A Phase 1 Double-blind, Placebo-controlled, Randomized, Single- And Multiple-ascending Dose Study To Assess The Safety, Tolerability, And Pharmacokinetics Of Pf-06293620 In Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 84
- 试验地点
- 14
- 主要终点
- Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events
研究概览
简要总结
A first in human study to determine the safety, tolerability and pharmacokinetics of single and multiple ascending doses of PF-06293620 in subjects with Type 2 Diabetes Mellitus
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Men and women of non-childbearing potential with Type 2 Diabetes Mellitus
- •Subjects on stable doses of metformin >/= 1500 mg daily (SAD cohorts) or >/= 1000 mg daily (MAD cohorts) x 30 days prior to screening
- •HbA1c 7-10% (SAD Cohorts) or 6.5-10% (MAD cohorts) inclusive at screening
- •Fasting C-peptide >1.12 ng/mL (SAD cohorts) or >/= 0.8 mg/mL (MAD cohorts) at screening
排除标准
- •History of Type 1 diabetes mellitus
- •Evidence of diabetic complications with significant end-organ damage
- •History of chronic pancreatitis or at high risk for pancreatitis
- •Poorly controlled hypertension
- •History of cardiovascular or cerebrovascular event or procedure
结局指标
主要结局
Number of Participants With All-Causality and Treatment Related Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events
时间窗: Days 1 to 85 for SAD cohorts and Days 1 to 169 for MAD cohorts; participants with positive anti-drug antibody (ADA) results were followed up to stabilization of ADA titers or up to 9 months after Day 169 visit.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study drug and up to Day 85 (for SAD cohorts) or Day 169 (for MAD cohorts) that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs. Causality with the study treatment was determined by the investigator.
Number of Participants With Dose Limiting or Intolerable Adverse Events
时间窗: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts
Dose limiting or intolerable AEs were originally planned to be collected. However, this outcome measure was not actually summarized, since collection and monitoring of treatment-emergent AEs was performed during the study, and deemed sufficient to ensure the participants safety.
Number of Participants With Positive Anti-drug Antibody (ADA) Result
时间窗: Days 1 to 85 for SAD cohorts; Days 1 to 169 for MAD Cohorts
ADA against PF-06293620 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer \>=1.88 was considered positive.
次要结局
- Area Under the Serum Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Apparent Volume of Distribution (Vz/F) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Time for Maximum Serum Concentration (Tmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Clearance (CL) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Time for Maximum Serum Concentration (Tmax) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06293620 (MAD Cohorts) After Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Apparent Volume of Distribution (Vz/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Dose-normalized AUCinf (AUCinf(dn)) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Steady-state Volume of Distribution (Vss) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Average Concentration (Cav) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Terminal Elimination Half-life (Thalf) of PF-06293620 (MAD Cohorts) After Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Area Under the Serum Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Dose-normalized AUClast (AUClast(dn)) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Apparent Clearance (CL/F) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Maximum Serum Concentration (Cmax) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Apparent Clearance (CL/F) of PF-06293620 (MAD Cohorts) After Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Observed Accumulation Ratio Based on Cmax (Rac,Cmax) of PF-06293620 (MAD Cohorts)(Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Terminal Elimination Half-life (Thalf) of PF-06293620 (SAD Cohorts)(Pre-dose, 1, 4, 8 and 12 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; Days 3, 4, 5, 8, 15, 22, 29, 43, 57, 85)
- Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Maximum Serum Concentration (Cmax) of PF-06293620 (MAD Cohorts) After Day 1 and Day 57 Administration(Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)
- Observed Accumulation Ratio Based on AUC (Rac) of PF-06293620 (MAD Cohorts)(Pre-dose, 1 and 4 hours post-dose on Day 1; Days 2, 3, 7, 8, 15, 27, 28; pre-dose, 1 and 4 hours post-dose on Day 29; Days 36, 43; pre-dose, 1 and 4 hours post-dose on Day 57; Days 58, 59, 63, 64, 71, 78, 84, 85, 99, 113, 141, 169)