Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus; Secondary Hypogonadism
MeSH terms: Neoplasm Metastasis; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypogonadism
Intervention: Placebo; Androxal
Intervention description: Placebo capsule 1x daily for 3 months; Capsules 12.5 mg or 25 mg 1x daily for 3 months
Intervention MeSH terms: Enclomiphene; Clomiphene; Zuclomiphene
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 102.0
Sex: Male
Minimum age: 20 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Adult onset hypogonadotropic hypogonadism

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
    

Eligibility criteria:

        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.