Clinical trial NCT05441215: A Study to Learn About the Medicine (PF-07321332 or Nirmatrelvir/Ritonavir) in Healthy Lactating Women
Official title: A PHASE I, MULTIPLE DOSE, OPEN-LABEL PHARMACOKINETIC STUDY OF NIRMATRELVIR/RITONAVIR IN HEALTHY LACTATING WOMEN
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)
Lactation
COVID-19
Breastfeeding
Protease Inhibitor
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-07-01
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Breastmilk Concentration (Cmax) of nirmatrelvir
timeFrame: 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)
measure: Time to Reach Maximum Breastmilk Concentration (Tmax) of nirmatrelvir
timeFrame: 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)
measure: Area under the breastmilk concentration time profile from time 0 to the time of the end of the dosing interval (tau) of nirmatrelvir
timeFrame: 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)
measure: Terminal phase half life (t½) of nirmatrelvir
timeFrame: 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)
measure: Average breastmilk concentration (Cav) of nirmatrelvir
timeFrame: 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)
measure: Amount excreted in breast milk over the dosing interval (Aetau) of nirmatrelvir
timeFrame: 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)
measure: Percent of dose excreted in breast milk during the dosing interval (Aetau %) of nirmatrelvir
timeFrame: 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)
measure: Breast milk clearance (CLbm) of nirmatrelvir
timeFrame: 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 outcomes:
measure: Cmax of ritonavir
timeFrame: 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)
measure: Tmax of ritonavir
timeFrame: 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)
measure: Area under the breastmilk concentration time profile from time 0 to the time of the end of the dosing interval (Auc tau) of ritonavir
timeFrame: 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)
measure: t½ of ritonavir
timeFrame: 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)
measure: Cav of ritonavir
timeFrame: 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)
measure: Aetau of ritonavir
timeFrame: 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)
measure: Aetau % of ritonavir
timeFrame: 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)
measure: CLbm of ritonavir
timeFrame: 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)
measure: Cmax of nirmatrelvir and ritonavir
timeFrame: 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)
measure: Cav of nirmatrelvir and ritonavir
timeFrame: 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)
measure: Pre-dose concentration (Ctrough) of nirmatrelvir and ritonavir
timeFrame: 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)
measure: Tmax of nirmatrelvir and ritonavir
timeFrame: 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)
measure: AUC tau of nirmatrelvir and ritonavir
timeFrame: 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)
measure: Minimum Observed Breastmilk Concentration (Cmin) of nirmatrelvir and ritonavir
timeFrame: 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)
measure: t½ of nirmatrelvir and ritonavir
timeFrame: 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)
measure: Apparent plasma clearance (CL/F) of nirmatrelvir and ritonavir
timeFrame: 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)
measure: Apparent volume of distribution (Vz/F) of nirmatrelvir and ritonavir
timeFrame: 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)
measure: Daily (24 hour) amount of nirmatrelvir excreted in breast milk (Ae 24bm)
timeFrame: 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)
measure: Breast milk to plasma ratio for AUC tau (MPAUC tau) for both nirmatrelvir and ritonavir
timeFrame: 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)
measure: Breast milk to plasma ratio for AUC tau (MPCmax during dosing interval tau) for both nirmatrelvir and ritonavir
timeFrame: 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)
measure: CLbm for both nirmatrelvir and ritonavir
timeFrame: 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)
measure: Milk to plasma ratio (M/P) of both nirmatrelvir and ritonavir
timeFrame: 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)
measure: Body weight normalized infant dose in μg/kg/day (BWNID) of both nirmatrelvir and ritonavir
timeFrame: 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)
measure: Body weight normalized maternal dose in μg/kg/day (BWNMD) of both nirmatrelvir and ritonavir
timeFrame: 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)
measure: Infant dose expressed as % of body weight normalized maternal dose (BWNIDPCM) of both nirmatrelvir and ritonavir
timeFrame: 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)
measure: Participants reporting treatment emergent adverse events
timeFrame: Baseline to 28 days after last dose
measure: Participants reporting abnormal clinical laboratory lab tests
timeFrame: Baseline to 28 days after last dose
measure: Participants reporting abnormal vital signs
timeFrame: Baseline to 28 days after last dose
measure: Participants reporting abnormal physical examination results
timeFrame: Baseline to 28 days after last dose
measure: Participants reporting abnormal electrocardiograms
timeFrame: Baseline to 28 days after last dose
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: