Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Randomized, double blind, placebo-controlled clinical trial examining the efficacy and safety of mifepristone 600 mg daily in male subjects with type 2 diabetes mellitus, not associated with Cushing's syndrome

Detailed Description
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Randomized, double blind, placebo-controlled clinical trial examining the efficacy and safety of mifepristone 600 mg daily in male subjects with type 2 diabetes mellitus, not associated with Cushing's syndrome, and sub-optimally controlled on basal insulin, with or without prandial insulin and/or maximally-tolerated doses of metformin.

Official Title
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Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus, Insulin Resistance

Intervention / Treatment
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* Drug: Mifepristone 600 mg daily
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Males Age 18-65 inclusive Established T2DM for ≥ 1 year Taking stable doses (≤ 20% change in total daily insulin dose within 2 months prior to screening) of basal insulin, with or without prandial insulin (total daily dose must be ≤ 200 units) Baseline hemoglobin A1c (HbA1c) 8.0%-10.5% Exclusion criteria: No use of any anti-hyperglycemic agents (oral or injectable) other than metformin or insulin No history or clinical suspicion of type 1 diabetes mellitus No concurrent chronic use of any corticosteroids by any route and for any indication, or concurrent conditions that may require the initiation of glucocorticoids during the study No concurrent lipid-lowering medications whose levels are dependent on CYP3A pathway clearance (e.g., simvastatin, lovastatin, atorvastatin, fluvastatin and rosuvastatin) should either be washed out for at least one month prior to enrollment and/or switched to alternative LDL-cholesterol lowering agents (e.g., pravastatin or ezetimibe) for at least one month. No contraindications or known intolerance to mifepristone No concurrent use of strong CYP3A inhibitors (e.g., cyclosporine, ergotamine, fentanyl, quinidine, sirolimus, tacrolimus, imidazole antifungals, HIV protease inhibitors, certain macrolide antibiotics) No concurrent use of CYP3A inducers (e.g., phenytoin, phenobarbital, carbamazepine, rifampin) No concurrent use of medications that may prolong the QT interval (e.g., selected antipsychotics and antidepressants, quinolone antibiotics) No daily use of warfarin or non-steroidal anti-inflammatory agents Baseline K+ and Mg+2 within the laboratory normal ranges, with or without oral K+ and/or Mg+2 supplementation Fasting plasma glucose (FPG) averaging < 280 mg/dL and without polyuria or polydipsia No symptomatic hypoglycemia averaging > once per day Able and willing to perform self-monitoring of blood glucose (SMBG) Mean BP < 140 mmHg systolic or 90 mm Hg diastolic Baseline LDL-cholesterol < 200 mg/dL if on lipid-lowering therapy or < 250 mg/dL while not on lipid-lowering therapy Fasting triglycerides ≤ 500 mg/dL if on lipid-lowering therapy HDL-cholesterol ≥ 25 mg/dL No known history of prostate cancer, or elevated level of prostate-specific antigen (PSA) at screening Estimated GFR ≥ 30 mL/min No concurrent endocrinopathies that have not been stabilized with replacement or other definitive therapies (including known adrenal insufficiency regardless of replacement therapy, cortisol < 5 μg/dL at screening) No active hemolytic anemias or hemoglobin variants that render the measurement of HbA1c potentially unreliable No other clinically significant hepatic, cardiovascular (including known personal or family history of, or risk factors for long-QT syndrome, QTcF prolongation on ECG > 500 ms), infectious (including HIV or any viral hepatitis), inflammatory, neoplastic or other systemic disease that may contraindicate the change of lipid-lowering therapy, renders mifepristone unsafe, or otherwise confounds data interpretation Subjects not likely to start other drugs that may influence the study's outcomes (e.g., weight loss agents) Subjects who are able and willing to comply with all components of the study protocol, attend all scheduled follow-up visits, or who do not present other foreseeable barriers that might make the implementation of the protocol problematic or confound data interpretation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mifepristone 600 mg daily<br>Mifepristone 300 mg po daily x 2 weeks, followed by mifepristone 600 mg po daily x 10 weeks | Drug: Mifepristone 600 mg daily<br>* Glucocorticoid receptor antagonist<br>* Other names: Korlym;|
| Placebo Comparator: Placebo<br>Matching, blinded placebo 1 tablet po daily x 2 weeks, followed by matching, blinded placebo 2 tablets po daily x 10 weeks | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c | Glycemic lowering | Baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Weight in kg | Baseline to 3 months | 
| Body Mass Index | Body mass index in kg/m^2 | Baseline to 3 months | 
| Systolic BP | Systolic blood pressure | Baseline to 3 months | 
| Diastolic BP | Diastolic blood pressure | Baseline to 3 months | 
| LDL-cholesterol | Low-density lipoprotein cholesterol | Baseline to 3 months | 
| Cortisol | Serum cortisol level (AM) | Baseline to 3 months | 
| ACTH | Serum adrenocorticotrophic hormone level (AM) | Baseline to 3 months | 
| Uric Acid | Serum uric acid level | Baseline to 3 months | 
| PSA | Prostate-specific antigen level | Baseline to 3 months | 
| Hypoglycemic Events | Symptomatic mild and severe hypoglycemic events | Baseline to 3 months | 
| Adverse Events | Non-hypoglycemia-related adverse events | Baseline to 3 months | 
| Basal Insulin Dose | Total daily basal insulin dosage | Baseline to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes mellitus, insulin resistance, mifepristone, glucocorticoids