Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus

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.

- 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