Study of CRx-401 on Glucose Levels in Subjects With Type II Diabetes

Condition(s) targeted: Type 2 Diabetes

Intervention: bezafibrate + diflunisal (Drug); bezafibrate + placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: CombinatoRx

Official(s) and/or principal investigator(s):
Tim Zmijowskyj, MD, Principal Investigator, Affiliation: Medicor Research Inc.

Overall contact:
Geraldine Lyons, Phone: 617-301-3000

This trial will assess the efficacy of CRx-401 in lowering FPG levels in patients taking metformin to treat their diabetes. In addition, this initial trial will evaluate insulin resistance (HOMA-IR index), HgbA1c levels, glycated protein, LDL, HDL, triglycerides, and total cholesterol, as well as the safety of CRx-401.

Official title: A Randomized, Multi-Center Study to Compare the Effects of CRx-401 to Bezafibrate Plus Placebo on Plasma Glucose Levels When Given to Subjects With Type II Diabetes on Metformin.

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: The primary efficacy endpoint will measure change in fasting plasma glucose from Baseline to Day 90

Secondary outcome: The exploratory efficacy endpoints will measure change in the following parameters: HOMA Index, HgbA1C, fructosamine, LDL, HDL, OGTT, triglycerides and total cholesterol from Baseline to Day 90

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Must voluntarily give written informed consent

- Must be between 18-75 years of age

- Must have Type 2 diabetes for ≥ 6 months

- HgbA1C between 7. 0% and 9. 5%

- FPG > 6. 7 mmol/L (120 mg/dL)

- BMI: Lower limit of 27 kg/m2 and an upper Limit of 45 kg/m2

- Treatment with a stable dosage for ≥ 8 weeks of either Glucophage metformin) ≥ 1000

and ≤ 2500 mg/day OR Glucophage XR ≤ 2000 mg/day

- eGFR ≥ 70 mL/min

Exclusion Criteria:

- History of any clinically significant atherosclerotic disorder including myocardial

infarction (within 6 months of screening), angina, stroke, peripheral vascular disease or congestive heart failure

- Known hypersensitivity or idiosyncratic reaction related to fibrates or NSAIDs

including photo-allergic or phototoxic reactions to fibrates

- Subjects in whom acute asthmatic attacks, urticaria, or rhinitis are precipitated by

aspirin or other NSAIDs

- History of clinically significant (as determined by the investigator cardiac,

hematologic, hepatobiliary, peptic ulcer, renal, immunologic, metabolic, urologic, pulmonary, endocrinologic, neurologic, dermatologic, psychiatric, and/or other major disease

- Type 1 Diabetes

- Evidence of Cushing's syndrome, untreated hypothyroidism or other disorders that may

lead to secondary weight gain, insulin resistance, or Type 2 diabetes

- Proliferative diabetic retinopathy or significant neuropathic symptoms that also limit

activities of daily living

- History of malignancy (except for treated or excised basal cell carcinoma)

- Surgery within the 90 days prior to screening except for minor dental or cosmetic

procedures

- History of drug or alcohol abuse (as defined by the Investigator)

- History of opportunistic infection

- Serious local infection (e. g., cellulitis, abscess) or systemic infection (e. g.,

septicemia) within 3 months prior to screening

- Fever or symptomatic viral or bacterial infection within 2 weeks prior to screening

- Positive for HCV antibody

- Positive for HBsAg

- Known positive for HIV antibody

- Pharmacologic treatment with statins, unless dosage has been stable ≥ three months and

is unlikely to change over the course of the study.

- Treatment with any concomitant medication that has not been at a stable dose for at

least 28 days prior to screening.

- Currently taking or planning to take during the trial:

Sulphonylureas, Injected hypoglycemic (exanatide or insulin), Weight loss medications, Thiazolidenediones, Glucocorticoids (inhaled glucocorticoids are permitted), Digoxin, Anticoagulants, Phenytoin, Loratadine, Erythromycin, MAO-inhibitors, NSAIDs (ASA ≤ 81 mg/d is permitted), COX-2 Inhibitors, Cholestryramine or fibrates, DPP-IV inhibitors, Any herbal medications unless reviewed with study doctor

- Alanine aminotransferase ALT) or aspartate aminotransferase (AST laboratory values

that exceed > 2. 0 x upper limit of normal (ULN)

- White blood cell (WBC) count < 4. 0 x 109 /L or >14. 0 X 109 /L

- Hemoglobin < 105 g/L in females and < 110 g/L in males (< 10. 5 g/dL in females and <

11. 0 g/dL in males)

- Participation in another clinical trial and/or treatment received with any

investigational agent within 30 days before the initial dose of study medication

- Female subject who is pregnant or lactating or of child bearing potential and not

using acceptable methods of contraception (birth control pills, barriers or abstinence)

- Unwilling or unable to comply with the requirements of this protocol, including the

presence of any condition (physical, mental, or social) that is likely to affect the subject's return for follow-up visits on schedule

- Other unspecified reasons that, in the opinion of the Investigator or sponsor make the

subject unsuitable for enrollment

Geraldine Lyons, Phone: 617-301-3000

Chilliwack, British Columbia, Canada; Recruiting

Vancouver, British Columbia, Canada; Recruiting

Winnipeg, Manitoba, Canada; Recruiting

St. Johns, Newfoundland and Labrador, Canada; Recruiting

Bay Roberts, Newfoundland and Labrador, Canada; Recruiting

Holyroad, Newfoundland and Labrador, Canada; Recruiting

Sudbury, Ontario, Canada; Recruiting

Newmarket, Ontario, Canada; Recruiting

Toronto, Ontario, Canada; Recruiting

Aylmer, Ontario, Canada; Recruiting

Sarnia, Ontario, Canada; Recruiting

Corunna, Ontario, Canada; Recruiting

London, Ontario, Canada; Recruiting

Collingwood, Ontario, Canada; Recruiting

Robarts Research Institute, London, Ontario, Canada; Recruiting

Burlington, Ontario, Canada; Recruiting

Montreal, Quebec, Canada; Recruiting

Saskatoon, Saskatchewan, Canada; Recruiting

Starting date: July 2007
Ending date: March 2009
Last updated: October 20, 2008