Study of PF-04965842 Effect on Dabigatran Pharmacokinetics in Healthy Participants

NCT03742336 | Completed Phase 1 FDA Drug

• 2 other identifiers: B74510262018-003579-36
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, randomized, 2 way crossover, single dose, open label study of the effect of PF 04965842 on dabigatran PK in healthy participants. Participants will be randomized to 1 of 2 treatment sequences as described below. A total of 20 healthy male and/or female participants will be enrolled in the study so that 10 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods that are each 3 days in duration. The total duration of participation from the Screening Visit to Day 7 will be a maximum of 35 days and from the Screening Visit to Follow-up Contact/Visit will be a maximum of 70 days.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• AUCinf of dabigatran

  Area under the curve from time zero to extrapolated infinite time for dabigatran

  36 hours after dabigatran administration in Period 1 and 2

• Plasma Cmax of dabigatran

  Maximum observed plasma concentration for dabigatran

  36 hours after dabigatran administration in Period 1 and 2

Secondary Outcomes (7)

• AUClast of dabigatran

  36 hours after dabigatran administration in Period 1 and 2

• Tmax of dabigatran

  36 hours after dabigatran administration in Period 1 and 2

• t1/2 of dabigatran

  36 hours after dabigatran administration in Period 1 and 2

• Number of subjects with adverse events (AEs).

  Screening up to 28-35 days after the last dose of PF 04965842 in period 2

• Number of subjects with laboratory tests findings of potential clinical importance

  Screening through Day 3 of period 2

Study Arms (2)

Arm 1

EXPERIMENTAL

Single dose of dabigatran on Day 1 of Period 1 and Single dose of dabigatran + PF-04965842 on Day 1 of Period 2.

Drug: PF-04965842; Drug: Dabigatran

Arm 2

EXPERIMENTAL

Single dose of dabigatran + PF-04965842 on Day 1 of Period 1 and Single dose of dabigatran on Day 1 of Period 2.

Drug: PF-04965842; Drug: Dabigatran

Interventions

PF-04965842 DRUG

Single oral 200 mg dose of PF-04965842

Arm 1; Arm 2

Dabigatran DRUG

Single 75 mg dose of dabigatran

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Age and Sex:
• Male and female participants must be 18 to 55 years of age, inclusive, at the time of signing the informed consent document (ICD).
• Type of Participant and Disease Characteristics:
• Male and female participants who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination, laboratory tests, and ECG.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Weight:
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
• Informed Consent:
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical Conditions:
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic (including alcoholic liver disease, nonalcoholic steatohepatitis (NASH), autoimmune hepatitis, and hereditary liver diseases), psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Evidence or history of clinically significant dermatological condition (eg, atopic dermatitis or psoriasis) or visible rash present during physical examination.
• Participants, who according to the product label for dabigatran, would be at increased risk if dosed with dabigatran.
• Risks of bleeding including prior personal or familiar history of abnormal bleeding, hereditary or acquired coagulation or platelet disorder or abnormal coagulation test (prothrombin time \[PT\]/international normalized ratio \[INR\] or partial thromboplastin time \[PTT\]/activated partial thromboplastin time \[aPTT\] greater than upper limit of normal \[ULN\]) result at screening.
• Surgery planned within 4 weeks after the end of the study.
• Self reported history or risk factors for QT prolongation or torsades de pointes (eg, organic heart disease, congestive heart failure, hypokalemia, hypomagnesaemia, congenital long QT syndrome, myocardial ischemia or infarction), congenital deafness, family history of sudden death, and family history of long QT syndrome.
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus infection; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb).
• As an exception, a positive HepBsAb as a result of participant vaccination is permissible.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Prior/Concomitant Therapy:
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of investigational product.
• Prior/Concurrent Clinical Study Experience:

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Location

Related Publications (1)

• Vourvahis M, Byon W, Chang C, Le V, Diehl A, Graham D, Tripathy S, Raha N, Luo L, Mathialagan S, Dowty M, Rodrigues AD, Malhotra B. Evaluation of the Effect of Abrocitinib on Drug Transporters by Integrated Use of Probe Drugs and Endogenous Biomarkers. Clin Pharmacol Ther. 2022 Sep;112(3):665-675. doi: 10.1002/cpt.2594. Epub 2022 May 9.

  PMID: 35344588 DERIVED

Related Links

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

MeSH Terms

Interventions

abrocitinib; Dabigatran

Intervention Hierarchy (Ancestors)

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 15, 2018
• Study Start: November 21, 2018
• Primary Completion: February 18, 2019
• Study Completion: February 18, 2019
• Last Updated: February 28, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)