A Study to Learn About the Medicine (PF-07321332 or Nirmatrelvir/Ritonavir) in Healthy Lactating Women

A PHASE I, MULTIPLE DOSE, OPEN-LABEL PHARMACOKINETIC STUDY OF NIRMATRELVIR/RITONAVIR IN HEALTHY LACTATING WOMEN

The main purpose of this study is to measure the level of active ingredient of the study medicine (nirmatrelvir) that is secreted in human breast milk when it is given to healthy breastfeeding women. The study medicine consists of two medicines, nirmatrelvir and ritonavir. We are seeking female participants who are:

• Actively breast-feeding (lactating) at least 12 weeks postpartum;
• Age between 18 to 55 years and not currently pregnant;
• Have a Body Mass Index (BMI): 17.5 kg/m2; and a total body weight >50 kg (110 lb).

Participants will take the study medicine by mouth for a total of 3 times over 2 days (2 morning doses and 1 evening dose) at the study clinic. We will periodically collect breast milk from day 2 to 4 to measure the level of nirmatrelvir and ritonavir in it. A safety follow up call will be conducted around 28-35 days from the last dose to monitor any reactions participants may have to the study medicine.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: nirmatrelvir; Drug: ritonavir

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy lactating females who are actively breast-feeding or expressing breast milk, at least 12 weeks post-partum and not currently pregnant between 18 and 55 years old
• Body Mass Index (BMI): 17.5 kg/m2; and a total body weight >50 kg (110 lb)
• Infants of women enrolled in the study must be able to feed successfully from a bottle or other age-appropriate alternative feeding method prior to the start of the study and must be able to tolerate infant formula if the mother does not have a supply of stored breast milk sufficient to cover the duration of the study
• Participants must be willing to temporarily discontinue breast feeding their infants for a total of 4.5 days (108 hours)
• Participants must be willing to regularly pump breasts throughout the study and express milk according to a schedule designed to maintain lactation throughout the study period

Exclusion Criteria:

• Positive test result (RT-PCR) for SARS-CoV-2 infection at the time of screening or Day -1
• Evidence or history of clinically significant findings
• History of febrile illness or mastitis within 5 days prior to the first dose of study medication
• Participants who have received a COVID-19 vaccine within 7 days before screening or admission, or who are to be vaccinated with a COVID-19 vaccine at any time during the study confinement period
• History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed
• Abnormal vital signs such as blood pressure, 12-lead electrocardiogram
• History of alcohol abuse and/or illicit drug use, tobacco use in excess of 5 cigarettes/day or 2 chews/day
• Blood donation within 60 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nirmatrelvir/ritonavir; nirmatrelvir/ritonavir will be given by mouth two times a day as a tablet	Drug: nirmatrelvir; nirmatrelvir/ritonavir; Other Names: PF-07321332/ritonavir; Drug: ritonavir; nirmatrelvir/ritonavir; Other Names: PF-07321332/ritonavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Breastmilk Concentration (Cmax) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Time to Reach Maximum Breastmilk Concentration (Tmax) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Area under the breastmilk concentration time profile from time 0 to the time of the end of the dosing interval (tau) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Terminal phase half life (t½) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Average breastmilk concentration (Cav) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Amount excreted in breast milk over the dosing interval (Aetau) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Percent of dose excreted in breast milk during the dosing interval (Aetau %) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Breast milk clearance (CLbm) of nirmatrelvir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Tmax of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Area under the breastmilk concentration time profile from time 0 to the time of the end of the dosing interval (Auc tau) of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
t½ of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Cav of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Aetau of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Aetau % of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
CLbm of ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Cmax of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Cav of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Pre-dose concentration (Ctrough) of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Tmax of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
AUC tau of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Minimum Observed Breastmilk Concentration (Cmin) of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
t½ of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Apparent plasma clearance (CL/F) of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Apparent volume of distribution (Vz/F) of nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Daily (24 hour) amount of nirmatrelvir excreted in breast milk (Ae 24bm)	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Breast milk to plasma ratio for AUC tau (MPAUC tau) for both nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Breast milk to plasma ratio for AUC tau (MPCmax during dosing interval tau) for both nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
CLbm for both nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Milk to plasma ratio (M/P) of both nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Body weight normalized infant dose in μg/kg/day (BWNID) of both nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Body weight normalized maternal dose in μg/kg/day (BWNMD) of both nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Infant dose expressed as % of body weight normalized maternal dose (BWNIDPCM) of both nirmatrelvir and ritonavir	Day 2 (0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours) and Day 3 (18, 24, 32, 40 hours) Day 4 (48 hours)
Participants reporting treatment emergent adverse events	Baseline to 28 days after last dose
Participants reporting abnormal clinical laboratory lab tests	Baseline to 28 days after last dose
Participants reporting abnormal vital signs	Baseline to 28 days after last dose
Participants reporting abnormal physical examination results	Baseline to 28 days after last dose
Participants reporting abnormal electrocardiograms	Baseline to 28 days after last dose

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Actual): December 15, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2); Lactation; Breastfeeding; Protease Inhibitor
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Nirmatrelvir
• Other Study ID Numbers: C4671039; 2022-001020-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No