Secondary Hypogonadism, Type 2 Diabetes Mellitus
Conditions
Keywords
Adult onset hypogonadotropic hypogonadism
Brief summary
The purpose of this study is to determine the effect the investigative drug has on glycemic control in men with type 2 diabetes mellitus (T2DM) and secondary hypogonadism
Detailed description
A phase IIB, multi-center, randomized, parallel, placebo- and active-controlled trial in adult male subjects with secondary hypogonadism who have been treated with OHAs but are not in glycemic control. All subjects currently treated with exogenous testosterone will discontinue at screening for at least 21 days and remain off testosterone for the course of the study. One hundred twenty to 150 subjects will be randomly assigned to one of three treatment groups according to a 1:1:1 ratio. Subjects will receive one of two dose strengths of Androxal or placebo in addition to their usual dose of mono- or combination OHAs for three months. Following an initial screening period, subjects will return monthly for 3 months and 1 month later for a follow-up visit.
Interventions
DRUGPlacebo
Placebo capsule 1x daily for 3 months
DRUGAndroxal
Capsules 12.5 mg or 25 mg 1x daily for 3 months
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Males, ages 20 to 80-years-old, inclusive * A diagnosis of type 2 diabetes mellitus by American Diabetes Association (ADA) criteria for at least 6 months * Treatment with a stable but sub-optimum dose of OHAs for at least 2 months prior to screening based on a lack of control of blood glucose * Previous diagnosis of adult-onset idiopathic hypogonadotropic hypogonadism (AIHH) and have undergone treatment with a topical testosterone gel, Low-to-borderline morning total testosterone (TT), after at least a two week wash-out period, and normal or low normal serum luteinizing hormone (LH)at screening and at baseline * No previous diagnosis of AIHH but present as naïve patients with low morning TT and normal or low normal serum LH at screening and at baseline * Body Mass Index (BMI) between 26 and 40 kg/m2 * Fasting blood (plasma or serum) glucose (FBG) between 125 and 240 mg/dL * HemoglobinA1c in serum as (HbA1c) between 7% and 9.5% * Comprehends informed consent * Otherwise normal healthy males * All clinical laboratory test within normal ranges (any deviation outside the normal range will require approval of investigator) * Ability to complete the study in compliance with the protocol * Ability to understand and provide written informed consent
Exclusion criteria
* A history of testicular failure, Kallmann Syndrome or other infertility condition * Clinically significant medical condition rendering the subjects infertile including tumors of the pituitary, laboratory abnormalities, or having received an investigational drug in the past 30 days prior to study * Prostate nodules or induration, a history of, known, or suspect prostate cancer not ruled out by a negative biopsy, or a prostate specific antigen (PSA) higher than 3.5; * Hematocrit in excess of 47% or a hemoglobin (Hb) greater than 16 g/dl * Previous treatment with androgens, estrogens, DHEA, testosterone or testosterone analogues in injectable, oral, topical or other forms for the treatment of AIHH who have not discontinued at the start of the treatment phase; * Primary hypogonadism as typified as a serum LH greater than 15 and a TT value less than 300 ng/dL * Continuous use of corticosteroids * History of or current diagnosis of major macrovascular complications of T2DM: myocardial infarction (MI) or stroke within 6 months, or any history of coronary revascularization, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) greater than or equal to 2 * Uncontrolled sitting blood pressure (BP) greater than 150/95, serum creatinine (Cr) greater than 1.5 ULN or estimated glomerular filtration rate (eGFR) less than mL/min/1.73 m2 * Retinopathy requiring continuing ophthalmologic assessments * Cataracts * Other significant history of diabetic complications (proteinuria greater than 1 g/d, retinopathy, clear neuropathy) * Aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase greater than 3 times the upper limits of normal (ULN) * Total bilirubin greater than 2.0 mg/dL (\>34 µmol/L); * Injectable testosterone within 120 days of Screening (Visit 1) * Reported substance abuse at screening * Taking insulin therapy; * Clinically significant abnormal findings on screening examination as determined by the investigator * Known hypersensitivity to clomiphene citrate; * Current or history of breast cancer * Any condition which in the opinion of the investigator would interfere with the participant's ability to provide informed consent, comply with the study instructions, possibly confound interpretation of the study results, or endanger the participant if he took part in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1C | 3 months | The change in HbA1c from Baseline to 3 Months for each treatment arm |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo
Placebo: Placebo capsule 1x daily for 3 months | 43 |
| Androxal 12.5 mg 12.5 mg/day
Androxal: Capsules 12.5 mg or 25 mg 1x daily for 3 months | 38 |
| Androxal 25 mg 25 mg/day
Androxal: Capsules 12.5 mg or 25 mg 1x daily for 3 months | 38 |
| Total | 119 |
Baseline characteristics
| Characteristic | Placebo | Androxal 12.5 mg | Androxal 25 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 8.4 | 55.9 years STANDARD_DEVIATION 9.5 | 57.6 years STANDARD_DEVIATION 8.4 | 57.0 years STANDARD_DEVIATION 8.7 |
| HgbA1c ratio | 0.08 Ratio STANDARD_DEVIATION 0.012 | 0.08 Ratio STANDARD_DEVIATION 0.013 | 0.09 Ratio STANDARD_DEVIATION 0.017 | 0.08 Ratio STANDARD_DEVIATION 0.014 |
| Region of Enrollment United States | 43 participants | 38 participants | 38 participants | 119 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 43 Participants | 38 Participants | 38 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 43 | 8 / 38 | 5 / 38 |
| serious Total, serious adverse events | 1 / 43 | 0 / 38 | 1 / 38 |
Outcome results
Primary
Change in HbA1C
The change in HbA1c from Baseline to 3 Months for each treatment arm
Time frame: 3 months
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in HbA1C | 0 Ratio | Standard Deviation 0.012 |
| Androxal 12.5 mg | Change in HbA1C | 0 Ratio | Standard Deviation 0.015 |
| Androxal 25 mg | Change in HbA1C | 0 Ratio | Standard Deviation 0.01 |