Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus

Sponsor

Charles Drew University of Medicine and Science (Other)

Overall Status

Terminated

CT.gov ID

NCT03052400

Collaborator

(none)

Enrollment

Location

Arms

51.8

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Insulin Resistance	Drug: Mifepristone 600 mg daily Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus

Actual Study Start Date :

Feb 3, 2017

Actual Primary Completion Date :

Mar 31, 2021

Actual Study Completion Date :

May 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mifepristone 600 mg daily Mifepristone 300 mg po daily x 2 weeks, followed by mifepristone 600 mg po daily x 10 weeks	Drug: Mifepristone 600 mg daily Glucocorticoid receptor antagonist Other Names: Korlym
Placebo Comparator: Placebo Matching, blinded placebo 1 tablet po daily x 2 weeks, followed by matching, blinded placebo 2 tablets po daily x 10 weeks	Drug: Placebo Matching placebo

Arm

Intervention/Treatment

Experimental: Mifepristone 600 mg daily

Mifepristone 300 mg po daily x 2 weeks, followed by mifepristone 600 mg po daily x 10 weeks

Drug: Mifepristone 600 mg daily

Glucocorticoid receptor antagonist

Other Names:

Korlym

Placebo Comparator: Placebo

Matching, blinded placebo 1 tablet po daily x 2 weeks, followed by matching, blinded placebo 2 tablets po daily x 10 weeks

Drug: Placebo

Matching placebo

Outcome Measures

Primary Outcome Measures

Hemoglobin A1c [3 months]
Glycemic lowering

Secondary Outcome Measures

Weight [3 months]
Weight in kg
Body mass index [3 months]
BMI in kg/m2
Fat mass [3 months]
Percentage total body fat mass
Lean body mass [3 months]
Percentage total body lean mass
Insulin resistance [3 months]
HOMA and OGTT dynamic measures
Fasting lipids [3 months]
Fasting lipids and lipoproteins
Blood pressure [3 months]
Systolic and diastolic BP
Hypoglycemic events [3 months]
Symptomatic mild and severe hypoglycemic events
Adverse events [3 months]
Non-hypoglycemia-related adverse events
Insulin dose [3 months]
Total daily insulin dosage

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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%
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