A PHASE 1, OPEN-LABEL, SINGLE-DOSE, PARALLEL-COHORT STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF PF-07328948 IN ADULTS WITH AND WITHOUT VARYING DEGREES OF HEPATIC IMPAIRMENT
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 26
- 试验地点
- 3
- 主要终点
- Fraction of Unbound Drug in Plasma (Fu) of PF-07328948
研究概览
简要总结
The purpose of this study is to understand the effects of decreased liver function on the study medicine (PF-07328948). People with decreased liver function may process the study medicine differently from healthy people.
Study is seeking participants who:
- Are between 18 and 75 years of age.
- Have a BMI (body mass index) of 17.5 to 40 kg/m2, inclusive, and a total body weight of more than or equal to 45 kilograms or 99 pounds.
Participants will take the study medicine as a tablet once at the study clinic and then will stay onsite for about 6 days.
During this time, the study team will check for the participant's treatment experience and take some blood samples to test the level of PF-07328948. This will help understand if certain level of decreased liver function could affect the study medicine being processed in the body.
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 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female of nonchildbearing potential, between the ages of 18 (inclusive) and 75 years, at the screening visit.
- •Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •BMI of 17.5 to 40.0 kg/m2 (inclusive), and a total body weight ≥45 kg (99 lb).
- •Group 4 only: at screening, no clinically relevant abnormalities identified by a detailed medical history, physical exam, including blood pressure and pulse rate measurement, ECG and clinical laboratory tests.
- •Group 4 only: no known or suspected hepatic impairment and meet the criteria based on screening laboratory liver function tests.
- •Groups 1, 2 & 3 only: stable hepatic impairment that meets criteria for Class A, B, or C of the Child-Pugh classification with no clinically significant change in disease status within 28 days before screening.
- •Groups 1, 2 & 3 only: stable concomitant medications for the management of individual participant's medical history.
排除标准
- •Any condition possibly affecting drug absorption
- •At screening, a positive result for HIV antibodies.
- •Evidence of a prothrombotic state, including history of deep vein thrombosis, pulmonary embolism, or arterial thrombosis, or known genetic predisposition.
- •Other medical or psychiatric condition or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study.
- •Use of specific prohibited prior/concomitant therapies
- •Use of an investigational product within 30 days or 5 half-lives (whichever longer).
- •eGFR<60 mL/min/1.73m2 at screening.
- •A positive urine drug test at screening or admission to study clinic.
- •At screening or admission to study clinic, a positive breath alcohol test.
- •History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of screening.
- •Group 4 only: evidence of chronic liver disease including history of hepatitis, hepatitis B, or hepatitis C.
- •Group 4 only: screening ECG demonstrating QTcF interval >450 ms or a QRS interval >120 ms.
- •Group 4 only: screening seated systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg
- •Group 1, 2 & 3 only: Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy (defined as <1 year in Groups 2 & 3 and <6 months for Group 1 only).
- •Group 1, 2 & 3 only: a diagnosis of hepatic dysfunction secondary to any acute ongoing hepatocellular process that is documented by medical history, physical exam, liver biopsy, hepatic ultrasound, CT scan, or MRI.
- •Group 1, 2 & 3 only: history of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than 4 weeks prior to screening.
- •Group 1, 2 & 3 only: signs of clinically active Grade 3 or 4 hepatic encephalopathy
- •Groups 1, 2 & 3 only: severe ascites and/or pleural effusion, except for those categorized in Group 4 who may be enrolled provided participant is medically stable, per the study doctor's judgment.
- •Groups 1, 2 & 3 only: previously received a kidney, liver, or heart transplant.
- •Groups 1, 2, & 3 only: screening ECG demonstrating a QTcF interval >470 ms or a QRS interval >120 ms.
- •Groups 1, 2 & 3 only: persistent severe, uncontrolled hypertension at screening, admission to study clinic, or pre-dose on Day
- •Groups 1, 2 & 3 only: ALT or AST >5x upper limit of normal on clinical laboratory tests at screening.
研究组 & 干预措施
Group 2: PF-07328948 participants with moderate hepatic impairment
Participants with moderate hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.
干预措施: PF-07328948 (Drug)
Group 1: PF-07328948 participants with severe hepatic impairment
Participants with severe hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.
干预措施: PF-07328948 (Drug)
Group 3: PF-07328948 participants with mild hepatic impairment
Participants with mild hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.
干预措施: PF-07328948 (Drug)
Group 4: PF-07328948 participants without hepatic impairment
Participants without hepatic impairment will receive a single dose of PF-07328948, administered orally as 1 PF-07328948 tablet.
干预措施: PF-07328948 (Drug)
结局指标
主要结局
Fraction of Unbound Drug in Plasma (Fu) of PF-07328948
时间窗: At 0 (prior to dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post dose on Day 1
Fu is the fraction of unbound drug in plasma, which is calculated by Cu/C (where Cu represents unbound concentration and C represents total concentration).
Unbound AUCinf (AUCinf,u) of PF-07328948
时间窗: At 0 (prior to dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post dose on Day 1
AUCinf is the area under the plasma concentration-time profile from time zero extrapolated to infinite time. AUCinf,u is the unbound AUCinf.
Unbound Cmax (Cmax,u) of PF-07328948
时间窗: At 0 (prior to dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 168 hours post dose on Day 1
Cmax is the maximum plasma concentration. Cmax,u is the unbound Cmax.
次要结局
- Number of Participants with Treatment Emergent Adverse Events (TEAEs)(Day 1 to Day 36)