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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01706211
First received: October 10, 2012
Last updated: October 12, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus Non Insulin Dependent Oral Agent Therapy
Drug: BRL 49653C
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo Controlled, Parallel Group Comparative Study to Evaluate the Efficacy and Safety of BRL 49653C With Concurrent Sulphonylurea Therapy, When Administered to Patients With Non-insulin Dependent Diabetes Mellitus.

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • 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. [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]

    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)



Secondary Outcome Measures:
  • 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. [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
    Physical examination, adverse experiences, laboratory safety data, ECG parameters


Enrollment: 77
Study Start Date: October 1998
Study Completion Date: April 2000
Primary Completion Date: April 2000 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BRL 49653C
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
BRL 49653C 2 mg bid or placebo bid through weeks 1 to 24.
Other Name: Avandia, rosiglitazone
Placebo Comparator: placebo
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01706211

Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 10002
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Study Chair: Lee-Ming Chuang, PHD National Taiwan University Hospital
  More Information

Publications:
Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01706211     History of Changes
Other Study ID Numbers: 49653/128
Study First Received: October 10, 2012
Last Updated: October 12, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
non insulin dependent diabetes mellitus, rosiglitazone

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

ClinicalTrials.gov processed this record on September 22, 2014