A Multidose Study in Subjects With Type 2 Diabetes Mellitus to Assess the Pharmacokinetics and Pharmacodynamics of Albiglutide
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 283
- 试验地点
- 31
- 主要终点
- Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase
研究概览
简要总结
The first part of the study includes a single dose treatment period to evaluate the pharmacokinetic bioequivalence of a subcutaneous injection of albiglutide from process 2 drug substance compared with process 3 drug substance. The second part of the treatment period will evaluate additional pharmacokinetic and pharmacodynamic parameters and safety and tolerability of repeat doses of albiglutide given weekly for 12 weeks from process 2 drug substance compared with process 3 drug substance. Subjects with type 2 diabetes whose glycemia is inadequately controlled on their current regimen of diet and exercise or stable dose of metformin will be recruited into the study.
详细描述
This is a randomized, double-blind, multicenter, 2 parallel group study. The first part of the treatment period will evaluate the pharmacokinetic bioequivalence of a single dose of a subcutaneous injection of 30mg of albiglutide from process 2 drug substance compared with process 3 drug substance. The second part of the treatment period will evaluate additional pharmacokinetic parameters, pharmacodynamic parameters, immunogenicity, effects on glycosylated hemoglobin and fasting plasma glucose, and safety and tolerability of repeat doses of subcutaneous injections of 30mg of albiglutide given weekly for 12 weeks from process 2 drug substance compared with process 3 drug substance. Subjects with type 2 diabetes whose glycemia is inadequately controlled on their current regimen of diet and exercise or stable dose of metformin will be recruited into the study.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with a historical diagnosis of type 2 diabetes mellitus who are experiencing inadequate glycemic control on their current regimen of diet and exercise or on a stable dose of metformin
- •Body mass index ≥20 kg/m2 and ≤45 kg/m2
- •Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L)
- •Thyroid-stimulating hormone level is normal or clinically euthyroid
- •Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception.
排除标准
- •Current ongoing symptomatic biliary disease or history of pancreatitis
- •History of significant GI surgery
- •Recent clinically significant cardiovascular and/or cerebrovascular disease
- •History of human immunodeficiency virus infection
- •History of, or current hepatic disease
- •History of alcohol or substance abuse
- •Female subject is pregnant, lactating, or <6 weeks postpartum
- •History of type 1 diabetes
- •Receipt of any investigational drug within the 30 days, or 5 half-lives whichever is longer, before Screening or a history of receipt of an investigational antidiabetic drug within the 3 months before randomization, or receipt of any GLP-1 agents including albiglutide
- •History of, or family history of thyroid disease
结局指标
主要结局
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase
时间窗: Pre-dose at Baseline; 24 hours (hr), 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
To assess the bioequivalence of the two formulations of albiglutide, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter AUC(0-inf) estimated from the BE Phase. AUC is a measure of how much albiglutide is in the blood at certain time points. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase
时间窗: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose
To assess the bioequivalence of the two formulations of study drug, an analysis of variance (ANOVA) model with treatment as a fixed effect was applied to the natural-log-transformed parameter Cmax estimated from the BE phase. The Process 2 treatment group (albiglutide derived from process 2) was the reference group and was compared with the Process 3 treatment group (albiglutide derived from process 3) as the test group (i.e., treatment comparisons based on the ratio of Process 3:Process 2). Blood samples for pharmacokinetic analysis were collected prior to dosing at Baseline and 24 hours (hr), 48 hr, 96 hr, 120 hr, 216 hr, 312 hr, 480 hr, and 672 hr after administration of the Baseline study medication.
次要结局
- Cmax of Albiglutide in the BE Phase(Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose)
- Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit(Week 1 through Week 25)
- Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase(Baseline, Week 5, Week 9, Week 13, Week 17, and Week 25 (Follow-up))
- AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase(Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose)
- Number of Participants With Indicated Adverse Events of Special Interest(From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinue active participation in the study)
- Tmax and Tlag of Albiglutide in the BE Phase(Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose)
- t1/2 of Albiglutide in the BE Phase(Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose)
- Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase(Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose)
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17(Baseline and Week 17)
- Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP)(Immediately pre-dose at Week 5, Week 9, Week 13, Week 17 (End of Treatment [EOT]), and Week 25 (Follow-up))
- Apparent Clearance of Albiglutide in the BE Phase(Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17(Baseline and Week 17)
- Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit(Week 1 through Week 25)
- Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit(Week 1 through Week 25)
- Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)(From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinued active participation in the study)
- Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17(Screening and Week 17)