A 12-Week, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Dose Ranging Study to Evaluate the Efficacy, Safety and Tolerability of Denagliptin, Administered Orally, Once Daily, as Monotherapy in Subjects With Type 2 Diabetes Mellitus Followed by a 12-week Active Treatment Extension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 375
- 试验地点
- 1
- 主要终点
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
研究概览
简要总结
This is a 24-week study investigating the safety and efficacy of several dosages of a potential new oral medicine for Type II diabetes mellitus.
详细描述
A 12-Week, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Dose Ranging Study to Evaluate the Efficacy, Safety and Tolerability of GW823093, Administered Orally, Once Daily, as Monotherapy in Subjects With Type 2 Diabetes Mellitus followed by a 12-week Active Treatment Extension
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 75 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
- 未提供
研究组 & 干预措施
Placebo
Participants received oral dose of matching placebo capsule to denagliptin (DEN) once daily in the morning, 30 minutes (min) prior to breakfast during the main phase 12-weeks treatment period. Participants who were randomized to placebo in the main phase 12-weeks treatment period received oral dose of DEN 2.5 milligram (mg) once daily in the morning, 30 min prior to breakfast during the extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of placebo to the participants.
干预措施: Placebo (Drug)
DEN 2.5 mg
Participants received oral dose of DEN 2.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 2.5 mg to the participants.
干预措施: DEN 2.5 mg (Drug)
DEN 7.5 mg
Participants received oral dose of DEN 7.5 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 7.5 mg to the participants.
干预措施: DEN 7.5 mg (Drug)
DEN 15 mg
Participants received oral dose of DEN 15 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 15 mg to the participants.
干预措施: DEN 15 mg (Drug)
DEN 30 mg
Participants received oral dose of DEN 30 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 30 mg to the participants.
干预措施: DEN 30 mg (Drug)
DEN 45 mg
Participants received oral dose of DEN 45 mg capsule once daily in the morning, 30 min prior to breakfast during the main phase/extension phase 12-weeks treatment period. Participants were dispensed 3 bottles (bottle A, B and C) and were instructed to take 1 capsule daily from each bottle such that taking 1 capsule from each bottle daily provided the appropriate dose of DEN 45 mg to the participants.
干预措施: DEN 45 mg (Drug)
结局指标
主要结局
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
时间窗: Baseline (Week 0) and Week 12
HbA1c is used to show in participants with diabetes, how well their diabetes is being controlled. The HbA1c test gives the average blood glucose levels over the pervious two to three months. The sample for HbA1c assessment was collected at Visit 5 (Week 0) and Visit 12 (Week 12). Baseline value was defined as the assessment done at Week 0. The change from Baseline was calculated by subtracting the Baseline value (Week 0) from the individual post-Baseline (Week 12) value. Analysis of covariance (ANCOVA) model for analysis was used with the terms for gender, prior therapy (diet \& exercise/monotherapy), treatment, region and Baseline measurement (continuous covariate). Last observation carried forward (LOCF) dataset defined as carrying forward of the last valid observation recorded on-treatment (scheduled or unscheduled) for participants who withdrew from the study to all remaining main phase visits was used. Adjusted mean is reported as least square (LS) mean.
次要结局
- Change From Baseline in FPG at Week 12(Baseline (Week 0) and Week 12)
- Change From Baseline in FPG at Week 1, 2, 3, 4, 6, 8, 13, 14, 15, 16, 20 and 24(Baseline (Week 0) up to Week 24)
- Change From Baseline in HbA1c at Week 4, 8, 16, 20 and 24(Baseline (Week 0) up to Week 24)
- Number of Participants of FPG Responders at Week 12(Week 12)
- Number of Participants Who Were HbA1c Responders at Week 12(Week 12)
- Change From Baseline in Fasting Serum Insulin at Weeks 4, 8, 16, 20, 24 and Pro-insulin at Weeks 4 and 8(Baseline (Week 0) up to Week 24)
- Change From Baseline in Body Weight Over Time(Baseline (Week 0) and Week -5 to 25 (Follow-up))
- Mean Change From Baseline in Waist to Hip Ratio Over Time(Baseline (Week 0) up to Week 24)
- Population Pharmacokinetic (PK) Parameter of Plasma Concentration of DEN(Pre-dose at Week 0, 0.5 to 1.5 h post-dose at Week 4, 12, 16 or 20, 2 to 4 h post-dose at Week 4, 12, 16 or 20 and 6 to 10 h post-dose at Week 4, 12, 16 or 20)
- Change From Baseline in Fructosamine at Weeks 4, 8, 16, 20 and 24(Baseline (Week 0) up to Week 24)
- Change From Baseline in Pro-insulin to Insulin Ratio at Week 4 and 8(Baseline (Week 0) and Week 4 and 8)
- Number of Participants With Any Adverse Events (AE) or Serious Adverse Events (SAE) and Events of Hypoglycaemia(Up to Week 25)
- Number of Participants With AE and Event of Hypoglycaemia of Mild, Moderate and Severe(Up to Week 25)
- Change From Baseline in Waist Circumference and Hip Circumference Over Time(Baseline (Week 0) up to Week 24)
- Change From Baseline in Fructosamine at Week 12(Baseline (Week 0) and Week 12)
- Number of Participants With Laboratory Haematology Values of PCC at Any Time on Therapy(Up to Week 24)
- Change From Baseline in Fasting Serum Insulin and Pro-insulin at Week 12(Baseline (Week 0) and Week 12)
- Change From Baseline in Pro-insulin to Insulin Ratio at Week 12(Baseline (Week 0) and Week 12)
- Change From Baseline in Pro-insulin at Week 16, 20 and 24.(Baseline (Week 0) up to Week 24)
- Number of Participants With Change From Baseline Value of Potential Clinical Concern (PCC) in Vital Signs at Any Time During Therapy(Baseline (Week 0) up to Week 24)
- Number of Participants With Abnormal Urinalysis Dipstick Result(Up to Follow-up (Week 25))
- Number of Participants With Urinalysis Microscopic Result(Up to Follow-up (Week 25))
- Change From Baseline in Body Mass Index (BMI) Over Time(Baseline (Week 0) and Week -5 to 25 (Follow-up))
- Change From Baseline in 12-lead ECG Over Time(Baseline (Week 0) up to Week 24)
- Number of Participants With Laboratory Clinical Chemistry Values of PCC at Any Time on Therapy(Up to Week 24)
- Descriptive Statistics of Dipeptidyl Peptidase-IV (DPP-IV) Inhibition Performed as Part of the Population PK(Pre-dose at Week 0, 0.5 to 1.5 h post-dose at Week 4, 12, 16 or 20, 2 to 4 h post-dose at Week 4, 12, 16 or 20 and 6 to 10 h post-dose at Week 4, 12, 16 or 20)