Drug-Drug Interaction Study Assessing Effect of Carbamazepine on PF-07321332 Boosted With Ritonavir

NCT04962230 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4671014
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participant

Keywords

Drug-drug interaction; Carbamazepine; CYP3A4 inducer

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of PF-07321332

  Cmax was defined as maximum observed plasma concentration and can be observed directly from data.

  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

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07321332

  AUCinf was defined as area under the concentration-time curve from time 0 to infinity and was calculated as AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.

  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 (16)

• Cmax of Ritonavir

  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

• AUCinf of Ritonavir

  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

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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)

• Number of Participants With Laboratory Abnormalities

  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

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  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

Study Arms (2)

Period 1

EXPERIMENTAL

PF-07321332/ritonavir orally as a single dose

Drug: PF-07321332/ritonavir

Period 2

EXPERIMENTAL

Carbamazepine + PF-07321332/ritonavir orally.

Drug: Carbamazepine; Drug: PF 07321332/ritonavir

Interventions

PF-07321332/ritonavir DRUG

PF-07321332/ritonavir administered orally as a single dose on Day 1, Period 1

Period 1

Carbamazepine DRUG

In Period 2, Days 1-3, participants will receive low-dose of carbamazepine twice daily (BID), then a titrated mid-dose of carbamazepine BID on Days 4-7, and finally maintaining carbamazepine at the high-dose on Days 8-15.

Period 2

PF 07321332/ritonavir DRUG

In Period 2, Day 14, participants will receive a single dose of PF-07321332/ritonavir orally.

Period 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Positive test reverse-transcriptase polymerase chain reaction (RT-PCR) result for SARS-CoV-2 infection at the time of Screening or Day -1.
• Subjects shown to carry or be positive for human leukocyte antigen (HLA)-B\*1502 and HLA-A\*3101
• Participants taking monoamine oxidase inhibitors (MAOIs) should discontinue MAOI for a minimum of 14 days prior to dosing in the current study.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Publications (2)

• 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.

  PMID: 17346248 BACKGROUND

• 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.

  PMID: 9812178 RESULT

Related Links

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

MeSH Terms

Interventions

nirmatrelvir and ritonavir drug combination; Carbamazepine; Ritonavir

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: July 10, 2021
• First Posted: July 14, 2021
• Study Start: July 15, 2021
• Primary Completion: October 9, 2021
• Study Completion: October 9, 2021
• Last Updated: October 10, 2023
• Results First Posted: October 10, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)