Healthy Participants
Conditions
Keywords
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), Lactation, COVID-19, Breastfeeding, Protease Inhibitor
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.
Interventions
DRUGnirmatrelvir
nirmatrelvir/ritonavir
DRUGritonavir
nirmatrelvir/ritonavir
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Observed Concentration of Nirmatrelvir in Breast Milk Over the Dosing Interval | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The maximum observed concentration and was directly observed from data. |
| Time to Reach Cmax of Nirmatrelvir in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Cmax was defined as maximum observed concentration of nirmatrelvir in breast milk. |
| Area Under the Concentration-Time Profile From Time Zero to End of Dosing Interval for Nirmatrelvir in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Area under the concentration curve for nirmatrelvir in breast milk from time 0 to end of dosing interval. |
| Terminal Half-Life of Nirmatrelvir in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The time measured for the breast milk nirmatrelvir concentration to decrease by one half. |
| The Average Steady State Concentration of Nirmatrelvir in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The average concentration across time and can be calculated by dividing AUCtau by time. AUCtau was defined area under the concentration curve from time 0 to end of dosing interval. |
| The Amount of Nirmatrelvir Excreted in Breast Milk Over the Dosing Interval Tau | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The amount of nirmatrelvir excreted into breast milk over the dosing interval. |
| The Percent of Amount of Nirmatrelvir Excreted in Breast Milk Over The Dosing Interval Tau | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The percent of nirmatelvir excreted in breast milk to amount of breast milk over the dosing interval . |
| Breast Milk Clearance of Nirmatrelvir | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Clearance was defined as the apparent volume (Liter) of breast milk completely cleared the nirmatrelvir per hour. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Maximum Observed Concentration of Ritonavir in Breast Milk Observed Over the Dosing Interval | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The maximum observed concentration and was directly observed from data. |
| Time to Reach Cmax of Ritonavir in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Cmax was defined as maximum observed concentration of ritonavir in breast milk. |
| Area Under the Concentration-Time Profile for Ritonavir in Breast Milk From Time Zero to End of Dosing Interval | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Area under the concentration curve for ritonavir in breast milk from time 0 to end of dosing interval. |
| Half-Life of Ritonavir in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The time measured for the breast milk ritonavir concentration to decrease by one half. |
| The Average Steady State Concentration of Ritonavir in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The average concentration across time and can be calculated by dividing AUCtau by time. AUCtau was defined area under the concentration curve from time 0 to end of dosing interval. |
| The Amount of Ritonavir Excreted in Breast Milk Over the Dosing Interval Tau | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The amount of ritonavir excreted into breast milk over the dosing interval. |
| The Percent of Ritonavir Excreted in Breast Milk Over The Dosing Interval Tau | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The percent of ritonavir excreted in breast milk to amount of breast milk over the dosing interval. |
| Breast Milk Clearance of Ritonavir | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Clearance was defined as the apparent volume (L) of breast milk completely cleared the ritonavir per hour. |
| The Maximum Observed Concentration of Nirmatrelvir in Plasma Observed Over the Dosing Interval | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The maximum observed concentration and was directly observed from data. |
| The Maximum Observed Concentration of Ritonavir in Plasma Observed Over the Dosing Interval | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The maximum observed concentration and was directly observed from data. |
| Area Under the Concentration-Time Profile for Nirmatrelvir in Plasma From Time Zero to End of Dosing Interval | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Area under the concentration curve for nirmatrelvir in breast milk from time 0 to end of dosing interval. |
| Area Under the Concentration-Time Profile for Ritonavir in Plasma From Time Zero to End of Dosing Interval | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Area under the concentration curve for ritonavir in plasma from time 0 to end of dosing interval. |
| Half-Life of Nirmatrelvir in Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The time measured for the plasma nirmatrelvir concentration to decrease by one half. |
| Half-Life of Ritonavir in Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The time measured for the plasma ritonavir concentration to decrease by one half. |
| The Minimum Plasma Concentration of Nirmatrelvir Observed Over the Dosing Interval | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The minimum observed concentration and was directly observed from data. |
| The Minimum Plasma Concentration of Ritonavir Observed Over the Dosing Interval | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The minimum observed concentration and was directly observed from data. |
| Time to Reach Cmax of Nirmatrelvir in Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Cmax was defined as maximum observed concentration of nirmatrelvir in plasma. |
| Time to Reach Cmax of Ritonavir in Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Cmax was defined as maximum observed concentration of ritonavir in plasma. |
| Apparent Clearance of Nirmatrelvir From Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Clearance was defined as the apparent volume (L) of plasma completely cleared the nirmatrelvir per hour. |
| Apparent Clearance of Ritonavir From Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Clearance was defined as the apparent volume (L) of plasma completely cleared the ritonavir per hour. |
| Apparent Volume of Nirmatrelvir Distribution | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose was influenced by the fraction absorbed. |
| Apparent Volume of Ritonavir Distribution | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose was influenced by the fraction absorbed. |
| The Average Steady State Concentration of Nirmatrelvir in Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The average concentration across time and can be calculated by dividing AUCtau by time. AUCtau was defined area under the concentration curve from time 0 to end of dosing interval. |
| The Average Steady State Concentration of Ritonavir in Plasma | At 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 18, 24, 32, 40, 48 Hours Post Dose on Day 2 | The average concentration across time and can be calculated by dividing AUCtau by time. AUCtau was defined area under the concentration curve from time 0 to end of dosing interval. |
| Daily (24 Hour) Amount of Nirmatrelvir Excreted in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Amount of nirmatrelvir excreted in breast milk in 24 hours. |
| Daily (24 Hour) Amount of Ritonavir Excreted in Breast Milk | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Amount of ritonavir excreted in breast milk in 24 hours. |
| Milk to Plasma Ratio of Nirmatrelvir for AUCtau During Dosing Interval | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The ratio of area under the concentration-time profile for nirmatrelvir in milk to those in plasma from time zero to end of dosing interval. |
| Milk to Plasma Ratio of Ritonavir for AUCtau During Dosing Interval | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The ratio of area under the concentration-time profile for ritonavir in milk to those in plasma from time zero to end of dosing interval. |
| Milk to Plasma Ratio of Nirmatrelvir for Cmax During Dosing Interval | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The ratio of the maximum concentration of nirmatrelvir in breast milk to those in plasma observed over the dosing interval. |
| Milk to Plasma Ratio of Ritonavir for Cmax During Dosing Interval | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | The ratio of the maximum concentration of ritonavir in breast milk to those in plasma observed over the dosing interval. |
| Body Weight Normalized Infant Dose (BWNID) of Nirmatrelvir in mg/kg/Day | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | BWNID = MPAUCtau \* Cav \* 150 mL/kg/day, where 150 mL/kg/day\^2 is the standardized milk consumption for an infant. MPAUCtau: Milk to plasma ratio for AUCtau. Cav: Average concentration. |
| BWNID of Ritonavir in mg/kg/Day | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | BWNID = MPAUCtau \* Cav \* 150 mL/kg/day, where 150 mL/kg/day\^2 is the standardized milk consumption for an infant. MPAUCtau: Milk to plasma ratio for AUCtau. Cav: Average concentration. |
| Body Weight Normalized Maternal Dose (BWNMD) of Nirmatrelvir in mg/kg/Day | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Maternal dose in mg/day (300 mg BID = 600 mg/day for nirmatrelvir and 100 mg BID = 200 mg/day for ritonavir) / maternal weight in kg at screening. |
| BWNMD of Ritonavir in mg/kg/Day | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | Maternal dose in mg/day (300 mg BID = 600 mg/day for nirmatrelvir and 100 mg BID = 200 mg/day for ritonavir) / maternal weight in kg at screening. |
| Infant Dose Expressed As % of Body Weight Normalized Maternal Dose (BWNIDPCM) for Nirmatrelvir | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | BWNIDPCM = 100 \* BWNID / BWNMD. |
| BWNIDPCM for Ritonavir | At Day -1 (24 Hours Prior to Dosing on Day 1), Pre-dose on Day 1, 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 Hours Post-dose on Day 2 | BWNIDPCM = 100 \* BWNID / BWNMD. |
| Number of Participants With Treatment Emergent Adverse Events | From the first dose of study treatment on Day 1 to up to 28 days after the last dose of study intervention on Day 2 (maximum to 30 days) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs might arise from symptoms or other complaints reported to the investigator by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative), or they might arise from clinical findings of the investigator or other healthcare providers (clinical signs, test results, etc.). TEAEs were those with initial onset or increasing in severity after the first dose of study treatment. |
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | At Screening (Day -28 to Day -2), Day -1, and Day 4 | The laboratory abnormality parameters included urinalysis: urine bilirubin (\>=1), urine hemoglobin (\>=1) and leukocyte esterase (\>=1). |
| Number of Participants With Vital Signs Abnormalities | At Screening (Day -28 to Day -2), Pre-dose and 12 Hours post-dose on Day 1, Pre-dose and 48 Hours Post-dose on Day 2 | Single supine blood pressure (BP), and pulse rate (PR) were performed following approximately a 5-minute rest in a supine position. BP, and PR assessments will be performed after collection of electrocardiogram (ECGs) and prior to collection of blood draws if scheduled at the same time. Vital signs abnormality included supine systolic BP \<90mmHg. |
| Number of Participants With ECG Abnormalities | At Screening (from Day -28 to Day -2) | Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) were collected. All ECG assessments were made after at least a 5-minute rest in a supine position and prior to any blood draws or vital sign measurements. |
| Number of Participants With Physical Examination Abnormalities | At Screening (from Day -28 to Day -2) or Day -1 | Physical examination included height, weight and body mass index (BMI, BMI = weight \[kg\] / height \[m\^2\]) obtained for eligibility criteria. Physical examination abnormalities: BMI \<17.5 kg/m\^2; and a total body weight \<=50 kg (110 lb). |
Countries
Belgium
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Pre-assignment details
Eleven participants were screened, of which 3 failed at screening. All the 8 participants who met the eligibility criteria were enrolled and assigned to the study treatment and treated with Nirmatrelvir 300 mg and Ritonavir 100 mg.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.50 Years STANDARD_DEVIATION 6.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race: White | 8 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
None listed