A Phase 1, Double-blind, Placebo-controlled, Randomized, Parallel Group Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-04856883 In Adult Female 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 Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG)
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of PF-04856883 (CVX-096) in adult female subjects with Type 2 diabetes mellitus on high dose of metformin.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •History of Type 2 diabetes and currently being treated with high dose metformin
- •BMI between 22.0 and 40.0 kg/m2
- •HbA1c between 7.0-10.0%
- •Fasting C-peptide >1.21 ng/mL
排除标准
- •History of clinically significant chronic conditions other than Type 2 diabetes not well controlled by either diet or medications
- •Treatment with anti-diabetic therapies other than metformin
- •History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody
- •Males or women of childbearing potential
研究组 & 干预措施
Treatment Arm 7 (Stage 1B)
干预措施: PF-04856883 (Biological)
Treatment Arm 12 (Stage 2)
干预措施: PF-04856883 (Biological)
Treatment Arm 10 (Stage 2)
干预措施: PF-04856883 (Biological)
Treatment Arm 9 (Stage 2)
干预措施: Placebo (Biological)
Treatment Arm 11 (Stage 2)
干预措施: PF-04856883 (Biological)
Treatment Arm 5 (Stage 1B)
干预措施: Placebo (Biological)
Treatment Arm 1 (Stage 1A)
干预措施: Placebo (Biological)
Treatment Arm 2 (Stage 1A)
干预措施: PF-04856883 (Biological)
Treatment Arm 3 (Stage 1A)
干预措施: PF-04856883 (Biological)
Treatment Arm 4 (Stage 1A)
干预措施: PF-04856883 (Biological)
Treatment Arm 6 (Stage 1B)
干预措施: PF-04856883 (Biological)
Treatment Arm 13 (Stage 2)
干预措施: PF-04856883 (Biological)
Treatment Arm 8 (Stage 1B)
干预措施: PF-04856883 (Biological)
结局指标
主要结局
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiograms (ECG)
时间窗: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
ECG parameters included pulse rate (PR) interval, QRS interval, corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). ECG criteria of clinically significant concern were 1) PR interval: greater than equal to (\>=) 25 percent (%) increase when baseline greater than (\>)200 milliseconds (msec); or increase \>=50% when baseline less than or equal to (\<=200) msec; 2) QRS interval: \>=25% increase when baseline \>100 msec; \>=50% increase when baseline \<= 100 msec; 3) QTCF interval: QTc interval using Fridericia's formula (QTcF interval) and Bazett's formula (QTcB interval): absolute value 450 - \<480 msec, 480 - \<500 msec \>=500; absolute change 30 - \<60, \>=60 msec. The number of participants with potentially clinically significant ECG findings at any visit were reported. IFB = increase from baseline.
Number of Participants With Clinically Significant Physical Examination Findings
时间窗: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
Physical examination included examination of general appearance, head, ears, eyes (including fundoscopy), nose, mouth, throat, neck (including thyroid), skin, breast (optional), cardiac, respiratory, gastrointestinal, musculoskeletal and neurological systems.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
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 28 days after last dose (Day 50) that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Clinically Significant Abnormalities in Laboratory Measurements
时间窗: Stage 1: Baseline up to Day 29; Stage 2: Baseline up to Day 50
Following parameters were analyzed for laboratory examination: Hematology: hemoglobin, hematocrit, red blood cell (RBC) \<0.8\*lower limit of the reference range (LLRR); leukocytes \<0.6\*LLRR or \>1.5\*ULRR; platelet count \<0.5\*LLRR or \>1.75\*upper limit of the reference range (ULRR); total neutrophils (absolute \[abs\]), lymphocytes (abs) \<0.8\*LLRR or \>1.2\*ULRR; eosinophils (abs), basophils (abs), monocytes (abs) \>1.2\*ULRR; chemistry (total bilirubin, direct bilirubin, indirect bilirubin \>1.5\*ULRR; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase \>3\*ULRR, albumin, total protein \<0.8\*LLRR or \>1.2\*ULRR; blood urea nitrogen (BUN), creatinine \>1.3\*ULRR; glucose (fasting) \<0.6\*LLRR or \>1.5\*ULRR; uric acid \>1.2\* ULRR; sodium \<0.95\*LLRR or \>1.05\*ULRR; potassium, chloride, bicarbonate, calcium \<0.9\*LLRR or \>1.1\*ULRR. Urinalysis: Urine white blood cell (WBC), Urine RBC =\>20/ high-power field (HPF).
Number of Participants With Vital Sign Abnormalities
时间窗: Stage 1: Baseline up to Day 29; Stage 2 : Baseline up to Day 50
Criteria for vital signs abnormalities: sitting/supine systolic pulse rate less than (\<) 40 beats per minute (bpm) or greater than (\>) 120 bpm, standing/supine systolic pulse \< 40 bpm or \> 140 bpm, systolic blood pressure of \>=30 millimeters of mercury (mmHg) change from baseline and systolic blood pressure \<90 mmHg, diastolic blood pressure \>=20 mmHg change from baseline and diastolic blood pressure \<50 mm Hg.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 2(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) of PF-04856883: Stage 1(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1)
- Terminal Elimination Half- Life (t1/2) of PF-04856883: Stage 1(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1)
- Change From Baseline in Post-prandial Glucose Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2(Baseline, Day 3, 15, 24, 29 and 50)
- Maximum Observed Plasma Concentration (Cmax) of PF-04856883: Stage 1(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 1(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1)
- Area Under the Concentration Time Curve From Time Zero to Time Tau (AUCtau) of PF-04856883: Stage 2(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168 hours postdose Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168 hours postdose Day 22)
- Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 1(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1)
- Change From Baseline in Post-prandial Glucose Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1(Baseline, Day 3 and 8)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04856883: Stage 2(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336 hours postdose on Day 1; predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22)
- Apparent Clearance (CL/F) of PF-04856883: Stage 2(predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22)
- Apparent Volume of Distribution (Vz/F) of PF-04856883: Stage 2(predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 15, 22 and 29: Stage 1(Baseline, Day 2, 4, 6, 15, 22 and 29)
- Change From Baseline in 24 Hours Glucose Normalized Area Under the Curve (NAUC) Profile at Day 30: Stage 2(Baseline, Day 30)
- Apparent Clearance (CL/F) of PF-04856883: Stage 1(predose (0 hour), 1, 6, 12, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 1)
- Terminal Elimination Half-life (t1/2) of PF-04856883: Stage 2(predose (0 hour), 1, 2, 6, 24, 48, 72, 120, 168, 336, 504, 672 hours postdose on Day 22)
- Change From Baseline in Insulin Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2(Baseline, Day 3, 15, 24, 29 and 50)
- Change From Baseline in C-Peptide Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1(Baseline, Day 3 and 8)
- Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Day 29 and 50: Stage 2(Baseline, Day 29 and 50)
- Change From Baseline in Insulin Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3 and 8: Stage 1(Baseline, Day 3 and 8)
- Change From Baseline in C-Peptide Area Under the Curve (AUC) After Mixed Meal Tolerance Test (MMTT) at Day 3, 15, 24, 29 and 50: Stage 2(Baseline, Day 3, 15, 24, 29 and 50)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43: Stage 2(Baseline, Day 2, 4, 6, 8, 22, 23, 25, 27, 30, 36 and 43)
- Change From Baseline in Fructosamine Levels at Day 8, 15 and 29: Stage 1(Baseline, Day 8, 15 and 29)
- Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15, 22, 29 and 50: Stage 2(Baseline, Day 8, 15, 22, 29 and 50)
- Number of Participants With Anti-Drug Antibodies (ADA): Stage 1(Day 1 and 29)
- Change From Baseline in Fructosamine Levels at Day 8, 15, 22, 29 and 50: Stage 2(Baseline, Day 8, 15, 22, 29 and 50)
- Change From Baseline in 1, 5 Anhydroglucitol at Day 8, 15 and 29: Stage 1(Baseline, Day 8, 15 and 29)
- Number of Participant With Anti-Drug Antibodies (ADA): Stage 2(Day 1, 29 and 50)