A Phase 1 Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of PF-04971729 After Administration of Single Escalating Oral Doses Under Fed and Fasted Conditions in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Number of Participants Experiencing an Adverse Event (AE)
研究概览
简要总结
Ertugliflozin (PF-04971729, MK-8835) is a new compound proposed for the treatment of Type 2 diabetes mellitus. The primary purpose of this study is to evaluate the safety and tolerability along with the pharmacokinetics of single escalating doses of ertugliflozin under fed and fasted conditions in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and/or female subjects of non childbearing potential.
- •Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
研究组 & 干预措施
Cohort 1 Sequence 1
Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Ertugliflozin (Drug)
Cohort 1 Sequence 1
Period 1 (fasted) Placebo → Period 2 (fasted) ertugliflozin (E) 10 mg → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Placebo to Ertugliflozin (Drug)
Cohort 1 Sequence 2
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Ertugliflozin (Drug)
Cohort 1 Sequence 2
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 100 mg → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Placebo to Ertugliflozin (Drug)
Cohort 1 Sequence 3
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Ertugliflozin (Drug)
Cohort 1 Sequence 3
Period 1 (fasted) E 0.5 mg → Period 2 (fasted) E 10 mg → Period 3 (fasted) Placebo → Period 4 (fed) E 100 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Placebo to Ertugliflozin (Drug)
Cohort 2 Sequence 1
Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Ertugliflozin (Drug)
Cohort 2 Sequence 1
Period 1 (fasted) Placebo → Period 2 (fasted) E 30 mg → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Placebo to Ertugliflozin (Drug)
Cohort 2 Sequence 2
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Ertugliflozin (Drug)
Cohort 2 Sequence 2
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) Placebo → Period 3 (fasted) E 300 mg. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Placebo to Ertugliflozin (Drug)
Cohort 2 Sequence 3
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Ertugliflozin (Drug)
Cohort 2 Sequence 3
Period 1 (fasted) E 2.5 mg → Period 2 (fasted) E 30 mg → Period 3 (fasted) Placebo. Each dose of study drug will be separated by a minimum of 7 days.
干预措施: Placebo to Ertugliflozin (Drug)
结局指标
主要结局
Number of Participants Experiencing an Adverse Event (AE)
时间窗: Up to Day 10 of each dosing period
Number of Participants Discontinuing Study Drug Due to an AE
时间窗: Up to Day 8 of each dosing period
Change from baseline in 24-hour urinary glucose excretion
时间窗: Baseline and 24 hours
Area under the plasma concentration-time curve (AUC) from Time 0 to infinity (AUCinf) for ertugliflozin
时间窗: Up to Day 4 of each treatment period
Area under the plasma concentration-time curve (AUC) from Time 0 to time of the last quantifiable concentration (AUClast) for ertugliflozin
时间窗: Up to Day 4 of each treatment period
Maximum plasma concentration (Cmax) of ertugliflozin
时间窗: Up to Day 4 of each treatment period
Time taken to reach the maximum observed plasma concentration (Tmax) of ertugliflozin
时间窗: Up to Day 4 of each treatment period
Ertugliflozin half life (t1/2)
时间窗: Up to Day 4 of each treatment period
Apparent clearance (CL/F) after a single dose of ertugliflozin
时间窗: Up to Day 4 of each treatment period
Apparent volume of distribution (Vz/F)
时间窗: Up to Day 4 of each treatment period
次要结局
- Urinary glucose excretion over 72 hours(Up to 72 hours of each dosing period)
- Change from baseline in 24-hour weighted mean glucose(Baseline and 24 hours)
- Inhibition of glucose reabsorption(Up to 24 hours of each dosing period)
- Renal clearance (CLr) of Ertugliflozin(Up to 24 hours of each dosing period)
- Urinary recovery of Ertugliflozin(Up to 24 hours of each dosing period)