NCT00500331已完成2 期
A Double-blind, Randomized 12-week Study to Evaluate the Safety and Efficacy of GSK189075 Tablets vs Pioglitazone in Treatment Naive Subjects With Type 2 Diabetes Mellitus
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 334
- 试验地点
- 1
- 主要终点
- Change From Baseline (Week 0) in Glycosylated Hemoglobin (HbA1c) (%) at Week 12
研究概览
简要总结
This is a dose-ranging study that will evaluate the efficacy, safety and tolerability of a range of doses of investigational product and pioglitazone, compared to placebo, administered as monotherapy over 12 weeks in treatment naive patients with T2DM
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Metabolic Disease
- •Diagnosis of Type 1 diabetes mellitus.
- •History of ketoacidosis which has required hospitalization.
- •Thyroid disorder [TSH below the lower limit of the reference range (LLRR) of 0.4mIU/L or above the upper limit of the reference range (ULRR) of >5.5 mIU/L at Screening]. Hypothyroidism treated with the same dose and regimen of thyroid hormone replacement for at least 3 months prior to Screening is allowed.
- •BMI of <22 or >43 kg/m
- •Significant weight gain or loss (as defined as >5% of total body weight) in the 3 months prior to Screening.
- •Diabetic Medication
- •Has taken insulin or any oral or injectable anti-diabetic medication ≥4 weeks at any time prior to screening.
- •Has taken insulin or any oral or injectable anti-diabetic medication within 3 months of screening.
- •Cardiovascular Disease
- •Recent history or presence of clinically significant acute cardiovascular disease including:
- •Documented myocardial infarction in the 6 months prior to Screening.
- •Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery either planned and/or occurred in the 6 months prior to Screening.
- •Unstable angina in the 6 months prior to Screening.
- •Clinically significant supraventricular arrhythmias requiring medical therapy, or history of nonsustained or sustained ventricular tachycardia. Symptomatic valvular heart disease or valvular heart disease requiring therapy other than endocarditis prophylaxis.
- •Congestive heart failure (CHF, New York Heart Association (NYHA) Class II to IV) requiring pharmacologic treatment. NYHA Class I may be included in accordance with the local prescribing information for pioglitazone.
- •Blood pressure (BP) >150/100mmHg. If a subject is receiving permitted antihypertensive therapy, then they must be on stable dose(s) of therapy for at least 4 weeks prior to Screening.
- •Has a QTc interval (Bazett's) ≥450msec at Screening on a single ECG or an average value from 3 ECGs taken 5 minutes apart (on local reading of ECG).
- •Other clinically significant ECG abnormalities which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity.
- •Fasting triglycerides ≥400mg/dL (4.56mmol/L) at Screening. If a subject is receiving permitted lipid-lowering therapy, then they must be on a stable dose(s) of therapy for at least 6 weeks prior to Screening. Niacin and bile acid sequestrants are prohibited.
- •Hepatic Disease
- •Has a diagnosis of active hepatitis (hepatitis B surface antigen or hepatitis C antibody), or clinically significant hepatic enzyme elevation including:
- •Any one of the following enzymes greater than 2 times the upper limit of the reference range (ULRR) value at Screening.
- •alanine transaminase (ALT).
- •aspartate transaminase (AST).
- •alkaline phosphatase (AP). Has a total bilirubin level that is >1.5 times the ULRR at Screening with the exception of suspected or confirmed Gilbert's disease.
- •Pancreatic Disease
- •Secondary causes of diabetes:
- •history of chronic or acute pancreatitis
- •Renal Disease
- •Significant renal disease at Screening as manifested by:
- •Glomerular filtration rate (GFR) <60mL/min (as estimated from serum creatinine at Visit 1 and demographic data using the MDRD equation).For the MDRD equation, please refer to the study procedures manual.
- •Proteinuria of ≥1+ by urinary dipstick
- •Recurrent genitourinary tract infections defined as ≥2 episodes of complicated or uncomplicated cystitis or pyelonephritis in the 6 months prior to Screening
- •A positive qualitative urinary dipstick for leukocytes, red blood cells (RBC) or nitrites at Screening.
- •Concurrent Disease
- •Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests (including blood electrolytes), electrocardiogram, including pulmonary, neurological or inflammatory diseases, which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise contraindicates participation in a clinical trial with a new chemical entity
- •History of significant co-morbid diseases active in the 6 months prior to Screening (e.g., cholecystitis, acute pancreatitis, gastrointestinal disease, chronic diarrhea, etc.)
- •Has a history of malignancy within the past five years [other than superficial squamous cell carcinoma which is non-invasive on pathology or basal cell carcinoma which is successfully treated with local excision] and cervical cancer in situ treated definitively at least 6 months prior to Screening
- •Concurrent Medication
- •Is currently taking or has taken any of the following medications in the 8 weeks prior to Screening:
- •Warfarin and other oral anticoagulants (aspirin and non-steroidal anti-inflammatory drugs are permitted)
- •Bile acid sequestrants
- •Niacin (excluding routine vitamin supplementation)
- •Antiobesity agents (including fat absorption blocking agents)
- •Oral or injectable corticosteroids (inhaled and intranasal corticosteroids are permitted)
- •Loop diuretics
- •Monoamine oxidase inhibitors and tricyclic amines
- •Antiretroviral drugs
- •St John's Wort
- 另有 10 项未显示
研究组 & 干预措施
Arm 1
Experimental
GSK189075
干预措施: GSK189075 (Drug)
Arm 2
Placebo Comparator
Placebo
干预措施: Placebo (Other)
Arm 3
Other
pioglitazone (active control)
干预措施: pioglitazone (Drug)
结局指标
主要结局
Change From Baseline (Week 0) in Glycosylated Hemoglobin (HbA1c) (%) at Week 12
时间窗: Baseline (Week 0) and Week 12
Fasted blood samples for HbA1c were collected at Baseline and Week 12. Participants were required to fast for at least 8 hours prior to laboratory samples and were told not to take the morning dose of study medication on these visit days and to refrain from eating until instructed to do so by study personnel in the clinic. When the participant had not fasted, the participant was rescheduled to return to the clinic to have a fasted sample taken. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Only those participants with a value at Baseline and at Week 12 (after Last Observation Carried Forward \[LOCF\]) were used for this analysis. Adjusted mean is presented as least square mean.
次要结局
- Change From Baseline in 24-hour Percent of Filtered Glucose Excreted in Urine(Baseline (Week 0) and Week 12 (24-hour urine collection))
- Change From Baseline in HbA1c (%) at Weeks 4 and 8(Baseline (Week 0) and Week 4 and Week 8)
- Number of Participants With On-therapy Hypoglycemia(Up to 14 weeks)
- Change From Baseline to Week 12 in Fasting Plasma Glucose (FPG) at Weeks 4, 8 and 12(Baseline (Week 0) and Week 4, Week 8 and Week 12)
- Change From Baseline to Week 12 in Fructosamine(Baseline (Week 0) to Week 12)
- Change From Baseline to Week 12 in Fasting Insulin(Baseline (Week 0) to Week 12)
- Number of Participants at Week 12 With: HbA1c <= 6.5%, HbA1c <7.0%; FPG <7 Mmo/L, FPG <7.8 mmol/L; FPG <5.5 mmol/L; a Decrease From Baseline of HbA1c >= 0.7%; a Decrease From Baseline of FPG ≥1.7 mmol/L(Week 12)
- Change From Baseline to Week 12 in Body Weight(Baseline (Week 0) to Week 12)
- Change From Baseline to Week 12 in Waist Circumference(Baseline (Week 0) to Week 12)
- Change From Baseline in Insulin AUC During a 2-hour OGTT(Baseline (Week 0) and Week 12 (0 to 2-hour OGTT))
- Percent Change From Baseline in Lipid Parameters at Weeks 4, 8 and 12(Triglycerides [TG], Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C] and High-density Lipoprotein Cholesterol [HDL-C])(Baseline (Week 0) and Week 4, Week 8 and Week 12)
- Number of Participants With Change From Baseline Vital Signs of Potential Clinical Concern(Up to 14 weeks)
- Number of Participants With Change From Baseline in Standard Laboratory Parameters of Potential Clinical Concern(Up to 14 weeks)
- Change From Baseline in Plasma Glucose Area Under the Curve (AUC) During a 2-hour Oral Glucose Tolerance Test (OGTT)(Baseline (Week 0) and Week 12 (0 to 2 hour OGTT))
- Change From Baseline in C-peptide AUC During a 2-hr OGTT(Baseline (Week 0) and Week 12 (0 to 2 hour OGTT))
- Number of Participants With On-therapy Adverse Events (AE) and Serious Adverse Events (SAE)(Up to 12 weeks)
- Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Concern(Up to Early withdrawal (Between Week 12 and Week 14))
研究者
研究点 (1)
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