Clinical trial NCT03634345: Drug Drug Interaction Study Evaluating the Effect of Fluvoxamine or Fluconazole on PK and Safety of PF-04965842.
Official title: A PHASE 1, OPEN-LABEL, RANDOMIZED, FIXED-SEQUENCE, PARALLEL-COHORT STUDY TO ESTIMATE THE EFFECT OF FLUVOXAMINE OR FLUCONAZOLE, ON THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF A SINGLE DOSE OF PF-04965842 IN HEALTHY SUBJECTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dermatitis, Atopic
Keywords: Atopic dermatitis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-08-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: A Phase 1, Open Label, Parallel-Cohort, Randomized, Fixed Sequence Study To Evaluate The Pharmacokinetic Drug Drug Interaction Between PF-04965842 and Fkuvoxamine (cohort 1) or Fluconazole (Cohort 2) in healthy subjects.

Detailed description: A phase 1 study to evaluate the effect of fluvoxamine (a strong CYP2C19 and moderate CYP3A inhibitor) or fluconazole (a strong CYP2C19, moderate CYP2C9 and CYP3A inhibitor) on the pharmacokinetics, safety and tolerability of PF-04965842 in healthy subjects.

This study will be a Phase 1, open label, randomized, fixed-sequence, parallel-cohort study drug-drug interaction study. The study includes 2 periods:

In Period 1: all subjects will receive one single oral dose of 100 mg PF 04965842 tablet. (Treatment A). PK will be evaluated in the first 72 hours post adminstration of PF 04965842.

In Period 2:

* Cohort 1: subjects will receive fluvoxamine (immediate release tablet 50 mg) once daily for 9 consecutive days; on Day 8, subjects will receive a single oral dose of 100 mg PF 04965842 approximately 3 hours after fluvoxamine administration. (Treatment B). PK will be evaluated in the first 72 hours post administration of PF 04965842.
* Cohort 2: subjects will receive fluconazole capsule(s) once daily for 7 consecutive days (400 mg on Day 1 and 200 mg on Day 2-7 in Period 2); on Day 5, subjects will receive a single oral dose of 100 mg PF 04965842 approximately 1 hour after fluconazole administration. (Treatment C). PK will be evaluated in the first 72 hours post administration of PF 04965842.

Eligibility criteria: Inclusion Criteria:

* Healthy male or female subjects.
* Body mass index (BMI) of 17.5 to 30.5 kg/m2 and a total body weight \>50 kg (110 lb).

Exclusion Criteria:

* Evidence or history of hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease.
* Evidence or history of clinically significant dermatological condition (eg, contact dermatitis or psoriasis) or visible rash present during physical examination.
* History of hypersensitivity to or intolerance of fluvoxamine and/or fluconazole.
* Any condition possibly affecting drug absorption.
* A positive urine drug test.
* Screening supine systolic BP \<90 mm Hg or 140 mm Hg following at least 5 minutes of supine rest OR Screening supine diastolic BP \<50 mm Hg or 90 mm Hg following at least 5 minutes of supine rest.
* Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception.

Primary outcomes:
measure: Plasma Cmax for PF 04965842
timeFrame: First 72 hours post PF-04965842 administration in Period 1 and Period 2
measure: AUCinf for PF-04965842
timeFrame: First 72 hours post PF-04965842 administration in Period 1 and Period 2
Secondary outcomes:
measure: Number of subjects with Adverse events (AEs)
timeFrame: Screening up to 28 Days after the Last Dose of PF 04965842
measure: Number of subjects with laboratory tests findings of potential clinical importance
timeFrame: Screening up to 7-14 Days after the Last Dose of PF 04965842 in Period 2
measure: Number of Subjects with clinically significant abnormal Vital Signs
timeFrame: Screening up to 7-14 Days after the Last Dose of PF 04965842 in Period 2
measure: Number of Subjects with Electrocardiograms (ECGs) findings of potential clinical importance
timeFrame: Screening up to 7-14 Days after the Last Dose of PF 04965842 in Period 2
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Wang X, Dowty ME, Wouters A, Tatulych S, Connell CA, Le VH, Tripathy S, O'Gorman MT, Winton JA, Yin N, Valdez H, Malhotra BK. Assessment of the Effects of Inhibition or Induction of CYP2C19 and CYP2C9 Enzymes, or Inhibition of OAT3, on the Pharmacokinetics of Abrocitinib and Its Metabolites in Healthy Individuals. Eur J Drug Metab Pharmacokinet. 2022 May;47(3):419-429. doi: 10.1007/s13318-021-00745-6. Epub 2022 Feb 28.
citation: Wojciechowski J, Malhotra BK, Wang X, Fostvedt L, Valdez H, Nicholas T. Population Pharmacokinetics of Abrocitinib in Healthy Individuals and Patients with Psoriasis or Atopic Dermatitis. Clin Pharmacokinet. 2022 May;61(5):709-723. doi: 10.1007/s40262-021-01104-z. Epub 2022 Jan 21.