NCT04909853已完成1 期
A PHASE 1, NON-RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-07321332 BOOSTED WITH RITONAVIR IN ADULT PARTICIPANTS WITH RENAL IMPAIRMENT AND IN HEALTHY PARTICIPANTS WITH NORMAL RENAL FUNCTION.
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 35
- 试验地点
- 5
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of PF-07321332
研究概览
简要总结
This is a Phase 1, non-randomized, open-label, 2-part study to investigate the effect of renal impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of PF-07321332 in combination with the PK boosting agent ritonavir. Participants will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: will be conducted in approximately 24 participants (approximately 8 per group) with stable mild or moderate renal impairment and a control group of participants with normal renal function. Part 2 will be conducted in approximately 8 participants with stable severe renal impairment.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female, non-smoker and/or light smoker
- •Have a diagnosis of stable renal impairment
- •Meet the following estimated glomerular filtration rate (eGFR) criteria during the screening period (based on 2 Screening visits) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation:
- •Mild renal impairment: eGFR between 60 - 89 mL/min.
- •Moderate renal impairment: eGFR ≥30 mL/min and <60 mL/min.
- •Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis.
- •Normal renal function: eGFR ≥90 mL/min
- •Renal impairment participants:
- •Any form of renal impairment except acute nephritic syndrome (participants with history of previous nephritic syndrome but in remission can be included).
- •Good general health commensurate with the population with chronic kidney disease (renal impairment).
- •Stable concomitant drug regimen for the management of individual participant's medical conditions, so long as they are considered necessary for the welfare of the study participants (eg, standard therapy for underlying diseases), and are not contraindicated with study drug, and are unlikely to interfere with the PK of study drug.
- •Healthy participants with normal renal function:
- •No clinically relevant abnormalities identified by a detailed medical history, full physical examination, including temperature, blood pressure (BP) and pulse rate measurement, 12 lead ECG and clinical laboratory tests.
- •Demographically comparable to the group of participants with impaired renal function.
- •Each participant's body weight within ±15 kg of the mean body weight of renal impairment group.
- •Each participant's age within ±10 years of the mean age of the renal impairment group.
排除标准
- •Positive test result for SARS-CoV-2 infection at the time of screening or Day -
- •History of HIV infection, hepatitis B, or hepatitis C; positive testing at screening for HIV, HBsAg, HBcAb, or HCVAb. As an exception a positive HBsAb test due to Hepatitis B vaccination is allowed.
- •Renal transplant recipients.
- •Urinary incontinence without catheterization
- •Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, cholecystectomy, appendectomy).
- •Participants who have been vaccinated with COVID-19 vaccines within the past 2 weeks of dosing, or are to be vaccinated with these vaccines at any time during the study.
- •A positive urine drug test, for illicit drugs, at Screening
- •aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >2 × upper limit of normal (ULN)
- •Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is≤ ULN.
- •History of sensitivity reactions to ritonavir or any of the formulation components of PF 07321332 or ritonavir.
- •Female participants of childbearing potential who are unwilling or unable to use highly effective methods of contraception as outlined in Section 5.3.4 for the duration of the study and for at least 28 days after the administration of investigational product, pregnant female participants, female participants planning to become pregnant during the duration of the study until 28 days after the administration of investigational product, breastfeeding female participants.
- •Renal impairment participants:
- •Participants requiring hemodialysis and/or peritoneal dialysis
- •Participants with other clinically significant disease that may affect the safety of the participant or that may affect the PK of PF-
- •Participants with any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephrotic.
- •Healthy participants with normal renal function:
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •Screening supine BP >140 mm Hg (systolic) or >90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is >140 mm Hg (systolic) or >90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
研究组 & 干预措施
PF-07321332
Experimental
PF 07321332/ritonavir
干预措施: PF-07321332/ritonavir (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of PF-07321332
时间窗: Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1
Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332
时间窗: Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1
AUCinf was calculated by AUClast + (Clast/kel). AUClast was the area under the plasma concentration-time profile from time 0 to the time of Clast. Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48)
时间窗: Part 1 and Part 2: 0 to 48 hours post dose on Day 1
Total amount of unchanged drug excreted in the urine over 48 hours.
Renal Clearance (CLr) of PF-07321332
时间窗: Part 1 and Part 2: 0 to 48 hours post dose on Day 1
Renal clearance was calculated as total amount of unchanged drug excreted in the urine over 48 hours (Ae48) divided by area under the plasma concentration-time profile from time 0 to 48 hours post dose.
次要结局
- Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12)(Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 1)
- Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities(Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs(Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days))
- Number of Participants With Clinical Laboratory Abnormalities(Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days))
- Number of Participants With Clinically Significant Vital Signs Abnormalities(Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days))
- Number of Participants With Clinically Significant Findings in Physical Examination(Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days))
- Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24)(Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose on Day 1)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332(Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1)
- Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332(Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1)
- Apparent Clearance (CL/F) of PF-07321332 From Plasma(Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1)
- Apparent Volume of Distribution (Vz/F) of PF-07321332(Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1)
- Terminal Elimination Plasma Half-life (t1/2) of PF-07321332(Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1)
研究者
研究点 (5)
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