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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Period 1 | Experimental | PF-07321332/ritonavir orally as a single dose |
|
| Period 2 | Experimental | Carbamazepine + PF-07321332/ritonavir orally. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-07321332/ritonavir | Drug | PF-07321332/ritonavir administered orally as a single dose on Day 1, Period 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | Cmax was defined as maximum observed plasma concentration and can be observed directly from data. | 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 |
| 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of Ritonavir | Cmax was defined as maximum observed plasma concentration and can be observed directly from data. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer New Haven Clinical Research Unit | New Haven | Connecticut | 06511 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17346248 | Background | Andreasen AH, Brosen K, Damkier P. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4. Epilepsia. 2007 Mar;48(3):490-6. doi: 10.1111/j.1528-1167.2007.00924.x. | |
| 9812178 | Result | Hsu A, Granneman GR, Bertz RJ. Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet. 1998 Oct;35(4):275-91. doi: 10.2165/00003088-199835040-00002. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PF-07321332 300 mg/Ritonavir 100 mg |
| |||||||||||||
| Carbamazepine+PF-07321332/Ritonavir |
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All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | Cmax was defined as maximum observed plasma concentration and can be observed directly from data. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 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 |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Period1: PF-07321332 300 mg/Ritonavir 100 mg | 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). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Excessive cerumen production | Ear and labyrinth disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 2, 2021 | Sep 8, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 21, 2021 | Sep 8, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000719967 | nirmatrelvir and ritonavir drug combination |
| D002220 | Carbamazepine |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D003984 | Dibenzazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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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.
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| Carbamazepine | Drug | 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. |
|
| PF 07321332/ritonavir | Drug | In Period 2, Day 14, participants will receive a single dose of PF-07321332/ritonavir orally. |
|
| 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. | 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 |
| 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. | 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) |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 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. | 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 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. | 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 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. | 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 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. | 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 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. | 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 |
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| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| OG001 | Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | 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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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | 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 |
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| Secondary | Cmax of Ritonavir | Cmax was defined as maximum observed plasma concentration and can be observed directly from data. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | 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) |
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| 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. | The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | 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 |
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| 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. | The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | 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 |
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| 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. | The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | 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 |
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| 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. | 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. | Posted | Median | Full Range | hour (hr) | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour (L/hr) | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter (L) | 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 |
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| 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. | 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. | Posted | Mean | Standard Deviation | hours (hr) | 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 |
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| 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. | 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. | Posted | Median | Full Range | hour (hr) | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | 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 |
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| 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. | 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. | Posted | Mean | Standard Deviation | hr | 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 |
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| 0 |
| 12 |
| 0 |
| 12 |
| 4 |
| 12 |
| EG001 | Period2: Carbamazepine + PF-07321332 300 mg/Ritonavir 100 mg | 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). | 0 | 12 | 0 | 12 | 9 | 12 |
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Asymptomatic COVID-19 | Infections and infestations | MedDRA v24.0 | Non-systematic Assessment |
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| Transaminases increased | Investigations | MedDRA v24.0 | Non-systematic Assessment |
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| Altered pitch perception | Nervous system disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Sciatica | Nervous system disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Poor quality sleep | Psychiatric disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Polyuria | Renal and urinary disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v24.0 | Non-systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA v24.0 | Non-systematic Assessment |
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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.
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Participants with treatment related adverse events |
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| Participants with treatment related serious adverse events |
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| Erythrocytes (10^6/mm^3) <0.8x LLN |
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| Lymphocytes (10^3/mm^3) <0.8x LLN |
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| Neutrophils (10^3/mm^3) <0.8x LLN |
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| Eosinophils/Leukocytes (%) >1.2x upper limit of normal (ULN) |
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| Monocytes/Leukocytes (%) >1.2x ULN |
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| Alanine Aminotransferase (U/L) >3.0x ULN |
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| Sodium (milliequivalent per liter (mEq/L)) <0.95x LLN |
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| Urobilinogen (EU/dL) ≥1 |
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| Fibrinogen (mg/dL) >1.25x Baseline |
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| URINE Hemoglobin ≥1 |
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| Supine diastolic blood pressure change ≥20mmHg decrease |
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| Supine pulse rate value <40 beats per minute(bpm) |
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| Supine pulse rate value >120 bpm |
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| Supine systolic blood pressure value <90mmHg |
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| Supine systolic blood pressure change ≥30mmHg decrease |
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| Supine systolic blood pressure change ≥30mmHg increase |
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| QRS duration, aggregate value ≥140 msec |
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| QRS duration, aggregate percent change ≥50% |
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| QTCF interval, aggregate value >450 msec and ≤480 msec |
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| QTCF interval, aggregate value >480 msec and ≤500 msec |
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| QTCF interval, aggregate value >500 msec |
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| QTCF interval, aggregate change ≥30 msec and ≤60 msec |
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| QTCF interval, aggregate change >60 msec |
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