Clinical trial NCT04962230: Drug-Drug Interaction Study Assessing Effect of Carbamazepine on PF-07321332 Boosted With Ritonavir
Official title: A PHASE 1, OPEN-LABEL, FIXED SEQUENCE, 2-PERIOD CROSSOVER STUDY TO ESTIMATE THE EFFECT OF CARBAMAZEPINE ON THE PHARMACOKINETICS OF PF-07321332 BOOSTED WITH RITONAVIR IN HEALTHY PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participant
Keywords: Drug-drug interaction
Carbamazepine
CYP3A4 inducer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-07-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a Phase 1, fixed sequence, 2-period study to estimate the effect of a strong CYP3A4 inducer, carbamazepine, on the PK of PF-07321332 and ritonavir in healthy participants. A total of approximately 12 healthy male and/or female participants will be enrolled into the study.
Primary purpose: BASIC_SCIENCE

Brief summary: This is a drug-drug interaction study to assess the effects of a single dose of PF-07321332/ritonavir after multiple dose administrations of carbamazepine. Pharmacokinetic (PK) will be evaluated for PF-07321332 and ritonavir. Carbamazepine is being utilized as a cytochrome P450 3A4 (CYP3A4) inducer.


Eligibility criteria: Inclusion Criteria:

1. Female participants of childbearing potential must have a negative (urine or serum) pregnancy test.
2. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).

Exclusion Criteria:

1. Positive test reverse-transcriptase polymerase chain reaction (RT-PCR) result for SARS-CoV-2 infection at the time of Screening or Day -1.
2. Subjects shown to carry or be positive for human leukocyte antigen (HLA)-B\*1502 and HLA-A\*3101
3. Participants taking monoamine oxidase inhibitors (MAOIs) should discontinue MAOI for a minimum of 14 days prior to dosing in the current study.
4. Hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, vaginal ring, and postcoital contraceptive methods) and hormone replacement therapy must have been discontinued at least 28 days prior to the first dose of investigational product. Depo Provera must be discontinued at least 6 months prior to the first dose of study treatment.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of PF-07321332
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07321332
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Secondary outcomes:
measure: Cmax of Ritonavir
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: AUCinf of Ritonavir
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Screening up to Day 3 in Period 1; Day 1 up to 35 days from administration of the final dose of study intervention or early termination/discontinuation in Period 2 (maximum of approximately 12 weeks)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Screening, Day -1 prior to dosing, and Day 2 in Period 1; Days 3, 6, 9, 12, 16 or early termination/discontinuation in Period 2
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: Screening and Day 1 pre-dose, and at 1.5, 8, and 24 hours post dose in Period 1; Days 2, 3, 4, 6, 8, 10, 12, Day 14 pre-dose, and at 1.5, 8, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
timeFrame: Screening and Day 1 pre-dose, and at 1.5, 8, and 24 hours post dose in Period 1; Days 2, 3, 4, Day 14 pre-dose, and at 1.5, 8, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07321332
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Apparent Oral Clearance (CL/F) of PF-07321332
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Apparent Volume of Distribution (Vz/F) of PF-07321332
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Terminal Half-Life ( t1/2) of PF-07321332
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Tmax of Ritonavir
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: AUClast of Ritonavir
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: CL/F of Ritonavir
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: Vz/F of Ritonavir
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
measure: t1/2 of Ritonavir
timeFrame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Andreasen AH, Brosen K, Damkier P. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4. Epilepsia. 2007 Mar;48(3):490-6. doi: 10.1111/j.1528-1167.2007.00924.x.
citation: Hsu A, Granneman GR, Bertz RJ. Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet. 1998 Oct;35(4):275-91. doi: 10.2165/00003088-199835040-00002.