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

Sponsor

Pfizer (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05788328

Collaborator

(none)

Enrollment

Arms

6.1

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Dabigatran etexilate (DE) Drug: Rosuvastatin Drug: PF-07081532	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Masking Description:

Open label

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Mar 21, 2023

Anticipated Primary Completion Date :

Sep 23, 2023

Anticipated Study Completion Date :

Sep 23, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Period 1 Participants will receive dabagatrin etexilate (DE) as a single dose	Drug: Dabigatran etexilate (DE) Dabigatran etexilate (DE) as oral capsule Other Names: Pradaxa
Active Comparator: Period 2 Participants will receive rosuvastatin as a single dose	Drug: Rosuvastatin Rosuvastatin as oral tablet Other Names: Crestor
Active Comparator: Period 3 Participants will receive PF-07081532 daily titrated	Drug: PF-07081532 PF-07081532 as oral tablets Other Names: Lotiglipron
Experimental: Period 4 Participants will receive PF-07081532 daily and DE as a single dose	Drug: Dabigatran etexilate (DE) Dabigatran etexilate (DE) as oral capsule Other Names: Pradaxa Drug: PF-07081532 PF-07081532 as oral tablets Other Names: Lotiglipron
Experimental: Period 5 Participants will receive PF-07081532 daily and rosuvastatin as a single dose	Drug: Rosuvastatin Rosuvastatin as oral tablet Other Names: Crestor Drug: PF-07081532 PF-07081532 as oral tablets Other Names: Lotiglipron
Active Comparator: Period 6 Participants will receive PF-07081532 daily titrated	Drug: PF-07081532 PF-07081532 as oral tablets Other Names: Lotiglipron
Experimental: Period 7 Participants will receive PF-07081532 daily and DE as a single dose	Drug: Dabigatran etexilate (DE) Dabigatran etexilate (DE) as oral capsule Other Names: Pradaxa Drug: PF-07081532 PF-07081532 as oral tablets Other Names: Lotiglipron
Experimental: Period 8 Participants will receive PF-07081532 daily and rosuvastatin as a single dose	Drug: Rosuvastatin Rosuvastatin as oral tablet Other Names: Crestor Drug: PF-07081532 PF-07081532 as oral tablets Other Names: Lotiglipron

Outcome Measures

Primary Outcome Measures

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of total dabigatran [if data permits otherwise Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)] [0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7]
To estimate the effect of multiple dose PF-07081532 on the single-dose of dabigatran etexilate (DE) in otherwise healthy overweight or obese participants.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of rosuvastatin [if data permits otherwise Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)] [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8]
To estimate the effect of multiple dose PF-07081532 on the single-dose of rosuvastatin in otherwise healthy overweight or obese participants.

Secondary Outcome Measures

Percentage of participants reporting Treatment Emergent Adverse Events (TEAE) [up to 28-35 days post dose]
Percentage of participants reporting clinical laboratory abnormalities [up to Day 53 (up to 7-10 days post last dose if available)]
including vital signs, body weight, and ECG parameters.
Number of Participants responding yes to any suicidal behavior question according to Columbia-Suicide Severity Rating Scale (C-SSRS) [Day -1, Day 14, Day 28, Day 42, Day 53 (at follow up 7-10 days post last dose if available)]
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. Participants who respond "yes" to any suicidal behavioral question on the C-SSRS will not be permitted in the study.
Number of participants with a score of ≥15 on Patient Health Questionnaire-9 (PHQ-9) [Day -1, Day 14, Day 28, Day 42, Day 53 (at follow up 7-10 days post last dose if available)]
PHQ9-9 is a 9 item self-report scale for the assessment of depressive symptoms. A PHQ-9 score of ≥15 indicates clinically significant depression and serves as an exclusion criterion for this study.
Maximum Observed Plasma Concentration (Cmax) of total dabigatran [0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of total dabigatran [0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7]
Apparent Oral Clearance (CL/F) of total dabigatran [0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7]
As data permits
Apparent Volume of Distribution (Vz/F) of total dabigatran [0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7]
As data permits
Plasma Decay Half-Life (t1/2) of total dabigatran [0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7]
As data permits
Maximum Observed Plasma Concentration (Cmax) of rosuvastatin [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of rosuvastatin [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8]
Apparent Oral Clearance (CL/F) of rosuvastatin [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8]
As data permits
Apparent Volume of Distribution (Vz/F) of rosuvastatin [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8]
As data permits
Plasma Decay Half-Life (t1/2) of rosuvastatin [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8]
As data permits
Area under the plasma concentration time-curve from zero to time 24 hours (AUC24) of PF-07081532 [0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Periods 4 and 7]
Maximum Observed Plasma Concentration (Cmax) of PF-07081532 [0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Periods 4 and 7]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07081532 [0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Periods 4 and 7]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

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