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

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05441215
• Other study ID #: C4671039
• Secondary ID: 2022-001020-15
• Status: Completed
• Phase: Phase 1
• Start date: December 12, 2022
• Est. completion date: December 15, 2023

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 15, 2023
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• nirmatrelvir
nirmatrelvir/ritonavir
• ritonavir
nirmatrelvir/ritonavir

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit - Brussels	Brussels	Bruxelles-capitale, Région DE

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Participants reporting treatment emergent adverse events		Baseline to 28 days after last dose
Secondary	Participants reporting abnormal clinical laboratory lab tests		Baseline to 28 days after last dose
Secondary	Participants reporting abnormal vital signs		Baseline to 28 days after last dose
Secondary	Participants reporting abnormal physical examination results		Baseline to 28 days after last dose
Secondary	Participants reporting abnormal electrocardiograms		Baseline to 28 days after last dose

External Links

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