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

NCT05788328 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: C3991047
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Dabigatran etexitlate; Rosuvastatin; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; BCRP substrate; P-gp substrate; Anticoagulant; Antihyperlipidemic

Outcome Measures

Primary Outcomes (4)

• Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in 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.

  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

• Area Under the Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUClast) of Total Dabigatran in Period 1, 4 and 7

  AUClast was determined using the linear/log trapezoidal method.

  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 of Rosuvastatin in 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.

  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 of Rosuvastatin in Period 2, 5 and 8

  AUClast was determined using the linear/log trapezoidal method.

  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 (20)

• 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)

Study Arms (8)

Period 1

ACTIVE COMPARATOR

Participants will receive dabagatrin etexilate (DE) as a single dose

Drug: Dabigatran etexilate (DE)

Period 2

ACTIVE COMPARATOR

Participants will receive rosuvastatin as a single dose

Drug: Rosuvastatin

Period 3

ACTIVE COMPARATOR

Participants will receive PF-07081532 daily titrated

Drug: PF-07081532

Period 4

EXPERIMENTAL

Participants will receive PF-07081532 daily and DE as a single dose

Drug: Dabigatran etexilate (DE); Drug: PF-07081532

Period 5

EXPERIMENTAL

Participants will receive PF-07081532 daily and rosuvastatin as a single dose

Drug: Rosuvastatin; Drug: PF-07081532

Period 6

ACTIVE COMPARATOR

Participants will receive PF-07081532 daily titrated

Drug: PF-07081532

Period 7

EXPERIMENTAL

Participants will receive PF-07081532 daily and DE as a single dose

Drug: Dabigatran etexilate (DE); Drug: PF-07081532

Period 8

EXPERIMENTAL

Participants will receive PF-07081532 daily and rosuvastatin as a single dose

Drug: Rosuvastatin; Drug: PF-07081532

Interventions

Dabigatran etexilate (DE) DRUG

Dabigatran etexilate (DE) as oral capsule

Also known as: Pradaxa

Period 1; Period 4; Period 7

Rosuvastatin DRUG

Rosuvastatin as oral tablet

Also known as: Crestor

Period 2; Period 5; Period 8

PF-07081532 DRUG

PF-07081532 as oral tablets

Also known as: Lotiglipron

Period 3; Period 4; Period 5; Period 6; Period 7; Period 8

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Qps-Mra, Llc

South Miami, Florida, 33143, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Dabigatran; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2023
• First Posted: March 28, 2023
• Study Start: March 27, 2023
• Primary Completion: September 11, 2023
• Study Completion: September 11, 2023
• Last Updated: November 15, 2024
• Results First Posted: November 15, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)