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

AN INTERVENTIONAL, PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY TO EVALUATE THE EFFECT OF A SINGLE ORAL DOSE OF ARV-471 (PF-07850327) ON THE PHARMACOKINETICS OF DABIGATRAN IN HEALTHY PARTICIPANTS

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ARV-471; Drug: Dabigatran etexilate

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran etexilate with and without ARV-471; 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; Experimental; Other Names: PF-07850327; Drug: Dabigatran etexilate; Probe substrate; Other Names: PRADAXA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)	An AE is any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship with the study intervention. SAE is defined as one of the following: is fatal or life threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. AEs include all SAEs and non-SAEs.	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)	Following parameters were analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid, cystatinC); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose); urinalysis (dipstick [decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, bilirubin], microscopy. Abnormality was determined at the investigator's discretion.	Baseline (Period 1 Day -1) up to Period 2 Day 3 (8 days)
Number of Participants With Clinically Significant Vital Signs	Vital signs (blood pressure and pulse rate) were obtained with participant following at least a 5-minute rest in a supine position. Clinical significance of vital signs was determined at the investigator's discretion.	Baseline (Period 1 Day 1) up to Period 2 Day 3 (7 days)
Number of Participants With Electrocardiogram (ECG) Abnormalities	ECG abnormalities criteria include a) a postdose QTc corrected using Fridericia's formula (QTcF) increased by >60 millisecond (ms) from the baseline and the absolute QTcF value >450 ms; or b) an absolute QTcF value >500 ms for any scheduled ECG.	Baseline (Period 1 Day 1) up to Period 2 Day 3 (7 days)

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Arvinas Estrogen Receptor, Inc.
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2023
• Primary Completion (Actual): March 15, 2023
• Study Completion (Actual): April 19, 2023

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: C4891008; 2022-003397-23 (EudraCT Number: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No