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

NCT01706211 | Completed Phase 3 DMC

• 1 other identifier: 49653/128
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus Non Insulin Dependent Oral Agent Therapy

Keywords

non insulin dependent diabetes mellitus, rosiglitazone

Outcome Measures

Primary Outcomes (1)

• To determine the effectiveness of BRL 49653C (2 mg bd) compared to placebo when added to sulphonylurea therapy, for 24 weeks in out-patients with NIDDM.

  Primary: Change from baseline for Hb A1c at week 24. Secondary: Mean change from baseline for: fasting plasma glucose,insulin levels, immune reactive,lipid levels (ie.total cholesterol, HDL-cholesterol, LDL cholesterol, triglycerides), body weight (WHR), vital signs (systolic, diastolic blood pressure and heart rate)

  7 months

Secondary Outcomes (1)

• To assess the clinical safety of BRL 49653C (2 mg bd) compared to placebo when added to sulphonylurea therapy, for 24 weeks in out-patients with NIDOM.

  7 months

Study Arms (2)

BRL 49653C

EXPERIMENTAL

Eligible patients may enter the study at visit 1 according to the inclusion/exclusion criteria. At the screening visit, patients will enter a single blind placebo run-in period to establish baseline characteristics. Patients must have been stable on sulphonylurea therapy for at least 2 months prior to the screening visit to be included. For the duration of the run-in period, patients will receive BRL 49653C placebo in addition to their constant dose of sulphonylurea. Patients eligible to enter the double-blind phase of the study will be randomized in equal numbers at visit 2, to one of two treatment groups (BRL 49653C 2 mg bid. or placebo bid). Patients will then continue to take their study medication arid the constant dose of sulphonylurea through visits 3 to 8 (weeks 4 to 24).

Drug: BRL 49653C

placebo

PLACEBO COMPARATOR

Eligible patients may enter the study at visit 1 according to the inclusion/exclusion criteria. At the screening visit, patients will enter a single blind placebo run-in period to establish baseline characteristics. Patients must have been stable on sulphonylurea therapy for at least 2 months prior to the screening visit to be included. For the duration of the run-in period, patients will receive BRL 49653C placebo in addition to their constant dose of sulphonylurea. Patients eligible to enter the double-blind phase of the study will be randomized in equal numbers at visit 2, to one of two treatment groups (BRL 49653C 2 mg bid. or placebo bid). Patients will then continue to take their study medication arid the constant dose of sulphonylurea through visits 3 to 8 (weeks 4 to 24).

Drug: Placebo

Interventions

BRL 49653C DRUG

BRL 49653C 2 mg bid or placebo bid through weeks 1 to 24.

Also known as: Avandia, rosiglitazone

BRL 49653C

Placebo DRUG

placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan, 10002, Taiwan

Location

Related Publications (1)

• Yang WS, Jeng CY, Wu TJ, Tanaka S, Funahashi T, Matsuzawa Y, Wang JP, Chen CL, Tai TY, Chuang LM. Synthetic peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care. 2002 Feb;25(2):376-80. doi: 10.2337/diacare.25.2.376.

  PMID: 11815513 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Lee-Ming Chuang, PHD

  National Taiwan University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2012
• First Posted: October 15, 2012
• Study Start: October 1, 1998
• Primary Completion: April 1, 2000
• Study Completion: April 1, 2000
• Last Updated: October 15, 2012

Record last verified: 2012-09

Locations

TW (1)