Clinical trial NCT01453049: An Efficacy and Safety Study of Fixed-dose Rosiglitazone/Glimepiride to Treat Chinese Type 2 Diabetes Patients
Official title: A Multi-center, Randomized, Double-blind, Parallel-group Study to Compare the Efficacy and Safety of Fixed-dose Rosiglitazone/Glimepiride Combination Therapy With Glimepiride Monotherapy for 24 Weeks in Drug Naive Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: rosiglitazone/glimepiride, fix dose, type 2 diabetes
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to demonstrate that the rosiglitazone/glimepiride fixed-dose combination tablet will safely and effectively control glycemia as first-line oral therapy in drug naïve subjects with type 2 diabetes. This 24-week study will compare the effects of treatment with rosiglitazone/glimepiride to treatment with glimepiride alone. The primary objective is to demonstrate superiority of rosiglitazone/glimepiride to glimepiride in lowering Glycosylated Hemoglobin (HbA1c).

Detailed description: The antihyperglycemic effect of the thiazolidinedione (TZD) class of oral antidiabetic agents is due to their ability to increase insulin sensitivity at the cellular level, which in turn improves the ability of endogenous insulin to regulate glucose utilization by the tissues. Compounds of the sulfonylurea (SU) class act to stimulate insulin production by the pancreas, overcoming insulin resistance by increasing circulating insulin levels. The mechanisms of two kind OADs may be viewed as complementary, offering the opportunity for improved efficacy and durability of effect through coadministration of a TZD and a sulfonylurea.

Successful management of type 2 diabetes mellitus (T2DM) requires aggressive glycemic control starting at the earliest stages of the disease. Rosiglitazone/glimepiride combination therapy, with complementary mechanisms of action, has the potential to provide significant benefits over monotherapy as first line therapy. Treatment with rosiglitazone/glimepiride at this early stage of diabetes is expected to provide better glycemic control and allow a greater proportion of patients to achieve target glycemic goals than oral monotherapy.

This was a multicenter, randomized, double-blinded, parallel, study to compare the effects of treatment with rosiglitazone/glimepiride combination or glimepiride in drug naïve T2 DM patients.

Eligibility criteria: Inclusion Criteria:

* type 2 diabetes mellitus
* HbA1c between 7.5% and 11.0% at screening
* FPG between 7.0mmol/L and 13.3mmol/L at screening and at randomization visit
* subject was treated with diet and/or exercise alone
* QTc\<450mesc or QTc\<480msec for patients with bundle branch block
* Body Mass Index (BMI) \>19kg/m2
* Subject has given written informed consent

Exclusion Criteria:

* Documented history of significant hypersensitivity to thiazolidinediones, sulfonylureas, or compounds with similar chemical structures
* Ongoing edema or history of edema requiring pharmacological treatment in the 12 months prior to screening
* Presence of ischemic heart disease and/or peripheral arterial disease, or NYHA grade I-IV congestive heart failure
* Taking nitrates
* Clinically significant renal or hepatic disease
* Anemia
* Severe hypertriglyceridemia (TG\>=5.65mmol/L)
* Use of oral corticosteroids and Nicotinic acid
* Systolic blood pressure \<170mmHg, or diastolic blood pressure \> 100mmHg while on anti-hypertensive treatment
* Hyperthyroidism requiring treatment
* Diagnosed macular edema
* Women who are lactating, pregnant, or planning to become pregnant
* Presence of an active cancer or recently treated for cancer
* Drug/alcohol abuse
* Unwilling or unable to comply with the procedures described in the protocol

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24
timeFrame: Baseline (Week 0) and Week 24
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Number of HbA1c Responders and Non-responders
timeFrame: Baseline (Week 0) and Week 24 (LOCF)
measure: Number of FPG Responders and Non-responders
timeFrame: Baseline (Week 0) and Week 24 (LOCF)
measure: Number of Participants Who Achieved HbA1c <7%, HbA1c <=6.5%, or Who Achieved a Decrease of >=0.7% From Baseline
timeFrame: Baseline (Week 0) and Week 24 (LOCF)
measure: Change From Baseline in Fasting Proinsulin and Insulin at Week 24/Early Withdrawal (EW)
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Homeostasis Model Assessment Sensitivity (HOMA-S) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Homeostasis Model Assessment Beta-cell Function (HOMA-B) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Number of Participants at Various Dose Levels at Week 24/EW
timeFrame: Week 24/EW
measure: Change From Baseline in Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C), Low Density Lipoprotein-cholesterol (LDL-C), and Triglyceride (TG) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Blood Urea Nitrogen (BUN), Sodium, Potassium, Chloride, Calcium, and Phosphorus at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in the Ratio of TC/HDL-C and LDL-C/HDL-C at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in High Sensitivity C-reactive Protein (Hs-CRP) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Percent Change From Baseline in High Sensitivity C-reactive Protein (Hs-CRP) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Adjusted Diabetes Quality of Life (A-DQOL) Scores at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Number of Participants With Hypoglycemic Events
timeFrame: Week 24/EW
measure: Number of Hypoglycemic Events
timeFrame: Week 24/EW
measure: Number of Participants With a Bone Fracture
timeFrame: Week 24/EW
measure: Change From Baseline in White Blood Cell (WBC) Count and Platelet Count at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Red Blood Cell (RBC) Count at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Lymphocytes, Monocytes, Neutrophils, Eosinophils, and Basophils at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Hematocrit (HCT) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Hemoglobin (HE), Mean Corpuscular Hemoglobin Concentration (MCHC), Total Protein (TP), and Albumin at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Mean Corpuscular Volume (MCV) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Mean Corpuscular Hemoglobin (MCH) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT), Lactate Dehydrogenase (LDH), Alkaline Phosphatase (ALP), and Creatine Kinase (CK) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Total Bilirubin (TB), Direct Bilirubin (DB), Creatinine, and Uric Acid (UC) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Heart Rate at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Weight at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Electrocardiogram (ECG) Assessment of Heart Rate at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
measure: Change From Baseline in Electrocardiogram (ECG) Data at Week 24/EW
timeFrame: Baseline (Week 0) and Week 24/EW
Other outcomes:
Locations:
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Suzhou
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Dalian
country: China
facility: GSK Investigational Site
state: Liaoning
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Hangzhou
country: China
facility: GSK Investigational Site
state: Zhejiang
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Chongqing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shenyang
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
city: Wuhan
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: