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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05673889
• Other study ID #: C4891008
• Secondary ID: 2022-003397-23
• Status: Completed
• Phase: Phase 1
• Start date: January 27, 2023
• Est. completion date: April 19, 2023

Study information

• Verified date: May 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 19, 2023
• Est. primary completion date: April 19, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• ARV-471
Experimental
• Dabigatran etexilate
Probe substrate

Locations

Country	Name	City	State
Belgium	Brussels Clinical Research Unit	Brussels	Bruxelles-capitale, Région DE

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Arvinas Estrogen Receptor, Inc.

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed concentration (Cmax) of dabigatran when dabigatran etexilate is administered alone		Period 1- Day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post-dose
Primary	Maximum observed concentration (Cmax) of dabigatran when dabigatran etexilate is administered after ARV-471		Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post-dose
Primary	Area under the curve from time zero to extrapolated infinite time [AUC (0 - 8)] of dabigatran when dabigatran etexilate is administered alone	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	Period 1- Day 1 Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post-dose
Primary	Area under the curve from time zero to extrapolated infinite time [AUC (0 - 8)] of dabigatran when dabigatran etexilate is administered after ARV-471	AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).	Period 2 - Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48 hours post-dose
Secondary	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. 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.	Time the participant provides informed consent through and including follow-up contact occurring 28 to 35 calendar days after the last administration of the study intervention.
Secondary	Number of Participants With Clinical Laboratory Abnormalities	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, cystatin C);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.	Baseline up to Period 2 Day 3
Secondary	Number of Participants With Electrocardiogram (ECG) Abnormalities	ECG abnormalities criteria include a) a post dose QTcF is increased by >60 ms from the baseline and is >450 ms; or b) an absolute QTcF value is >500ms for any scheduled ECG.	Baseline up to Period 2 Day 3
Secondary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Blood pressure and pulse rate will be performed following at least a 5-minute rest in a supine position.	Baseline up to Period 2 Day 3

External Links

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