ounces of water for up to 12 months. Participant followed a commercial diet plan and exercised with a personal trainer at least 3 times a week.
Enclomiphene 25 mg capsule daily in the morning with approximately 8 ounces of water for up to 12 months. Participant followed a commercial diet plan and exercised with a personal trainer at least 3 times a week.
One matching placebo capsule daily in the morning with approximately 8 ounces of water for up to 12 months. Participant followed a commercial diet plan and exercised with a personal trainer at least 3 times a week.
Outcomes
Primary Outcome Measures
Change From Baseline in Lean Body Mass (LBM) at Week 48
LBM was assessed using dual-energy X-ray absorptiometry (DXA). A positive change from Baseline indicates improvement.
Change From Baseline in Body Strength (Chest Press Weight) at 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.
Change From Baseline in Body Strength (Leg Press Weight) at 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.
Change From Baseline in Blood Luteinizing Hormone (LH) Level at 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.
Change From Baseline in Blood Testosterone (T) Level at 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.
Change From Baseline in Blood Dihydrotestosterone (DHT) Level at 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.
Change From Baseline in Blood Estradiol (E2) Level at 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.
Change From Baseline in Ratio of Testosterone: Estradiol (T:E2) at 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.
Change From Baseline in Ratio of Dihydrotestosterone: Testosterone (DHT:T) at 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.
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at 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.
Change From Baseline in Blood Glucose Level at 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.
Change From Baseline in Blood C-reactive Protein (CRP) Level at 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.
Change From Baseline in Blood Interleukin-6 (IL-6) Level at Week 48
A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter IL-6. A negative change from Baseline indicates improvement.
Change From Baseline in Blood Tumor Necrosis Factor Alpha (TNF-α) Level at Week 48
A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter TNF-α . A negative change from Baseline indicates improvement.
Change From Baseline in Blood Leptin Level at Week 48
A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter leptin. A negative change from Baseline indicates improvement.
Change From Baseline in Homeostatic Model of Assessment - Insulin Resistance (HOMA-IR) at Week 48
The HOMA-IR is the product of the blood Glucose and Insulin levels, divided by a constant. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/mL) × fasting plasma glucose (mmol/L)/22.5. A negative change from Baseline indicates improvement.
Change From Baseline in Blood Quantose-Insulin Resistance (IR) Score at Week 48
Quantose-IR is a laboratory-developed test that assesses insulin resistance. Quantose-IR score is based on a linear regression algorithm utilizing the quantitative measures (natural log transformed) of alpha-hydroxybutyrate, oleate, linoleoylglycerophosphocholine and insulin and was designed to estimate the natural log of insulin-induced glucose infusion rate normalized by whole body mass. The algorithm score is converted to the Quantose-IR score within a range of 1-120 by an arithmetic calculation where higher scores denote greater insulin resistance. A negative change from Baseline indicates improvement.
Change From Baseline in Body Mass Index (BMI) at Week 48
BMI is calculated as weight (kg)/height(cm^2). A negative change from Baseline indicates improvement.
Change From Baseline in Waist Circumference at Week 48
A negative change from Baseline indicates improvement.
Change From Baseline in Weight at Week 48
A negative change from Baseline indicates improvement.
Secondary Outcome Measures
Full Information
NCT ID
NCT02651688
First Posted
January 7, 2016
Last Updated
June 18, 2019
Sponsor
Repros Therapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02651688
Brief Title
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
Official Title
A Randomized, Double Blind, Placebo-Controlled, 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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
January 11, 2016 (Actual)
Primary Completion Date
May 2, 2017 (Actual)
Study Completion Date
May 2, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Repros Therapeutics Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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 T≤300 ng/dL) following a 6 month diet and 15 month exercise program. Participants must not have been treated with testosterone products in the 6 months prior to the study and must not ever have used testosterone products for a year or longer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acquired Hypogonadotropic Hypogonadism, Obesity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Enclomiphene 12.5 mg
Arm Type
Experimental
Arm Description
Enclomiphene 12.5 milligram (mg) capsule daily in the morning with approximately 8 ounces of water for up to 12 months. Participant followed a commercial diet plan and exercised with a personal trainer at least 3 times a week.
Arm Title
Enclomiphene 25 mg
Arm Type
Experimental
Arm Description
Enclomiphene 25 mg capsule daily in the morning with approximately 8 ounces of water for up to 12 months. Participant followed a commercial diet plan and exercised with a personal trainer at least 3 times a week.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One matching placebo capsule daily in the morning with approximately 8 ounces of water for up to 12 months. Participant followed a commercial diet plan and exercised with a personal trainer at least 3 times a week.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
One matching placebo capsule daily in the morning with approximately 8 ounces of water for up to 12 months.
Intervention Type
Drug
Intervention Name(s)
Enclomiphene
Intervention Description
Enclomiphene capsule daily in the morning with approximately 8 ounces of water for up to 12 months.
Primary Outcome Measure Information:
Title
Change From Baseline in Lean Body Mass (LBM) at Week 48
Description
LBM was assessed using dual-energy X-ray absorptiometry (DXA). A positive change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Body Strength (Chest Press Weight) at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Body Strength (Leg Press Weight) at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Luteinizing Hormone (LH) Level at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Testosterone (T) Level at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Dihydrotestosterone (DHT) Level at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Estradiol (E2) Level at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Ratio of Testosterone: Estradiol (T:E2) at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Ratio of Dihydrotestosterone: Testosterone (DHT:T) at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Glucose Level at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood C-reactive Protein (CRP) Level at Week 48
Description
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.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Interleukin-6 (IL-6) Level at Week 48
Description
A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter IL-6. A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Tumor Necrosis Factor Alpha (TNF-α) Level at Week 48
Description
A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter TNF-α . A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Leptin Level at Week 48
Description
A blood sample was collected at Baseline and Week 48 for the assessment of the metabolic parameter leptin. A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Homeostatic Model of Assessment - Insulin Resistance (HOMA-IR) at Week 48
Description
The HOMA-IR is the product of the blood Glucose and Insulin levels, divided by a constant. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/mL) × fasting plasma glucose (mmol/L)/22.5. A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Blood Quantose-Insulin Resistance (IR) Score at Week 48
Description
Quantose-IR is a laboratory-developed test that assesses insulin resistance. Quantose-IR score is based on a linear regression algorithm utilizing the quantitative measures (natural log transformed) of alpha-hydroxybutyrate, oleate, linoleoylglycerophosphocholine and insulin and was designed to estimate the natural log of insulin-induced glucose infusion rate normalized by whole body mass. The algorithm score is converted to the Quantose-IR score within a range of 1-120 by an arithmetic calculation where higher scores denote greater insulin resistance. A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Body Mass Index (BMI) at Week 48
Description
BMI is calculated as weight (kg)/height(cm^2). A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Waist Circumference at Week 48
Description
A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
Title
Change From Baseline in Weight at Week 48
Description
A negative change from Baseline indicates improvement.
Time Frame
Baseline (Day 0) to Week 48
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Overweight (Body Mass Index (BMI) 30 to 42 (kg/m^2) inclusive) males age 18 to 60 inclusive.
Waist circumference ≥ 40 inches (101.6 cm).
Previously or concurrently diagnosed as having secondary hypogonadism.
Must have 2 morning testosterone assessments at Visit 1, collected before 10 AM, 2-4 days apart, and both of which must be ≤ 300 (ng/dL).
Luteinizing hormone (LH) >1.4 and < 9.4 milli International units per milliliter (mIU/mL) (at Visit 1 only).
Glycated hemoglobin A1c (HbA1c) ≤7.5.
Stable weight for last 3 months (+/- 10 pounds).
Participant lives or works within 10 miles of the gym that will be used for the study.
Must be fit enough to participate in the fitness program.
Ability to complete the study in compliance with the protocol requirements.
Ability to understand and provide written informed consent.
Exclusion Criteria:
Any use of testosterone products (injectable, pelleted, transdermal or sublingual) in the 6 months prior to the study or any prior use of testosterone products for 12 months or longer at any time.
Use of testosterone, Clomid, 5α-reductase inhibitors, human chorionic gonadotropin (hCG), androgen, estrogen, anabolic steroid, dehydroepiandrosterone (DHEA), or herbal hormone products during the study.
Use of Clomid in the past year.
Known hypersensitivity to Clomid.
Allergy to soy, peanuts or latex.
Chronic use of glucocorticoids (chronic use of inhaled or topical glucocorticoids is acceptable).
History of drug abuse or chronic narcotic use including methadone.
A recent history of alcoholism or illegal substance or steroid abuse (<2 years) or presence of moderate alcohol use (>21 drinks per week).
Use of an investigational drug or product, or participation in a drug or medical device research study within 30 days prior to receiving study medication.
A hematocrit >54%.
Presence or known history of hyperprolactinemia with or without a tumor (prolactin >20 ng/mL).
Current or history of prostate cancer or a suspicion of prostate disease unless ruled out by prostate biopsy, or a prostate specific antigen (PSA)>3.6.
Current or history of breast cancer.
Uncontrolled hypertension based on the Investigator's assessment at screening.
History of bulimia nervosa or binge eating.
Participant has (had) a lap band or undergone gastric bypass surgery.
Participant has celiac disease or gluten intolerance.
Participant has Type I diabetes.
Participant has any condition which in the opinion of the investigator would interfere with the participant's ability to provide informed consent, comply with study instructions, possibly confound interpretation of study results, or endanger the participant if he took part in the study.
Enrolled and randomized (if applicable) in a previous enclomiphene study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Chan
Organizational Affiliation
Allergan
Official's Role
Study Director
Facility Information:
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
City
Garden City
State/Province
New York
ZIP/Postal Code
11530
Country
United States
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
City
Riverton
State/Province
Utah
ZIP/Postal Code
84065
Country
United States
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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