Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus

• ClinicalTrials.gov Identifier: NCT03052400
• Recruitment Status: Terminated
• First Posted: February 14, 2017
• Results First Posted: October 19, 2022
• Last Update Posted: May 18, 2023
• Sponsor: Charles Drew University of Medicine and Science
• Information provided by (Responsible Party): Stanley Hsia, Charles Drew University of Medicine and Science

Study Description

Brief Summary:

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

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 (Clinical Trial)
• 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: February 3, 2017
• Actual Primary Completion Date: March 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 Name: 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 :

1. Hemoglobin A1c [ Time Frame: Baseline to 3 months ]
   Glycemic lowering

Secondary Outcome Measures :

1. Weight [ Time Frame: Baseline to 3 months ]
   Weight in kg
2. Body Mass Index [ Time Frame: Baseline to 3 months ]
   Body mass index in kg/m^2
3. Systolic BP [ Time Frame: Baseline to 3 months ]
   Systolic blood pressure
4. Diastolic BP [ Time Frame: Baseline to 3 months ]
   Diastolic blood pressure
5. LDL-cholesterol [ Time Frame: Baseline to 3 months ]
   Low-density lipoprotein cholesterol
6. Cortisol [ Time Frame: Baseline to 3 months ]
   Serum cortisol level (AM)
7. ACTH [ Time Frame: Baseline to 3 months ]
   Serum adrenocorticotrophic hormone level (AM)
8. Uric Acid [ Time Frame: Baseline to 3 months ]
   Serum uric acid level
9. PSA [ Time Frame: Baseline to 3 months ]
   Prostate-specific antigen level
10. Hypoglycemic Events [ Time Frame: Baseline to 3 months ]
    Symptomatic mild and severe hypoglycemic events
11. Adverse Events [ Time Frame: Baseline to 3 months ]
    Non-hypoglycemia-related adverse events
12. Basal Insulin Dose [ Time Frame: Baseline to 3 months ]
    Total daily basal insulin dosage

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Charles Drew University of Medicine and Science

Los Angeles, California, United States, 90059

Sponsors and Collaborators

Charles Drew University of Medicine and Science

Investigators

• Principal Investigator: Stanley H Hsia, MD; Charles Drew University of Medicine and Science

  Study Documents (Full-Text)

Documents provided by Stanley Hsia, Charles Drew University of Medicine and Science:

Study Protocol and Statistical Analysis Plan  [PDF] September 15, 2020

More Information

• Responsible Party: Stanley Hsia, Associate Professor of Medicine, Charles Drew University of Medicine and Science
• ClinicalTrials.gov Identifier: NCT03052400
• Other Study ID Numbers: 16-04-2482
• First Posted: February 14, 2017
• Results First Posted: October 19, 2022
• Last Update Posted: May 18, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data sharing as per NIH funding requirements
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: After publication
• Access Criteria: Contact investigator

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stanley Hsia, Charles Drew University of Medicine and Science:

type 2 diabetes mellitus; insulin resistance; mifepristone; glucocorticoids

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Mifepristone; Abortifacient Agents, Steroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptive Agents; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Luteolytic Agents; Contraceptive Agents, Hormonal; Menstruation-Inducing Agents