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The purpose of this study is to evaluate the relative bioavailability (rBA) of the Form 2 film-coated tablet of PF-07799933 intended for use in future studies compared to the current Form 1 tablet of PF-07799933 used in Phase 1 studies. Additionally this study will also evaluate the effect of a high-fat meal on the plasma pharmacokinetics (PK), i.e, the rBA compared to overnight fasting, of PF-07799933 and PF-07799544 following concurrent single-dose oral administration of Form 2 film-coated tablet formulation of PF-07799933 with PF-07799544. Finally, this study will also assess the impact of a proton pump inhibitor (a type of acid reducing agent) on PF-07799933 PK of the Form 2 film-coated tablet formulation. These data will be used to inform administration of PF-07799933 and PF-07799544 with food and acid reducing agents in future clinical trials.
This is a Phase 1, open-label, randomized, single-dose, 2-cohort study: a three period two sequence crossover (Relative Bioavailability and Food Effect) cohort in healthy adult participants, and a two-period single sequence cohort (Proton Pump Inhibitor) in healthy adult participants. Cohort 1 of this study, which has 3 periods, will evaluate the impact of the Form 2 film-coated tablet of PF-07799933 (test formulation) compared to the Form 1 tablet of PF-07799933 (reference formulation) used in the C4901001 and C4761001 Phase 1 studies (Period 1 and Period 2). This cohort (Cohort 1) will also evaluate the effect of a high fat meal on plasma pharmacokinetics (ie, the relative bioavailability compared to overnight fasting) of the Form 2 film-coated tablet of PF-07799933 and of PF-07799544 following concurrent single-dose administrations of 300 mg of PF 07799933 and the optimized dose identified from an ongoing clinical study (either 7.5 or 12 mg) of PF 07799544 to healthy adult participants (Period 3). Cohort 2, which has two periods, will evaluate the plasma pharmacokinetics of PF-07799933 before (Period 1) and after administration of the proton pump inhibitor rabeprazole (20 mg BID for 3 days and once in the morning for the last dose [seven total doses]) (Period 2). Cohort 2 will be conducted using the Form 2 film-coated tablet of PF-07799933 in both periods.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-07799933 Form 1 Tablet Arm with PF-07799544 Fasted | Experimental | Cohort 1 Period 1: Participants receive PF-07799933 tablets in Combination With PF-07799544 |
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| PF-07799933 Form 2 Film-Coated Tablet Arm with PF-07799544 Fasted | Experimental | Cohort 1 Period 2: Participants receive PF-07799933 film-coated tablets in Combination With PF-07799544 |
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| PF-07799933 Form 2 Film-Coated Tablet Arm with PF-07799544 under Fed Conditions | Experimental | Cohort 1 Period 3: Participants receive PF-07799933 film-coated tablets in Combination With PF-07799544 following a High-Fat Meal |
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| PF-07799933 Form 2 Tablet Arm | Experimental | Cohort 2 Period 1: Participants receive PF-07799933 film-coated tablets |
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| PF-07799933 Form 2 Tablet Arm following Rabeprazole Pretreatment | Experimental | Cohort 2 Period 1: Participants receive PF-07799933 film-coated tablets following rabeprazole treatment |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-07799933 tablets with PF-07799544 fasted | Drug | Participants receive Form 1 in a single dose of tablet in a single dose combination fasted |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799933 Form 1 tablet when dosed in combination with PF-07799544 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose | |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799933 Form 2 film-coated tablet when dosed in combination with PF-07799544 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose | |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799933 Form 1 tablet when dosed in combination with PF-07799544 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose | |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799933 Form 2 film-coated tablet when dosed in combination with PF-07799544 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose | |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799933 Form 1 tablet when dosed in combination with PF-07799544 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose | |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799933 Form 2 film-coated tablet when dosed in combination with PF-07799544 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose | |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799933 Form 2 film-coated tablet when dosed in combination with PF-07799544 under fed conditions |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with treatment-emergent adverse events (AEs) | To evaluate the safety and tolerability of PF 07799933 and PF-07799544 when co-administered in healthy adult participants including a new formulation of PF 07799933 and following a high-fat meal. AEs as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
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Inclusion Criteria
Exclusion Criteria
ALT, AST, Bilirubin ≥1.5× ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN, Hemoglobin ≤ 11 g/dL ANC ≤ 1.5 × 109/L, Platelets ≤ 150,000/mm3/.
- History of alcohol abuse or repeated binge drinking and/or any other illicit drug use or dependence within 6 months of screening.
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Clinical Research Unit - New Haven | New Haven | Connecticut | 06511 | United States |
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| 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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| PF-07799933 film-coated tablets with PF-07799544 fasted | Drug | Participants receive Form 2 in a single dose of tablet in a single dose combination fasted |
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| PF-07799933 film-coated tablets with PF-07799544 fed | Drug | Participants receive Form 2 in a single dose of tablet in a single dose combination in the fed state |
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| PF-07799933 film-coated tablets fasted | Drug | Participants receive Form 2 in a single dose of tablet fasted |
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| PF-07799933 film-coated tablets following rabeprazole pretreatment fasted | Drug | Participants receive Form 2 in a single dose of tablet following rabeprazole pre-treatment fasted |
|
| 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799933 Form 2 film-coated tablet when dosed in combination with PF-07799544 under fed conditions | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799933 Form 2 film-coated tablet when dosed in combination with PF-07799544 under fed conditions | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799544 tablet when dosed in combination with Form 2 film-coated tablet of PF-07799933 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799544 tablet when dosed in combination with Form 2 film-coated tablet of PF-07799933 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799544 tablet when dosed in combination with Form 2 film-coated tablet of PF-07799933 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799544 tablet when dosed in combination with Form 1 tablet of PF-07799933 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799544 tablet when dosed in combination with Form 1 tablet of PF-07799933 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799544 tablet when dosed in combination with Form 1 tablet of PF-07799933 fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799544 tablet when dosed in combination with Form 2 film-coated tablet of PF-07799933 under fed conditions | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799544 tablet when dosed in combination with Form 2 film-coated tablet of PF-07799933 under fed conditions | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799544 tablet when dosed in combination with Form 2 film-coated tablet of PF-07799933 under fed conditions | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799933 Form 2 film-coated tablet when dosed fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799933 Form 2 film-coated tablet when dosed fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799933 Form 2 film-coated tablet when dosed fasted | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799933 Form 2 film-coated tablet when dosed fasted following rabeprazole pretreatment | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Area Under the Curve From Time Zero to The Last Measured Time Point (AUClast) for PF-07799933 Form 2 film-coated tablet when dosed fasted following rabeprazole pretreatment | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) for PF-07799933 Form 2 film-coated tablet when dosed fasted following rabeprazole pretreatment | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose |
| Number of participants with treatment-emergent laboratory abnormalities. | To evaluate the safety and tolerability of PF 07799933 and PF-07799544 when co-administered in healthy adult participants including a new formulation of PF 07799933 and following a high-fat meal. Laboratory abnormalities as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
| Number of participants with treatment-emergent vital sign abnormalities. | To evaluate the safety and tolerability of PF 07799933 and PF-07799544 when co-administered in healthy adult participants including a new formulation of PF 07799933 and following a high-fat meal. Vital sign abnormalities as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
| Number of participants with treatment-emergent electrocardiogram (ECG) abnormalities. | To evaluate the safety and tolerability of PF 07799933 and PF-07799544 when co-administered in healthy adult participants including a new formulation of PF 07799933 and following a high-fat meal. ECG abnormalities as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
| Number of participants with treatment-emergent physical exam abnormalities. | To evaluate the safety and tolerability of PF 07799933 and PF-07799544 when co-administered in healthy adult participants including a new formulation of PF 07799933 and following a high-fat meal. Physical exam abnormalities as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
| To evaluate the safety and tolerability of PF-07799933 when coadministered with and without rabeprazole in healthy adult participants: Number of participants with treatment-emergent AEs. | AEs characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
| To evaluate the safety and tolerability of PF-07799933 when coadministered with and without rabeprazole in healthy adult participants: Number of participants with treatment-emergent laboratory abnormalities. | Laboratory abnormalities as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
| To evaluate the safety and tolerability of PF-07799933 when coadministered with and without rabeprazole in healthy adult participants: Number of participants with treatment-emergent ECG abnormalities. | ECG abnormalities as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |
| To evaluate the safety and tolerability of PF-07799933 when coadministered with and without rabeprazole in healthy adult participants: Number of participants with physical exam abnormalities. | Physical exam abnormalities as characterized by type, frequency, severity, and relationship to study intervention. | From Baseline up to Day 35 |