Trial Outcomes & Findings for Drug-Drug Interaction Study Assessing Effect of Carbamazepine on PF-07321332 Boosted With Ritonavir (NCT NCT04962230)
NCT ID: NCT04962230
Last Updated: 2023-10-10
Results Overview
Cmax was defined as maximum observed plasma concentration and can be observed directly from data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
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
Results posted on
2023-10-10
Participant Flow
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.
Participant milestones
| Measure |
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).
|
|---|---|
|
PF-07321332 300 mg/Ritonavir 100 mg
STARTED
|
12
|
|
PF-07321332 300 mg/Ritonavir 100 mg
COMPLETED
|
12
|
|
PF-07321332 300 mg/Ritonavir 100 mg
NOT COMPLETED
|
0
|
|
Carbamazepine+PF-07321332/Ritonavir
STARTED
|
12
|
|
Carbamazepine+PF-07321332/Ritonavir
COMPLETED
|
10
|
|
Carbamazepine+PF-07321332/Ritonavir
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
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).
|
|---|---|
|
Carbamazepine+PF-07321332/Ritonavir
Withdrawal by Subject
|
1
|
|
Carbamazepine+PF-07321332/Ritonavir
Adverse Event
|
1
|
Baseline Characteristics
Drug-Drug Interaction Study Assessing Effect of Carbamazepine on PF-07321332 Boosted With Ritonavir
Baseline characteristics by cohort
| Measure |
All Participants
n=12 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).
|
|---|---|
|
Age, Customized
Less than 18 years old （<18)
|
0 Participants
n=5 Participants
|
|
Age, Customized
18 to 25 years old (18-25)
|
1 Participants
n=5 Participants
|
|
Age, Customized
26 to 35 years old (26-35)
|
4 Participants
n=5 Participants
|
|
Age, Customized
36 to 45 years old (36-45)
|
2 Participants
n=5 Participants
|
|
Age, Customized
more than 45 years old （>45）
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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 2Population: 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.
Cmax was defined as maximum observed plasma concentration and can be observed directly from data.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of PF-07321332
|
2210 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 33
|
1300 nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 43
|
PRIMARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
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
|
10280 nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 58
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
Cmax was defined as maximum observed plasma concentration and can be observed directly from data.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Cmax of Ritonavir
|
359.3 ng/mL
Geometric Coefficient of Variation 46
|
96.07 ng/mL
Geometric Coefficient of Variation 71
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=8 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
AUCinf of Ritonavir
|
3599 ng*hr/mL
Geometric Coefficient of Variation 47
|
677.6 ng*hr/mL
Geometric Coefficient of Variation 61
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
In Period 2, participants received carbamazepine 100 mg 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).
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|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Participants with all-causality adverse events
|
4 Participants
|
9 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Participants with all-causality serious adverse events
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Participants with treatment related adverse events
|
1 Participants
|
6 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Participants with treatment related serious adverse events
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Screening, Day -1 prior to dosing, and Day 2 in Period 1; Days 3, 6, 9, 12, 16 or early termination/discontinuation in Period 2Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Safety laboratory assessments included hematology, urinalysis, and clinical chemistry. All the safety laboratory samples were collected following at least a 4 hour fast.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities
Hemoglobin (g/dL) <0.8x lower limit of normal (LLN)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
Hematocrit (%) <0.8x LLN
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
Erythrocytes (10^6/mm^3) <0.8x LLN
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
Lymphocytes (10^3/mm^3) <0.8x LLN
|
0 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Abnormalities
Neutrophils (10^3/mm^3) <0.8x LLN
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
Eosinophils/Leukocytes (%) >1.2x upper limit of normal (ULN)
|
1 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Abnormalities
Monocytes/Leukocytes (%) >1.2x ULN
|
1 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Abnormalities
Alanine Aminotransferase (U/L) >3.0x ULN
|
0 Participants
|
4 Participants
|
|
Number of Participants With Laboratory Abnormalities
Sodium (milliequivalent per liter (mEq/L)) <0.95x LLN
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
Urobilinogen (EU/dL) ≥1
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
Fibrinogen (mg/dL) >1.25x Baseline
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
URINE Hemoglobin ≥1
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 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 2Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine diastolic blood pressure value <50 mmHg
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine diastolic blood pressure change ≥20mmHg increase
|
0 Participants
|
1 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine diastolic blood pressure change ≥20mmHg decrease
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine pulse rate value <40 beats per minute(bpm)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine pulse rate value >120 bpm
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine systolic blood pressure value <90mmHg
|
1 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine systolic blood pressure change ≥30mmHg decrease
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Supine systolic blood pressure change ≥30mmHg increase
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 2Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
PR interval, aggregate value ≥300 milliseconds (msec)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
PR interval, aggregate percent change ≥25/50%
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
QRS duration, aggregate value ≥140 msec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
QRS duration, aggregate percent change ≥50%
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
QTCF interval, aggregate value >450 msec and ≤480 msec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
QTCF interval, aggregate value >480 msec and ≤500 msec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
QTCF interval, aggregate value >500 msec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
QTCF interval, aggregate change ≥30 msec and ≤60 msec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
QTCF interval, aggregate change >60 msec
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
Tmax was defined as time to reach maximum observed plasma concentration and can be observed directly from data as time of first occurrence.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332
|
3.00 hour (hr)
Interval 1.02 to 6.0
|
1.50 hour (hr)
Interval 0.5 to 4.0
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-07321332
|
22450 ng*hr/mL
Geometric Coefficient of Variation 23
|
10050 ng*hr/mL
Geometric Coefficient of Variation 58
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Apparent Oral Clearance (CL/F) of PF-07321332
|
13.06 Liter per hour (L/hr)
Geometric Coefficient of Variation 23
|
29.17 Liter per hour (L/hr)
Geometric Coefficient of Variation 58
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) of PF-07321332
|
109.4 Liter (L)
Geometric Coefficient of Variation 38
|
157.2 Liter (L)
Geometric Coefficient of Variation 69
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=8 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Terminal Half-Life ( t1/2) of PF-07321332
|
6.053 hours (hr)
Standard Deviation 1.7939
|
3.845 hours (hr)
Standard Deviation 0.99642
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
Tmax was defined as time to reach maximum observed plasma concentration and can be observed directly from data as time of first occurrence.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Tmax of Ritonavir
|
3.98 hour (hr)
Interval 1.48 to 4.2
|
1.98 hour (hr)
Interval 0.983 to 4.0
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=10 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
AUClast of Ritonavir
|
3414 ng*hr/mL
Geometric Coefficient of Variation 47
|
466.2 ng*hr/mL
Geometric Coefficient of Variation 104
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=8 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
CL/F of Ritonavir
|
27.78 L/hr
Geometric Coefficient of Variation 48
|
147.6 L/hr
Geometric Coefficient of Variation 61
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=8 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Vz/F of Ritonavir
|
234.0 L
Geometric Coefficient of Variation 36
|
697.5 L
Geometric Coefficient of Variation 51
|
SECONDARY outcome
Timeframe: 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 2Population: 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.
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.
Outcome measures
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 Participants
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=8 Participants
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
t1/2 of Ritonavir
|
6.149 hr
Standard Deviation 2.2413
|
3.345 hr
Standard Deviation 0.79964
|
Adverse Events
Period1: PF-07321332 300 mg/Ritonavir 100 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Period1: PF-07321332 300 mg/Ritonavir 100 mg
n=12 participants at risk
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).
|
Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg
n=12 participants at risk
In Period 2, participants received carbamazepine 100 mg 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).
|
|---|---|---|
|
Ear and labyrinth disorders
Excessive cerumen production
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Endocrine disorders
Inappropriate antidiuretic hormone secretion
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
General disorders
Vessel puncture site haematoma
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Infections and infestations
Asymptomatic COVID-19
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Investigations
Transaminases increased
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
41.7%
5/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Nervous system disorders
Altered pitch perception
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Nervous system disorders
Dysgeusia
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Nervous system disorders
Sciatica
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Psychiatric disorders
Poor quality sleep
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Renal and urinary disorders
Polyuria
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
8.3%
1/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
16.7%
2/12 • 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)
Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER