A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP STUDY TO EVALUATE THE PHARMACOKINETICS OF PF-07081532 IN ADULT PARTICIPANTS WITH TYPE 2 DIABETES MELLITUS WITH VARYING DEGREES OF RENAL IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT RENAL IMPAIRMENT
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Maximum Observed Concentration (Cmax) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
研究概览
简要总结
The purpose of this study is to understand the effects of kidney functional impairment may have on the study medicine (PF-07081532). People with certain level of kidney functional impairment may process PF-07081532 differently from healthy people. PF-07081532 is developed as a potential treatment for type II diabetes.
Participants will take the study medicine as a tablet by mouth once at the study clinic and then will stay at the study clinic for about 7 days. During that time, the study team will monitor their treatment experience and take some blood samples to test the level of PF-07081532. This will help us understand if certain degree of kidney functional impairment will have an effect on the study medicine PF-07081532.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Stable renal function (for participants not on dialysis) defined as ≤25% difference between 2 measurements of BSA-unnormalized eGFR
- •A prior diagnosis of T2DM with an HbA1c ≥6% and ≤10.5%
- •Women may be of child-bearing potential
- •BMI of 17.5 to 45.4 kg/m2
- •NORMAL FUNCTION (GROUP 1): Normal renal function (mean eGFR ≥90 mL/min) based on an average of measures from Screening visits S1 and S2 (eGFR should be calculated using the 2021 CKD EPI Scr-Scys combined equation:
- •Demographically comparable to participants with impaired renal function at Screening
- •A body weight within ±15 kg of the mean body weight of the pooled renal impairment groups (Groups 2, 3 and 4)
- •An age within ±10 years of the mean age of the pooled renal impairment groups (Groups 2, 3 and 4)
- •Attempts will be made to ensure that the male to female distribution in Group 1 is comparable to that in the pooled renal impairment groups (Groups 2, 3 and 4).
排除标准
- •Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes, or history of diabetic ketoacidosis.
- •History of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II-IV heart failure, or transient ischemic attack within 3 months of Screening
- •Personal or family history of MTC or MEN2, or participants with suspected MTC per the investigator's judgement.
- •History of acute pancreatitis within 6 months before Screening or any history of chronic pancreatitis.
- •Urinary incontinence.
- •Participants with acute renal disease.
- •Renal allograft recipients.
- •Participants who have previously received a kidney, liver, or heart transplant.
研究组 & 干预措施
Group 1
Participants without renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
干预措施: PF-07081532 (Drug)
Group 2
Participants with mild renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
干预措施: PF-07081532 (Drug)
Group 3
Participants with moderate renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
干预措施: PF-07081532 (Drug)
Group 4
Participants with severe renal impairment will receive a single 20 mg dose of PF 07081532, administered orally
干预措施: PF-07081532 (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Plasma Cmax was observed directly from data.
Unbound Cmax (Cmax,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
Cmax,u was calculated as fu\*Cmax. Plasma Cmax was observed directly from data. fu was defined as the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
AUCinf was calculated as AUClast + (Clast\*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast\* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Unbound AUCinf (AUCinf,u) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
AUCinf,u was calculated as fu\*AUCinf. AUCinf was calculated as AUClast + (Clast\*/kel). AUClast was defined as area under the plasma concentration-time profile from time 0 to the time last measurable concentration, and was calculated using linear/log trapezoidal method. Clast\* was defined as the predicted plasma concentration at the last quantifiable time point estimated from log-linear regression analysis. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. fu was the fraction of unbound drug in plasma, and was obtained from measurement of protein binding.
Unbound Fraction (fu) for PF-07081532 Following a Single Oral Dose of PF-07081532 20 mg in Participants With Varying Degrees of Renal Impairment
时间窗: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 15, 24, 36, 48, 72, 96, 120, 144 hours post dose on Day 1
fu was the ratio of unbound drug concentration to the total drug concentration, and was obtained from measurement of protein binding.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From time of administration of study treatment on Day 1 up to the end of the study (up to a maximum of 31 days post dose))
- Number of Participants With Vital Signs Data Meeting Pre-Defined Categorical Criteria(At admission on Day -1, pre-dose, and 24, 72, and 144 hours post the dose on Day 1)
- Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Defined Categorical Criteria(Pre-dose, and 144 hours post the dose on Day 1)
- Number of Participants With Laboratory Test Abnormalities(Pre-dose, 72 and 144 hours post dose on Day 1)