A Study to Understand the Effect of a Study Medicine Called ARV-471 on Dabigatran Etexilate in Healthy Adults

NCT05673889 | Completed Phase 1 Results

• 2 other identifiers: C48910082022-003397-23
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to understand if ARV-471 affects how a medicine called, dabigatran etexilate, gets absorbed or processed into the body in healthy adults. All participants in this study will receive one dose of dabigatran etexilate alone by mouth in Period 1. In Period 2, everyone will receive one dose of dabigatran etexilate by mouth approximately 90 minutes after receiving one dose of ARV-471 by mouth. The levels of dabigatran in Period 1 will be compared to the levels of dabigatran in Period 2. This will help us to determine if and how ARV-471 affects dabigatran gets absorbed into the body differently in healthy adults. All participants will stay at the study clinic for approximately 8 days and 7 nights.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran When Dabigatran Etexilate is Administered Alone Versus When Dabigatran Etexilate is Administered With ARV-471

  Cmax was defined as maximum observed plasma concentration. Cmax for total dabigatran was observed directly from data.

  Period 1 and 2: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on Day 1

• Area Under the Plasma Concentration-time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Total Dabigatran When Dabigatran Etexilate is Administered Alone vs Dabigatran Etexilate is Administered With ARV-471

  AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. AUCinf was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.

  Period 1 and 2: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose on Day 1

Secondary Outcomes (4)

• Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)

  From the first dose (Day 1) up to 35 days after the last dose (Day 5) of study intervention (up to 40 days)

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

  Baseline (Period 1 Day -1) up to Period 2 Day 3 (8 days)

• Number of Participants With Clinically Significant Vital Signs

  Baseline (Period 1 Day 1) up to Period 2 Day 3 (7 days)

• Number of Participants With Electrocardiogram (ECG) Abnormalities

  Baseline (Period 1 Day 1) up to Period 2 Day 3 (7 days)

Study Arms (1)

Dabigatran etexilate with and without ARV-471

EXPERIMENTAL

Dabigatran etexilate administered as a single dose in Period 1 and Period 2. ARV-471 administered as a single dose in Period 2.

Drug: ARV-471; Drug: Dabigatran etexilate

Interventions

ARV-471 DRUG

Experimental

Also known as: PF-07850327

Dabigatran etexilate with and without ARV-471

Dabigatran etexilate DRUG

Probe substrate

Also known as: PRADAXA®

Dabigatran etexilate with and without ARV-471

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male and/or female participants of non-childbearing potential who are overtly healthy as determined by medical evaluation and are between the ages of 18 and 70 years, inclusive at the time of signing the informed consent document (ICD).
• Body mass index (BMI) of 17.5 to 30.5 kg/m\^2; and a total body weight \>50 kg (110 lb).
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• 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).
• Pregnant female participants, breastfeeding female participants, female participants of childbearing potential. Male participants with partners currently pregnant; male participants of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 90 days after the last dose of investigational product.
• Active bleeding or risk of bleeding including prior personal or familiar history of abnormal bleeding, hereditary or acquired coagulation or platelet disorder or abnormal coagulation test (PT/INR or PTT/aPTT greater than upper limit of normal) result at screening. Any significant risk factor for major bleeding and this may include but not limited to current or recent GI ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality, or other conditions or situations related to COVID-19 pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Use of prescription or nonprescription medications, including vitamins, dietary and herbal supplements, grapefruit/grapefruit containing products, and Seville orange/Seville orange containing products within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention or a longer washout is required for those that fall into the categories below:
• Moderate or strong cytochrome P450 (CYP) 3A / P-glycoprotein (P-gp) inducers which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
• Moderate or strong CYP3A/P-gp inhibitors which are prohibited within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
• Standard 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.

Sponsors & Collaborators

• Pfizer: lead
• Arvinas Estrogen Receptor, Inc.: collaborator

Study Sites (1)

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

Location

Related Links

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

MeSH Terms

Interventions

Dabigatran

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 6, 2023
• Study Start: January 27, 2023
• Primary Completion: March 15, 2023
• Study Completion: April 19, 2023
• Last Updated: August 16, 2024
• Results First Posted: August 16, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)