A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO ESTIMATE THE EFFECT OF PF-07081532 ADMINISTRATION ON THE SINGLE-DOSE PHARMACOKINETICS OF DABIGATRAN AND ROSUVASTATIN IN OVERWEIGHT OR OBESE ADULT PARTICIPANTS
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in Period 1, 4 and 7
研究概览
简要总结
The purpose of the study was to understand the effect of PF-07081532 on the movement of Dabigatran and Rosuvastatin into, though, and out of the body in healthy overweight or obese adult participants. This study also aims to collect data on safety and how tolerable the study medicine is.
The study is seeking for participants who are:
- Male or female who are 18 years of age or older.
- Healthy but are overweight or obese. Participants will receive dabigatran and rosuvastatin as single doses by mouth 3 times during the study. The amount of the study medicine PF-07081532 will be adjusted over time until any interactions are seen.
PF-07081532 is taken daily by mouth in 8 Study Periods while admitted into the study clinic over 53 days. Once discharged from the study clinic, participants will have a follow-up visit 7 to 10 days post last dose of study medicine. Then another follow-up via telephone contact, 28 to 35 days post last dose of study medicine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Otherwise healthy female and male participants must be at least 18 years of age at the time of signing the ICD (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, physical examination, including blood pressure and pulse rate measurement, standard 12-lead ECG and clinical laboratory tests)
- •BMI: ≥25.0 kg/m2 at Screening
- •Stable body weight, defined as <5 kg change (per participant report) for 90 days before Screening
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease
- •Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at Screening
- •History of myocardial infarction, unstable angina, arterial revascularization, mechanical prosthetic heart valve, stroke, New York Association Functional Class II-IV heart failure, or transient ischemic attack within 6 months of Screening
- •Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin)
- •Personal or family history of MTC or MEN2, or study participants with suspected MTC per the investigator's judgment
- •Acute pancreatitis, a history of repeated episodes of acute pancreatitis, or history of chronic pancreatitis
- •Symptomatic gallbladder disease
- •Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders
- •History of depressive disorder or history of other severe psychiatric disorders within the last 2 years from Screening
- •Any lifetime history of a suicide attempt
- •Known medical history of active liver disease, or prior known drug-induced liver injury
- •History of HIV infection
- •Recent history of bleeding, or risks of bleeding, or abnormal coagulation test (INR >1.3) result at Screening
- •Use of prohibited medications
- •Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest
- •Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study result
- •Participants with clinical laboratory test abnormalities at Screening
研究组 & 干预措施
Period 1
Participants will receive dabagatrin etexilate (DE) as a single dose
干预措施: Dabigatran etexilate (DE) (Drug)
Period 2
Participants will receive rosuvastatin as a single dose
干预措施: Rosuvastatin (Drug)
Period 3
Participants will receive PF-07081532 daily titrated
干预措施: PF-07081532 (Drug)
Period 4
Participants will receive PF-07081532 daily and DE as a single dose
干预措施: Dabigatran etexilate (DE) (Drug)
Period 4
Participants will receive PF-07081532 daily and DE as a single dose
干预措施: PF-07081532 (Drug)
Period 5
Participants will receive PF-07081532 daily and rosuvastatin as a single dose
干预措施: Rosuvastatin (Drug)
Period 5
Participants will receive PF-07081532 daily and rosuvastatin as a single dose
干预措施: PF-07081532 (Drug)
Period 6
Participants will receive PF-07081532 daily titrated
干预措施: PF-07081532 (Drug)
Period 7
Participants will receive PF-07081532 daily and DE as a single dose
干预措施: Dabigatran etexilate (DE) (Drug)
Period 7
Participants will receive PF-07081532 daily and DE as a single dose
干预措施: PF-07081532 (Drug)
Period 8
Participants will receive PF-07081532 daily and rosuvastatin as a single dose
干预措施: Rosuvastatin (Drug)
Period 8
Participants will receive PF-07081532 daily and rosuvastatin as a single dose
干预措施: PF-07081532 (Drug)
结局指标
主要结局
Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in Period 1, 4 and 7
时间窗: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Area Under the Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUClast) of Total Dabigatran in Period 1, 4 and 7
时间窗: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
AUClast was determined using the linear/log trapezoidal method.
AUCinf of Rosuvastatin in Period 2, 5 and 8
时间窗: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
AUClast of Rosuvastatin in Period 2, 5 and 8
时间窗: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
AUClast was determined using the linear/log trapezoidal method.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)- All Causalities(From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days))
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)(During treatment of the study (maximum up to 48 days))
- Number of Participants With Clinically Significant Vital Signs(From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days))
- Percent Change From Baseline in Body Weight(Baseline, Day 1 and 8 of Period 3, Day 1 of Period 5, Day 5 and 12 of Period 6, Day 1 and 5 of Period 8 and follow-up (28-35 days post last dose; up to 76 to 83 days))
- Number of Participants With Pre-defined Criteria of Electrocardiogram (ECG) Parameters(From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days))
- Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS)(From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days))
- Number of Participants According to Patient Health Questionnaire-9 (PHQ-9) Classification(Day 1 prior to treatment (Day -1) in Period 1; Day 8 of Period 3; Days 5 of Period 6; Day 1 and 5 of Period 8; Follow-up: up to 53 to 56 days post last dose of study intervention)
- Maximum Observed Concentration (Cmax) of Total Dabigatran in Period 1, 4 and 7(Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7)
- Time for Cmax (Tmax) of Total Dabigatran in Period 1, 4 and 7(Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7)
- Terminal Half-Life (t1/2) of Total Dabigatran in Period 1, 4 and 7(Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7)
- Apparent Volume of Distribution (Vz/F) of Total Dabigatran in Period 1, 4 and 7(Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7)
- Apparent Oral Clearance (CL/F) of Total Dabigatran in Period 1, 4 and 7(Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7)
- Cmax of Rosuvastatin in Period 2, 5 and 8(Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8)
- Tmax of Rosuvastatin in Period 2, 5 and 8(Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8)
- t1/2 of Rosuvastatin in Period 2, 5 and 8(Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8)
- Vz/F of Rosuvastatin in Period 2, 5 and 8(Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8)
- CL/F of Rosuvastatin in Period 2, 5 and 8(Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8)
- Area Under the Concentration-Time Curve From Time 0 to Time 24 Hours (AUC24) of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively(Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8)
- Cmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively(Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8)
- Tmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively(Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8)