A Phase 1, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Escalating Oral Doses of PF-07081532 in Adult Participants 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
- 66
- 试验地点
- 2
- 主要终点
- Number of Participants With Vital Signs Abnormalities
研究概览
简要总结
This is a randomized, placebo-controlled, double-blind (investigator- and participant-blinded), sponsor-open, dose-escalating study of PF-07081532 in patients with Type 2 diabetes on metformin (Parts A and C). The study may also enroll non-diabetic participants with obesity (Part B). Study participants will receive an investigational product or placebo every day for up to 28 days (Part A) or up to 42 days (Part B, optional; Part C, optional).
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple oral doses of PF-07081532 in participants with inadequately controlled T2DM on metformin and optionally in non-diabetic obese participants.
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)
盲法说明
double-blind (investigator- and participant-blind), sponsor-open
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
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Active Obesity
Part B
干预措施: Placebo (Other)
Active Obesity
Part B
干预措施: Clopidogrel (Drug)
Placebo T2DM
Parts A and C
干预措施: PF-07081532 (Drug)
Placebo Obesity
Part B
干预措施: Placebo (Other)
Placebo Obesity
Part B
干预措施: Clopidogrel (Drug)
Active T2DM
Parts A and C
干预措施: PF-07081532 (Drug)
结局指标
主要结局
Number of Participants With Vital Signs Abnormalities
时间窗: From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)
Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in vital signs, were supine systolic blood pressure \< 90 millimeters of mercury (mmHg), supine systolic blood pressure increase/decrease from baseline ≥ 30mmHg; supine diastolic blood pressure \<50 mmHg, supine diastolic blood pressure increase/decrease from baseline ≥ 20mmHg; pulse rate \<40 beats per minute (bpm) or \>120 bpm.
Number of Participants With Treatment Emergent Treatment-Related Adverse Events
时间窗: From the first dose up to 28-35 days after last administration of study intervention (that is a maximum of 63 days from first dose for Part A and a maximum of 77 days from first dose for Part B and Part C)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Laboratory Abnormalities
时间窗: From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)
Participants with laboratory abnormalities with ≥2 occurrences (without regard to baseline abnormality) that met pre-specified criteria were High-density lipoprotein (HDL) Cholesterol \<0.8✕ lower limit of normal (LLN); Bicarbonate \<0.9✕LLN; Calcitonin\>1.0✕upper limit of normal (ULN); Triglycerides \>1.3✕ULN; Aspartate Aminotransferase \>3.0✕ULN; Low-density lipoprotein (LDL) Cholesterol \>1.2✕ULN; Urine Glucose ≥1; Urine Ketones ≥1; Urine Leukocyte Esterase ≥1; Urine Leukocytes ≥20; Urine Hyaline Casts \>1; Urine Hemoglobin ≥1; and Urine Nitrite ≥1.
Number of Participants With Abnormal Electrocardiogram (ECG)
时间窗: From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)
The pre-specified categorical analysis criteria in ECG, were PR interval: value ≥ 300 milliseconds (msec), percentage change ≥ 25/50%; QRS duration: value ≥140 msec, percentage change ≥ 50%; QTcF interval: 450 \< value ≤ 480 msec, 480 \< value ≤ 500 msec, value \>500 msec, and 30\<change ≤ 60 msec, change \>60 msec.
次要结局
- Area Under the Curve From Time 0 to 24 Hours (AUC24) Post Dose for PF-07081532(0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C)
- Cumulative Amount of Drug Recovered Unchanged in Urine Over 24 Hours (Ae24) for PF-07081532(Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours))
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-07081532(0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C)
- Time Measured for the Plasma Concentration to Decrease by One-Half (t1/2) for PF-07081532(0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 28 for Part A, on Day 42 for Part B and Part C)
- Maximum Observed Plasma Concentration (Cmax) for PF-07081532(0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C)
- Percentage of Ae24 (Ae24%) for PF-07081532(Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours))
- Renal Clearance (CLr) for PF-07081532(Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours))