Healthy Participant
Conditions
Keywords
Drug-drug interaction, Carbamazepine, CYP3A4 inducer
Brief summary
This is a drug-drug interaction study to assess the effects of a single dose of PF-07321332/ritonavir after multiple dose administrations of carbamazepine. Pharmacokinetic (PK) will be evaluated for PF-07321332 and ritonavir. Carbamazepine is being utilized as a cytochrome P450 3A4 (CYP3A4) inducer.
Interventions
PF-07321332/ritonavir administered orally as a single dose on Day 1, Period 1
DRUGCarbamazepine
In Period 2, Days 1-3, participants will receive low-dose of carbamazepine twice daily (BID), then a titrated mid-dose of carbamazepine BID on Days 4-7, and finally maintaining carbamazepine at the high-dose on Days 8-15.
DRUGPF 07321332/ritonavir
In Period 2, Day 14, participants will receive a single dose of PF-07321332/ritonavir orally.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is a Phase 1, fixed sequence, 2-period study to estimate the effect of a strong CYP3A4 inducer, carbamazepine, on the PK of PF-07321332 and ritonavir in healthy participants. A total of approximately 12 healthy male and/or female participants will be enrolled into the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Female participants of childbearing potential must have a negative (urine or serum) pregnancy test. 2. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
Exclusion criteria
1. Positive test reverse-transcriptase polymerase chain reaction (RT-PCR) result for SARS-CoV-2 infection at the time of Screening or Day -1. 2. Subjects shown to carry or be positive for human leukocyte antigen (HLA)-B\*1502 and HLA-A\*3101 3. Participants taking monoamine oxidase inhibitors (MAOIs) should discontinue MAOI for a minimum of 14 days prior to dosing in the current study. 4. Hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, vaginal ring, and postcoital contraceptive methods) and hormone replacement therapy must have been discontinued at least 28 days prior to the first dose of investigational product. Depo Provera must be discontinued at least 6 months prior to the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | Cmax was defined as maximum observed plasma concentration and can be observed directly from data. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07321332 | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | AUCinf was defined as area under the concentration-time curve from time 0 to infinity and was calculated as AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Screening up to Day 3 in Period 1; Day 1 up to 35 days from administration of the final dose of study intervention or early termination/discontinuation in Period 2 (maximum of approximately 12 weeks) | An Adverse event (AE) was any untoward medical occurrence in a participant. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity, congenital anomaly/birth. An AE was considered treatment-emergent AE (TEAE) if the event occurred during the on-treatment period. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. A treatment-related SAE was a treatment-related AE and was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Relatedness to study drug was assessed by the investigator. |
| Number of Participants With Laboratory Abnormalities | Screening, Day -1 prior to dosing, and Day 2 in Period 1; Days 3, 6, 9, 12, 16 or early termination/discontinuation in Period 2 | Safety laboratory assessments included hematology, urinalysis, and clinical chemistry. All the safety laboratory samples were collected following at least a 4 hour fast. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Screening and Day 1 pre-dose, and at 1.5, 8, and 24 hours post dose in Period 1; Days 2, 3, 4, 6, 8, 10, 12, Day 14 pre-dose, and at 1.5, 8, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | Vital signs including single supine blood pressure and pulse rate were performed following at least a 5 minute rest in a supine position. Blood pressure (BP) and pulse rate (PR) assessments were performed after collection of electrocardiograms (ECGs) and prior to collection of blood draws if planned together. Respiratory rate (RR) was also evaluated. |
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | Screening and Day 1 pre-dose, and at 1.5, 8, and 24 hours post dose in Period 1; Days 2, 3, 4, Day 14 pre-dose, and at 1.5, 8, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | All ECG assessments (triplicate) were made after at least a 10 minute rest in a supine position and prior to any blood draws or vital sign measurements. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | Tmax was defined as time to reach maximum observed plasma concentration and can be observed directly from data as time of first occurrence. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07321332 | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of last observed quantifiable plasma concentration (Clast) and was determined by Linear/Log trapezoidal method. |
| Apparent Oral Clearance (CL/F) of PF-07321332 | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | CL/F was defined as apparent clearance. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time. |
| Cmax of Ritonavir | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | Cmax was defined as maximum observed plasma concentration and can be observed directly from data. |
| Terminal Half-Life ( t1/2) of PF-07321332 | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | t1/2 was defined as the time measured for the plasma concentration of drug to decrease by one half. t1/2 is calculated as Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline was used in the regression. |
| Tmax of Ritonavir | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | Tmax was defined as time to reach maximum observed plasma concentration and can be observed directly from data as time of first occurrence. |
| AUClast of Ritonavir | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of Clast and was determined by Linear/Log trapezoidal method. |
| CL/F of Ritonavir | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | CL/F was defined as apparent clearance. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time. |
| Vz/F of Ritonavir | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | Vz/F was defined as apparent volume of distribution. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| t1/2 of Ritonavir | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | t1/2 was defined as the time measured for the plasma concentration of drug to decrease by one half. t1/2 is calculated as Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline was used in the regression. |
| Apparent Volume of Distribution (Vz/F) of PF-07321332 | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | Vz/F was defined as apparent volume of distribution. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| AUCinf of Ritonavir | Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2 | AUCinf was defined as area under the concentration-time curve from time 0 to infinity and was calculated as AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. |
Countries
United States
Participant flow
Pre-assignment details
This study consisted of 2 periods. Twelve participants were enrolled into the study. All 12 participants were treated and 10 completed the study. Two participants discontinued from the study in Period 2.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants were enrolled and received study drug. In Period 1, participants received PF-07321332 300 mg with ritonavir 100 mg administered orally as a single dose starting at approximately 0800 hours (±2 hours) on Day 1 following an overnight fast of at least 10 hours. PF-07321332 and ritonavir were dosed simultaneously (within no more than 5 minutes of each other). In Period 2, participants received carbamazepine 100 mg twice daily (BID) administered orally on Days 1, 2, and 3, and titrated up to 200 mg BID on Days 4, 5, 6, and 7, and eventually titrated up to and maintained at 300 mg BID stably in the rest of Period 2 from Days 8 to 15. Carbamazepine was administered with or without food on all study days except on Study Day 14 when dosing was under fasting conditions. There were no water restrictions for carbamazepine dosing. On Period 2 Day 14, participants received PF-07321332 300 mg administered orally with ritonavir 100 mg starting at approximately 0815 to 0830 hours (±10 minutes), approximately 15 to 30 min after the carbamazepine dose. PF-07321332 and ritonavir were dosed simultaneously (within no more than 5 minutes of each other). | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Carbamazepine+PF-07321332/Ritonavir | Adverse Event | 1 |
| Carbamazepine+PF-07321332/Ritonavir | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Customized 18 to 25 years old (18-25) | 1 Participants |
| Age, Customized 26 to 35 years old (26-35) | 4 Participants |
| Age, Customized 36 to 45 years old (36-45) | 2 Participants |
| Age, Customized Less than 18 years old （<18) | 0 Participants |
| Age, Customized more than 45 years old （>45） | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 9 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07321332
AUCinf was defined as area under the concentration-time curve from time 0 to infinity and was calculated as AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for AUCinf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07321332 | 23010 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07321332 | 10280 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 58 |
p-value: 0.0590% CI: [33.77, 58.65]Mixed Models Analysis
Primary
Maximum Observed Plasma Concentration (Cmax) of PF-07321332
Cmax was defined as maximum observed plasma concentration and can be observed directly from data.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | 2210 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | 1300 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 43 |
p-value: 0.0590% CI: [47.04, 68.62]Mixed Models Analysis
Secondary
Apparent Oral Clearance (CL/F) of PF-07321332
CL/F was defined as apparent clearance. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Apparent Oral Clearance (CL/F) of PF-07321332 | 13.06 Liter per hour (L/hr) | Geometric Coefficient of Variation 23 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Apparent Oral Clearance (CL/F) of PF-07321332 | 29.17 Liter per hour (L/hr) | Geometric Coefficient of Variation 58 |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-07321332
Vz/F was defined as apparent volume of distribution. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for Vz/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Apparent Volume of Distribution (Vz/F) of PF-07321332 | 109.4 Liter (L) | Geometric Coefficient of Variation 38 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Apparent Volume of Distribution (Vz/F) of PF-07321332 | 157.2 Liter (L) | Geometric Coefficient of Variation 69 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07321332
AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of last observed quantifiable plasma concentration (Clast) and was determined by Linear/Log trapezoidal method.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for AUClast.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07321332 | 22450 ng*hr/mL | Geometric Coefficient of Variation 23 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07321332 | 10050 ng*hr/mL | Geometric Coefficient of Variation 58 |
p-value: 0.0590% CI: [33.99, 58.5]Mixed Models Analysis
Secondary
AUCinf of Ritonavir
AUCinf was defined as area under the concentration-time curve from time 0 to infinity and was calculated as AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for AUCinf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | AUCinf of Ritonavir | 3599 ng*hr/mL | Geometric Coefficient of Variation 47 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | AUCinf of Ritonavir | 677.6 ng*hr/mL | Geometric Coefficient of Variation 61 |
p-value: 0.0590% CI: [13.32, 20.6]Mixed Models Analysis
Secondary
AUClast of Ritonavir
AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of Clast and was determined by Linear/Log trapezoidal method.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for AUClast.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | AUClast of Ritonavir | 3414 ng*hr/mL | Geometric Coefficient of Variation 47 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | AUClast of Ritonavir | 466.2 ng*hr/mL | Geometric Coefficient of Variation 104 |
p-value: 0.0590% CI: [9.28, 17.99]Mixed Models Analysis
Secondary
CL/F of Ritonavir
CL/F was defined as apparent clearance. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | CL/F of Ritonavir | 27.78 L/hr | Geometric Coefficient of Variation 48 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | CL/F of Ritonavir | 147.6 L/hr | Geometric Coefficient of Variation 61 |
Secondary
Cmax of Ritonavir
Cmax was defined as maximum observed plasma concentration and can be observed directly from data.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Cmax of Ritonavir | 359.3 ng/mL | Geometric Coefficient of Variation 46 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Cmax of Ritonavir | 96.07 ng/mL | Geometric Coefficient of Variation 71 |
p-value: 0.0590% CI: [18.76, 34.91]Mixed Models Analysis
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs including single supine blood pressure and pulse rate were performed following at least a 5 minute rest in a supine position. Blood pressure (BP) and pulse rate (PR) assessments were performed after collection of electrocardiograms (ECGs) and prior to collection of blood draws if planned together. Respiratory rate (RR) was also evaluated.
Time frame: Screening and Day 1 pre-dose, and at 1.5, 8, and 24 hours post dose in Period 1; Days 2, 3, 4, 6, 8, 10, 12, Day 14 pre-dose, and at 1.5, 8, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure value <50 mmHg | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure change ≥30mmHg decrease | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure change ≥20mmHg increase | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure change ≥20mmHg decrease | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine pulse rate value <40 beats per minute(bpm) | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine pulse rate value >120 bpm | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure value <90mmHg | 1 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure change ≥30mmHg increase | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure change ≥20mmHg decrease | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure value <50 mmHg | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure value <90mmHg | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine pulse rate value >120 bpm | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure change ≥30mmHg increase | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine pulse rate value <40 beats per minute(bpm) | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine diastolic blood pressure change ≥20mmHg increase | 1 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Supine systolic blood pressure change ≥30mmHg decrease | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
All ECG assessments (triplicate) were made after at least a 10 minute rest in a supine position and prior to any blood draws or vital sign measurements.
Time frame: Screening and Day 1 pre-dose, and at 1.5, 8, and 24 hours post dose in Period 1; Days 2, 3, 4, Day 14 pre-dose, and at 1.5, 8, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | PR interval, aggregate percent change ≥25/50% | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate value >480 msec and ≤500 msec | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QRS duration, aggregate percent change ≥50% | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate value >500 msec | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QRS duration, aggregate value ≥140 msec | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate change ≥30 msec and ≤60 msec | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate value >450 msec and ≤480 msec | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate change >60 msec | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | PR interval, aggregate value ≥300 milliseconds (msec) | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate change >60 msec | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | PR interval, aggregate value ≥300 milliseconds (msec) | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | PR interval, aggregate percent change ≥25/50% | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QRS duration, aggregate value ≥140 msec | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QRS duration, aggregate percent change ≥50% | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate value >450 msec and ≤480 msec | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate value >480 msec and ≤500 msec | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate value >500 msec | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | QTCF interval, aggregate change ≥30 msec and ≤60 msec | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
Safety laboratory assessments included hematology, urinalysis, and clinical chemistry. All the safety laboratory samples were collected following at least a 4 hour fast.
Time frame: Screening, Day -1 prior to dosing, and Day 2 in Period 1; Days 3, 6, 9, 12, 16 or early termination/discontinuation in Period 2
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes (%) >1.2x upper limit of normal (ULN) | 1 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Lymphocytes (10^3/mm^3) <0.8x LLN | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Erythrocytes (10^6/mm^3) <0.8x LLN | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Neutrophils (10^3/mm^3) <0.8x LLN | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes (%) >1.2x ULN | 1 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Fibrinogen (mg/dL) >1.25x Baseline | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Alanine Aminotransferase (U/L) >3.0x ULN | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Hematocrit (%) <0.8x LLN | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Sodium (milliequivalent per liter (mEq/L)) <0.95x LLN | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | URINE Hemoglobin ≥1 | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Urobilinogen (EU/dL) ≥1 | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Hemoglobin (g/dL) <0.8x lower limit of normal (LLN) | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Urobilinogen (EU/dL) ≥1 | 1 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Hemoglobin (g/dL) <0.8x lower limit of normal (LLN) | 1 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Hematocrit (%) <0.8x LLN | 1 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Erythrocytes (10^6/mm^3) <0.8x LLN | 1 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Eosinophils/Leukocytes (%) >1.2x upper limit of normal (ULN) | 4 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Fibrinogen (mg/dL) >1.25x Baseline | 1 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | URINE Hemoglobin ≥1 | 3 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Lymphocytes (10^3/mm^3) <0.8x LLN | 2 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Neutrophils (10^3/mm^3) <0.8x LLN | 1 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Monocytes/Leukocytes (%) >1.2x ULN | 5 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Alanine Aminotransferase (U/L) >3.0x ULN | 4 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Laboratory Abnormalities | Sodium (milliequivalent per liter (mEq/L)) <0.95x LLN | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An Adverse event (AE) was any untoward medical occurrence in a participant. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity, congenital anomaly/birth. An AE was considered treatment-emergent AE (TEAE) if the event occurred during the on-treatment period. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. A treatment-related SAE was a treatment-related AE and was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Relatedness to study drug was assessed by the investigator.
Time frame: Screening up to Day 3 in Period 1; Day 1 up to 35 days from administration of the final dose of study intervention or early termination/discontinuation in Period 2 (maximum of approximately 12 weeks)
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with all-causality adverse events | 4 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with all-causality serious adverse events | 0 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with treatment related adverse events | 1 Participants |
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with treatment related serious adverse events | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with treatment related serious adverse events | 0 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with all-causality adverse events | 9 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with treatment related adverse events | 6 Participants |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with all-causality serious adverse events | 0 Participants |
Secondary
t1/2 of Ritonavir
t1/2 was defined as the time measured for the plasma concentration of drug to decrease by one half. t1/2 is calculated as Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline was used in the regression.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The pharmacokinetic (PK) parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for t1/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | t1/2 of Ritonavir | 6.149 hr | Standard Deviation 2.2413 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | t1/2 of Ritonavir | 3.345 hr | Standard Deviation 0.79964 |
Secondary
Terminal Half-Life ( t1/2) of PF-07321332
t1/2 was defined as the time measured for the plasma concentration of drug to decrease by one half. t1/2 is calculated as Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline was used in the regression.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for t1/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Terminal Half-Life ( t1/2) of PF-07321332 | 6.053 hours (hr) | Standard Deviation 1.7939 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Terminal Half-Life ( t1/2) of PF-07321332 | 3.845 hours (hr) | Standard Deviation 0.99642 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332
Tmax was defined as time to reach maximum observed plasma concentration and can be observed directly from data as time of first occurrence.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The pharmacokinetic (PK) parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 | 3.00 hour (hr) |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 | 1.50 hour (hr) |
Secondary
Tmax of Ritonavir
Tmax was defined as time to reach maximum observed plasma concentration and can be observed directly from data as time of first occurrence.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Tmax of Ritonavir | 3.98 hour (hr) |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Tmax of Ritonavir | 1.98 hour (hr) |
Secondary
Vz/F of Ritonavir
Vz/F was defined as apparent volume of distribution. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Day 1 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post dose in Period 1; Day 14 pre-dose, and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose or early termination/discontinuation in Period 2
Population: The analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. Number of participants analyzed represents the number of participants contributing to the summary statistics for Vz/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period1: PF-07321332 300 mg/Ritonavir 100 mg | Vz/F of Ritonavir | 234.0 L | Geometric Coefficient of Variation 36 |
| Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | Vz/F of Ritonavir | 697.5 L | Geometric Coefficient of Variation 51 |