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Study to Evaluate the Safety, Tolerability and Efficacy of Three Dose Levels of Mitoglitazone in Type 2 Diabetic Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Metabolic Solutions Development Company
ClinicalTrials.gov Identifier:
NCT01103414
First received: April 7, 2010
Last updated: April 23, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to evaluate the safety, tolerability and efficacy of three dose levels of Mitoglitazone™ (MSDC-0160) in patients with type 2 diabetes.


Condition Intervention Phase
Type 2 Diabetes
Drug: Mitoglitazone
Drug: Pioglitazone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2B, Randomized, Double-Blind, Comparator- & Placebo-Controlled, Dose Ranging Study to Evaluate Safety, Tolerability & Efficacy of 3 Dose Levels of Mitoglitazone in Type 2 Diabetic Patients

Resource links provided by NLM:


Further study details as provided by Metabolic Solutions Development Company:

Primary Outcome Measures:
  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12. [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    Change from baseline in fasting plasma glucose in response to three different doses of Mitoglitazone as compared to pioglitazone following once-daily dosing for 84 consecutive days (12 weeks) in patients with Type 2 diabetes.


Secondary Outcome Measures:
  • Change From Baseline in HbA1c [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change from baseline in plasma glucose measured by hemoglobin A1c in response to three different doses of Mitoglitazone and pioglitazone as compared to placebo following once-daily dosing for 84 consecutive days (12 weeks) in patients with Type 2 diabetes.

  • Percent Change From Baseline to Week 12 Endpoint in HMW Adiponectin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percent change from baseline to week 12 endpoint in high molecular weight adiponectin

  • Change From Baseline to Week 12 Endpoint in Hematocrit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change from baseline to week 12 endpoint in hematocrit as an indication of fluid retention

  • Change From Baseline in Hemoglobin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change from baseline at week 12 endpoint in hemoglobin concentration

  • Change From Baseline in RBC [ Time Frame: 12 week ] [ Designated as safety issue: No ]
    Change from baseline at week 12 endpoint in red blood cell concentration

  • Change in Body Weight From Baseline to Week 12 Endpoint [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Effects of 3 different doses of Mitoglitazone and pioglitazone as compared to placebo on body weight following once-daily dosing for 12

  • Change From Baseline in Waist Circumference at Week 12 Endpoint [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Effects of 3 different doses of Mitoglitazone and pioglitazone as compared to placebo on waist circumference following once-daily dosing for 12 weeks

  • Presence of Edema Post Baseline During 12 Weeks Active Treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Effects of 3 different doses of Mitoglitazone and pioglitazone as compared to placebo on presence of edema following once-daily dosing for 12 weeks

  • Changes in HDL Particle Size Subfractions From Baseline to Week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Effects of 3 different doses of Mitoglitazone and pioglitazone as compared to placebo on HDL particle size profile as characterized by changes in NMR analysis of subfractions following once-daily dosing for 12 weeks

  • Changes in LDL Particle Size Subfractions From Baseline to Week 12 [ Time Frame: 12 week ] [ Designated as safety issue: No ]
    Effects of 3 different doses of Mitoglitazone and pioglitazone as compared to placebo on LDL particle size profile as characterized by changes in NMR analysis of subfractions following once-daily dosing for 12 weeks


Enrollment: 356
Study Start Date: September 2010
Study Completion Date: December 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mitoglitazone 50 mg capsules
Mitoglitazone 50 mg capsules self administered once-daily each morning after an overnight fast and 30 minutes before the morning meal for 84 days.
Drug: Mitoglitazone
50 mg capsules, once daily for 84 days
Other Name: MSDC-0160
Experimental: Mitoglitazone 100 mg capsules
Mitoglitazone 100 mg capsules self administered once-daily each morning after an overnight fast and 30 minutes before the morning meal for 84 days.
Drug: Mitoglitazone
Mitoglitazone 100 mg capsules, once daily for 84 days
Other Name: MSDC-0160
Experimental: Mitoglitazone 150 mg capsules
Mitoglitazone 150 mg capsules self administered once-daily each morning after an overnight fast and 30 minutes before the morning meal for 84 days.
Drug: Mitoglitazone
Mitoglitazone 150 mg capsules, once daily for 84 days
Other Name: MSDC-0160
Active Comparator: Pioglitazone 45 mg capsules
Pioglitazone 45 mg capsules self administered once-daily each morning after an overnight fast and 30 minutes before the morning meal for 84 days.
Drug: Pioglitazone
Pioglitazone 45 mg, once daily for 84 days
Other Name: ACTOS
Placebo Comparator: Matching placebo
Placebo capsules self administered once-daily each morning after an overnight fast and 30 minutes before the morning meal for 84 days.
Drug: Placebo
Placebo, once daily for 84 days

Detailed Description:

The primary study objectives are to characterize the reduction in fasting plasma glucose in response to three different doses of Mitoglitazone as compared to placebo following once-daily dosing for 84 consecutive days (12 weeks) in patients with Type 2 diabetes and to investigate the safety and tolerability of three different doses of Mitoglitazone following once-daily dosing for 84 consecutive days (12 weeks) in patients with Type 2 diabetes.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Males and females with Type 2 diabetes (fasting plasma glucose ≥126 mg/dL at screening, glycosylated hemoglobin [HbA1c] >7 and ≤10%, and Insulin C-peptide >1 ng/mL). Patients can be naïve to diabetes therapy or if taking metformin should be on a stable dose level for a period of at least 3 months prior to screening visit (no dose limit).
  2. Between the ages of 18-75 years, inclusive.
  3. Females should be either postmenopausal (at least 12 months since last menses) or surgically sterilized (bilateral tubal ligation or hysterectomy). Menopausal status will be verified by a follicle-stimulating hormone (FSH) test. If FSH levels are below 40 mIL/mL, some method of birth control must be used. Those with bilateral tubal ligation must also use a barrier method of birth control. In addition, all females must have a negative pregnancy test at Screen and Day 15 regardless of childbearing potential. Males with female partners of child-bearing potential must agree to use adequate contraceptive methods (including a condom, plus one other form of contraception) if engaging in sexual intercourse.
  4. Body Mass Index (BMI) = 23 kg/m2 to 45 kg/m2 (inclusive).
  5. Willing and able to make a screening visit to the clinic and seven visits over a 21 week period.
  6. Willing and able to sign an informed consent document indicating understanding the purpose of and procedures required for the study and willingness to participate in the study.

Exclusion Criteria

  1. Use of TZDs or diabetes medications other than metformin (generic or Glucophage®) 3 months prior to screening.
  2. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.
  3. Fasting plasma glucose in excess of 240 mg/dl at screening
  4. History of heart failure (including CHF) or previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 6 months prior to screening.
  5. ALT and/or AST levels that are twice the upper limit of normal; bilirubin levels that exceed 2 mg/dL; serum creatinine >1.5 mg/dL in men or > 1.4 mg/dL in women.
  6. History nephropathy, neuropathy, or retinopathy within 6 months of screening.
  7. Use of glucocorticoids (oral, injectible, intraarticular, or chronic inhaled) or weight-loss drugs within 3 months of randomization.
  8. Current or recurrent disease that may affect the action, absorption or disposition of the study treatment, or clinical or laboratory assessments.
  9. Current or history of severe or unstable disorder (medical or psychiatric) requiring treatment that may make the patient unlikely to complete the study.
  10. Febrile illness within the 5 days prior to the first dose.
  11. Known history of HIV, hepatitis B, or hepatitis C.
  12. Clinically significant findings on physical examination, including BP, pulse rate and 12-lead ECG.
  13. Blood pressure greater than 160/100 mmHg. Patients with elevated BP (<160/100 mmHg) with or without current treatment will be allowed at the discretion of the Principal Investigator (PI) and primary care physician. Individuals with hypertension must have been stabilized to the current treatment regimen for at least 6 weeks prior to screening.
  14. Change in BP or lipid-lowering medication within 6 weeks or change in dose of metformin or thyroid replacement within 3 months prior to screening.
  15. Known or suspected intolerance or hypersensitivity to the study drugs, closely related compounds or any of their stated ingredients.
  16. History of alcohol or drug abuse within 6 months of Screening.
  17. Have participated in an investigational study or received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration.
  18. Blood donation of 1 pint or more within 56 days of screening.
  19. Plasmapheresis or plasma donation within 30 days of screening.
  20. Single 12-lead ECG demonstrating a QTc >450 msec at Screening. A single repeat ECG may be done at the investigator's discretion.
  21. Any surgical or medical condition which may significantly alter the absorption of any drug substance including, but not limited to, any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active inflammatory bowel syndrome.
  22. Evidence of clinically relevant pathology that could interfere with the study results or put the patient's safety at risk.
  23. Malignancy, including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01103414

Locations
United States, Alabama
Huntsville, Alabama, United States
Muscle Shoals, Alabama, United States
United States, California
Chino, California, United States
Los Angeles, California, United States
Spring Valley, California, United States
Walnut Creek, California, United States
United States, Florida
Miami, Florida, United States
New Port Richley, Florida, United States
Palm Harbor, Florida, United States
Pembroke Pines, Florida, United States
United States, Georgia
Marietta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Michigan
Grand Rapids, Michigan, United States
United States, Ohio
Cincinnati, Ohio, United States
Kettering, Ohio, United States
Tiffin, Ohio, United States
United States, Oklahoma
Oklahoma City, Oklahoma, United States
United States, Oregon
Eugene, Oregon, United States
Portland, Oregon, United States
United States, South Carolina
Greer, South Carolina, United States
United States, Texas
Corpus Christi, Texas, United States
Houston, Texas, United States
San Antonio, Texas, United States
Sponsors and Collaborators
Metabolic Solutions Development Company
Investigators
Study Director: Jerry R Colca, PhD MSDC
  More Information

No publications provided

Responsible Party: Metabolic Solutions Development Company
ClinicalTrials.gov Identifier: NCT01103414     History of Changes
Other Study ID Numbers: MSDC-C004
Study First Received: April 7, 2010
Results First Received: February 15, 2013
Last Updated: April 23, 2013
Health Authority: United States: Food and Drug Administration
India: Drugs Controller General of India
India: Institutional Review Board

Keywords provided by Metabolic Solutions Development Company:
Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014