A Phase 1, Placebo-Controlled Randomized Trial To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Ascending Intravenous Doses Of PF-05231023 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
- 50
- 试验地点
- 1
- 主要终点
- Number of Participants With Abnormal Physical Examination Findings
研究概览
简要总结
This is a trial in subjects with Type 2 diabetes mellitus to study the safety, tolerability and pharmacokinetics of multiple ascending doses of PF-05231023.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male subjects and female subjects of non-childbearing potential between the ages of 30 and 70 years, inclusive, with a historical diagnosis of type 2 diabetes mellitus, diagnosed according to the American Diabetes Association guidelines. Subjects who have other conditions but are well controlled by either diet or medications may be included as well (for example, a subject with high cholesterol level on appropriate treatment is eligible).
- •Body Mass Index (BMI) of 25 to 35.5 kg/m2, and a total body weight >50 kg (110 lbs).
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).
- •Diagnosis of Type 1 diabetes mellitus.
- •Evidence of diabetic complications with significant end organ damage
研究组 & 干预措施
Treatment
干预措施: PF-05231023 (Drug)
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Abnormal Physical Examination Findings
时间窗: Baseline up to Day 42
Physical examination included assessment of height, weight, blood pressure, pulse rate and body temperature. Criteria for abnormal physical findings was based on investigator's discretion and were reported as adverse event (AE), as planned.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: Baseline up to Day 77
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 77 which were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Abnormal Laboratory Values
时间窗: Baseline up to Day 42
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (RBCs)(less than \[\<\] 0.8\*lower limit of normal\[LLN\]); leucocytes (\<0.6/greater than \[\>\]1.5\*upper limit of normal \[ULN\]); platelets (\<0.5\*LLN\>\</0\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\*LLN\>\</0\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); total bilirubin, direct bilirubin, indirect bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (\>3\*ULN), total protein, albumin (\<0.8\*LLN\>\</0\>1.2\*ULN); creatinine, urea (\>1.3\*ULN); glucose (\<0.6\*LLN\>\</0\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN\>\</0\>1.1\*ULN); urine RBCs, urine white blood cells (WBCs) (\> or equal\[=\]20 high-powered field), urine bacteria \>20 high-powered field. Total number of participants with any laboratory abnormalities were reported.
Number of Participants With Vital Signs Abnormalities
时间窗: Baseline up to Day 77
Criteria for vital signs abnormalities: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mm Hg), supine diastolic BP (DBP) \<50 mm Hg, supine pulse rate \<40 beats per minute (bpm), \> 120 bpm. Maximum increase or decrease from baseline in supine SBP \>=30 mm Hg and maximum increase or decrease from baseline in supine DBP \>=20 mm Hg.
Number of Participants With Electrocardiogram (ECG) Abnormalities
时间窗: Baseline up to Day 77
Criteria for potential clinical concern in ECG parameters: maximum PR interval of greater than or equal to (\>=) 300 milliseconds (msec), maximum QRS interval \>=140 msec, maximum QTCF interval (Fridericia's Correction) of 450 to \<480 msec, 480 to \<500 msec and \>=500 msec, maximum increase of \>=25 percent (%) for baseline value of \>200 msec and \>=50% for baseline value of less than or equal to (\<=) 200 msec for PR interval, maximum increase from baseline of \>=50% for QRS interval, maximum increase from baseline of \>=30 msec to \<60 msec and maximum increase from baseline of \>60 msec in QTCF interval (Fridericia's Correction).
Number of Participants With Blood Glucose Abnormalities
时间窗: Baseline up to Day 32
Criteria for blood glucose abnormality: Blood glucose levels \<0.6\* LLN or \>1.5\* ULN.
次要结局
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 After Single Dose(0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 After Single Dose(0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3)
- Maximum Observed Plasma Concentration (Cmax) of PF-05231023 After Single Dose(0 hour (pre-dose) on Day 1, 4; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1; Day 2, 3)
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Apparent Clearance (CL) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Volume of Distribution of PF-05231023 at Steady State (Vss)(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Minimum Observed Plasma Trough Concentration (Cmin) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Average Plasma Concentration (Cav) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Maximum Observed Plasma Concentration (Cmax) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)
- Accumulation Ratio for Area Under the Curve From Time Zero to End of Dosing Interval of PF-05231023 (Rac)(0 hour (pre-dose) on Day 1, 4, 25; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1, 25; Day 2, 3, 26, 29)
- Accumulation Ratio for Maximum Observed Plasma Concentration (Rac,Cmax) of PF- 05231023(0 hour (pre-dose) on Day 1, 4, 25; 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 1, 25; Day 2, 3, 26, 29)
- Plasma Terminal Half-Life (t1/2) of PF-05231023 at Steady State(0 hour (pre-dose) 0.5, 1 (end of infusion), 1.5, 2, 3, 5, 9, 13 hours post-start of infusion on Day 25; Day 26, 29)