Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05441215 | A Study to Learn About the Medicine (PF-07321332 or Nirmatrelvir/Ritonavir) in Healthy Lactating Women | PHASE1 | COMPLETED | 8 | — | — | Dec 12, 2022 | Dec 15, 2023 | May 1, 2026 | 1 | Belgium |
| NCT05339334 | A Study to Learn About the Study Medicine PF-07321332 and Ritonavir in Adult Healthy Chinese Participants. | PHASE1 | COMPLETED | 14 | — | — | Mar 10, 2022 | Apr 21, 2022 | Oct 8, 2024 | 1 | China |
| NCT05129475 | Food Effect Study to Evaluate the Effect of High-Fat Meal on the Relative Bioavailability of PF-07321332 Boosted With Ritonavir in Healthy Adult Participants | PHASE1 | COMPLETED | 12 | — | — | Nov 12, 2021 | Jan 12, 2022 | Oct 5, 2023 | 1 | United States |
| NCT05064800 | PF-07321332/Ritonavir and Ritonavir on Dabigatran Study in Healthy Participants | PHASE1 | COMPLETED | 24 | — | — | Sep 21, 2021 | Dec 6, 2021 | Mar 29, 2024 | 1 | United States |
| NCT05032950 | Drug-Drug Interaction Study to Estimate the Effect of PF-07321332/Ritonavir and Ritonavir on Midazolam in Healthy Participants | PHASE1 | COMPLETED | 12 | — | — | Sep 17, 2021 | Dec 9, 2021 | Oct 4, 2023 | 1 | Belgium |
The maximum observed concentration and was directly observed from data.
Cmax was defined as maximum observed concentration of nirmatrelvir in breast milk.
Area under the concentration curve for nirmatrelvir in breast milk from time 0 to end of dosing interval.
The time measured for the breast milk nirmatrelvir concentration to decrease by one half.
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 into breast milk over the dosing interval.
The percent of nirmatelvir excreted in breast milk to amount of breast milk over the dosing interval .
Clearance was defined as the apparent volume (Liter) of breast milk completely cleared the nirmatrelvir per hour.
Cmax is maximum plasma concentration .
Cmax is maximum plasma concentration
Tmax is the time for maximum plasma concentration
Tmax is the time for maximum plasma concentration
Area under the plasma concentration-time profile from time Zero to time point on 12 hours
Area under the plasma concentration-time profile from time 0 to the time of the end of the dosing interval (tau), where tau=12 hours.
This was determined by AUCtau/tau.
Accumulation ratio for AUCtau following multiple dosing was calculated as AUCtau on Day 10 divided by AUC12 on Day 1.
Observed accumulation ratio for Cmax was calculated as Cmax on Day 10 divided by Cmax on Day 1.
This was determined by Day 10 Cmax/Day 10 Ctrough.
Apparent oral clearance. This was determined by Dose/AUCtau.
Apparent oral volume of distribution.
Terminal half-life. This was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (Clast)
Concentration at pre-dose on Day 5. Observed directly from data.
Concentration at pre-dose on Day 8. Observed directly from data.
Concentration at pre-dose on Day 10. Observed directly from data.
Concentration at 12 hour time on Day 10. Observed directly from data.
Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration was determined by linear/log trapezoidal method and reported in this outcome measure.
AUCinf was calculated by AUClast + (Clast/kel). AUClast was the area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Cmax was defined as maximum observed plasma concentration. It was observed directly from data.
Cmax was defined as maximum observed plasma concentration.
AUCinf was defined as the area under the plasma concentration-time curve from time 0 extrapolated to infinity
AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.
Cmax for midazolam following single dose administration with and without PF-07321332/ritonavir was observed directly from data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \[test\]/midazolam \[reference\] and 90% CIs) were expressed as percentages.
AUCinf for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \[test\]/midazolam \[reference\] and 90% CIs) were expressed as percentages.
AUClast for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam \[test\]/midazolam \[reference\] and 90% CIs) were expressed as percentages.
| Arm | Type | Description |
|---|---|---|
| nirmatrelvir/ritonavir | EXPERIMENTAL | nirmatrelvir/ritonavir will be given by mouth two times a day as a tablet |
| PF-07321332/ritonavir | EXPERIMENTAL | PF-07321332/ritonavir will be given by mouth two times a day for 10 days to adult Chinese healthy volunteers |
| Treatment A | EXPERIMENTAL | Single oral dose of ritonavir at -12 hours prior to PF-07321332/ritonavir dosing, followed by single oral dose of PF-07321332/ritonavir under fasted conditions. Ritonavir will continue to be dosed at 12 hours PF-07321332 dosing. |
| Treatment B | EXPERIMENTAL | Single oral dose of ritonavir at -12 hours prior to PF 07321332/ritonavir dosing, followed by single oral dose of PF-07321332/ritonavir under fed conditions. Ritonavir will continue to be dosed at 12 hours PF-07321332 dosing. |
| Treatment C | ACTIVE_COMPARATOR | Ritonavir + Dabigatran |
| Name | Type | Description |
|---|---|---|
| nirmatrelvir | DRUG | nirmatrelvir/ritonavir |
| ritonavir | DRUG | nirmatrelvir/ritonavir |
| PF-07321332/ritonavir | DRUG | PF-07321332/ritonavir will be given by mouth two times a day for 10 days |
| Dabigatran | DRUG | A single dose of Dabigatran on Day 1 |
| PF-07321332/ritonavir + Dabigatran | DRUG | PF-07321332/ritonavir twice daily (BID) for Days 1 and 2 Single dose of Dabigatran on Day 2 |
| Ritonavir + Dabigatran | DRUG | Ritonavir BID on Days 1 and 2 Single dose of Dabigatran on Day 2 |
| Midazolam | DRUG | Midazolam administered as a single dose on Day 1 |
| PF-07321332/ritonavir + Midazolam | DRUG | PF-07321332/ritonavir: Administered orally every 12 hours for a total of 9 doses on Days 1-5 Midazolam: Administered orally as a single dose on Day 5 |
| Ritonavir + Midazolam | DRUG | Ritonavir: Administered orally every 12 hours for a total of 9 doses on Day1-5. Midazolam: Administered orally as a single dose on Day 5 |
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 i...