Clinical trial NCT05788328: A Drug-Drug Interaction Study to Estimate the Effect of PF-07081532 on the Pharmacokinetics of Dabigatran and Rosuvastatin in Overweight or Obese Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Keywords: Dabigatran etexitlate
Rosuvastatin
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
BCRP substrate
P-gp substrate
Anticoagulant
Antihyperlipidemic
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-03-28
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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)
2. BMI: ≥25.0 kg/m2 at Screening
3. Stable body weight, defined as \<5 kg change (per participant report) for 90 days before Screening

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease
2. Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at Screening
3. 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
4. Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin)
5. Personal or family history of MTC or MEN2, or study participants with suspected MTC per the investigator's judgment
6. Acute pancreatitis, a history of repeated episodes of acute pancreatitis, or history of chronic pancreatitis
7. Symptomatic gallbladder disease
8. Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders
9. History of depressive disorder or history of other severe psychiatric disorders within the last 2 years from Screening
10. Any lifetime history of a suicide attempt
11. Known medical history of active liver disease, or prior known drug-induced liver injury
12. History of HIV infection
13. Recent history of bleeding, or risks of bleeding, or abnormal coagulation test (INR \>1.3) result at Screening
14. Use of prohibited medications
15. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest
16. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study result
17. Participants with clinical laboratory test abnormalities at Screening

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in Period 1, 4 and 7
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUClast) of Total Dabigatran in Period 1, 4 and 7
timeFrame: 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
measure: AUCinf of Rosuvastatin in Period 2, 5 and 8
timeFrame: 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
measure: AUClast of Rosuvastatin in Period 2, 5 and 8
timeFrame: 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
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)- All Causalities
timeFrame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: During treatment of the study (maximum up to 48 days)
measure: Number of Participants With Clinically Significant Vital Signs
timeFrame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
measure: Percent Change From Baseline in Body Weight
timeFrame: 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)
measure: Number of Participants With Pre-defined Criteria of Electrocardiogram (ECG) Parameters
timeFrame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
measure: Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
measure: Number of Participants According to Patient Health Questionnaire-9 (PHQ-9) Classification
timeFrame: 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
measure: Maximum Observed Concentration (Cmax) of Total Dabigatran in Period 1, 4 and 7
timeFrame: 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
measure: Time for Cmax (Tmax) of Total Dabigatran in Period 1, 4 and 7
timeFrame: 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
measure: Terminal Half-Life (t1/2) of Total Dabigatran in Period 1, 4 and 7
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of Total Dabigatran in Period 1, 4 and 7
timeFrame: 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
measure: Apparent Oral Clearance (CL/F) of Total Dabigatran in Period 1, 4 and 7
timeFrame: 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
measure: Cmax of Rosuvastatin in Period 2, 5 and 8
timeFrame: 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
measure: Tmax of Rosuvastatin in Period 2, 5 and 8
timeFrame: 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
measure: t1/2 of Rosuvastatin in Period 2, 5 and 8
timeFrame: 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
measure: Vz/F of Rosuvastatin in Period 2, 5 and 8
timeFrame: 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
measure: CL/F of Rosuvastatin in Period 2, 5 and 8
timeFrame: 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
measure: 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
timeFrame: 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
measure: Cmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
timeFrame: 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
measure: Tmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
timeFrame: 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
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Qps-Mra, Llc
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: