A Study to Evaluate the Efficacy and Safety of BRL 49653C in Non-insulin Dependent Diabetes

• Status: Completed
• Trial end date: 2000-04-01
• Target enrollment: 0
• Participant gender: All

Summary

At least 30% of patients initially treated with sulphonylureas for NIDOM will have a poor response, and in the remaining 70% the subsequent failure rate is approximately 4% to 5% per year. BRL 49653C has a different mechanism of action to the sulphonylureas, and therefore the effects on fasting plasma glucose and Hb A1c are expected to be additive. Since circulatory insulin levels should decrease, and plasma glucose should be regulated, these combinations are also anticipated to slow both the progression of diabetic complications and delay the need for exogenous insulin.

The proposed study is intended primarily to determine the effectiveness of BRL 49653C by measure of glucose homeostasis as determined by Hb A1c and fasting plasma glucose, when added to sulphonylurea therapy (sulphonylureas are limited to: glibenclamide, glipazide and gliclazide). In addition, the clinical safety of BRL 49653C will be assessed in this patient population. The starting doses have been selected based on dose response studies examining safety, tolerability and efficacy in the U.S.A.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Taiwan University Hospital
• Treatments: Rosiglitazone

Criteria

Inclusion Criteria:

• Men or women between 30-80 years of age inclusive at time of enrolment.

• Patients who had non-independent diabetes mellitus (NIDDM) defined by the criteria of the National Diabetes Data Group.

• Patients who had sulphonylurea therapy for at least 6 months and a constant dose for at least 2 months prior to visit 1.

• Patients who had fasting plasma glucose <= 15.0 mmol/L at screening. Hemoglobin A1c >= 7.5%.

• Female patients must be (1) post-menopausal, i.e. > 6 months without menstrual period, surgically sterile, or (2) using hormonal contraceptives or intrauterine contraceptive devices. Female patients who were taking hormonal contraceptives must also use an additional barrier form or intrauterine form of birth control.

• Patients who had given their written informed consent to participate.

Exclusion Criteria:

• Female patients who were pregnant, breast feeding or planning a pregnancy during the course of the study.

• Patients who had a fasting plasma glucose > 15.0 mmol/L at screening, or severity of diabetes mellitus requiring administration of insulin, or patients with ketonuria.

• Patients who had clinically significant renal or hepatic disease (i.e., patients with serum creatinine > 160 micromol/L (1.8 mg/dL); ALT, AST, total bilirubin, gamma GT, or alkaline phosphatase more than 2.5 times the upper limit of the normal laboratory range).

• Any clinically significant abnormality identified on the screening physical examination, laboratory tests, electrocardiogram which in the judgment of the investigator would preclude safe completion of the study.

• Patients who had leukocyte count < 3000/mm3 or platelet count <120,000/mm3.

• Systolic blood pressure >180mmHg or diastolic blood pressure >114mmHg while on appropriate hypertensive therapy.

• Significant anemia (hemoglobin < 11 g/dL for males or < 10g/dL for females) or diagnosis of porphyria.

• Symptomatic diabetic neuropathy of sufficient severity to require treatment for control of symptoms (eg, painful peripheral neuropathy, symptomatic orthostatic hypotension, urinary retention, gastric stasis, pedal ulcers).

Diabetic retinopathy imminently requiring treatment for preserving or restoring vision.

• Body mass index(BMI) < 22 and >38 kg/m2 (Formula: BMI= weight, kg ÷height, m2)and variation in body weight of >=5% between screening and visit2.