A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF MULTIPLE ESCALATING ORAL DOSES OF PF-06882961 IN ADULT 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
- 98
- 试验地点
- 4
- 主要终点
- Number of Participants With All-causality and Treatment-related Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a dose-escalating study in patients with Type 2 diabetes on metformin. Participants will receive an investigational product or placebo for 28 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Type 2 diabetes treated with a stable dose of metformin at least 500 mg
- •HbA1c value between 7.0 and 10.5%
排除标准
- •Type 1 diabetes or secondary forms of diabetes
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
PF-06882961 30 mg
干预措施: PF-06882961 (Drug)
PF-06882961 100 mg
干预措施: PF-06882961 (Drug)
PF-06882961 300 mg
干预措施: PF-06882961 (Drug)
PF-06882961 600 mg
干预措施: PF-06882961 (Drug)
PF-06882961 dose TBD Cohort 5
干预措施: PF-06882961 (Drug)
PF-06882961 dose TBD Cohort 6
干预措施: PF-06882961 (Drug)
PF-06882961 dose TBD Cohort 7
干预措施: PF-06882961 (Drug)
PF-06882961 dose TBD Cohort 8
干预措施: PF-06882961 (Drug)
结局指标
主要结局
Number of Participants With All-causality and Treatment-related Treatment-emergent Adverse Events (TEAEs)
时间窗: From baseline to up to 35 days after last dose for a total of approximately 63 days
Treatment-related adverse event (AE) was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent.
Number of Participants With Abnormal Electrocardiogram (ECG) Interval
时间窗: From baseline to up to 14 days after last dose for a total of approximately 42 days
ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (\>=) 300 millisecond (msec), b) \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec. 2. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) \>=140 msec, b) \>=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and \<=480 msec, b) \>480 msec and \<=500 msec, c) \>500 msec, d) \>30 msec and \<=60 msec increase from baseline, e) \>60 msec increase from baseline
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality
时间窗: From baseline to up to 14 days after last dose for a total of approximately 42 days
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time \[PT\], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin).
Number of Participants With Abnormal Vital Signs
时间窗: From baseline to up to 14 days after last dose for a total of approximately 42 days
Vital signs categorical summarization criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (\>=) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP \>= 20 mmHg.
次要结局
- AUC24 and AUCtau of PF-06882961 on Day 1, Day 14 or 21 and Day 28(0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28)
- Amount of Unchanged Drug Recovered in Urine Over 24 Hours (Ae24) of PF-06882961 on Day 28(0 to 24 hours post-dose on Day 28)
- Ae24 (%) of PF-06882961 on Day 28(0 to 24 hours post-dose on Day 28)
- Renal Clearance (CLr) of PF-06882961 on Day 28(0 to 24 hours post-dose on Day 28)
- Maximum Plasma Concentration (Cmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28(0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1, 14 or 21, and 28)
- Time for Cmax (Tmax) of PF-06882961 on Day 1, Day 14 or 21 and Day 28(0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 1, 14 or 21, and 28)
- Terminal Half-life (t½) of PF-06882961 on Day 28(0, 1, 2, 4, 6, 8, 10, 12, 14 and 24 hrs post dose on Day 28)
