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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-508171-36-00 | Registry Identifier | CTIS (EU) |
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This study has four parts: Part A, Part B, Part C, and Part D.
The purpose of Part A of this study is to learn about the:
The purpose of Part B of this study is to understand the effect of multiple doses of PF-07393893 on the amount of midazolam when given as a single dose by mouth.
The purpose of part C of this study is to understand how PF-07293893 is changed in the body and how much PF-07293893 and it's changed forms are being removed in urine and feces after a single dose given to single participants.
The purpose of Part D is to understand the effect of multiple doses of PF-07293893 on the amount of glycogen (storage form of glucose) in the muscle of healthy participants.
Part B, C and D will be done if the results of Part A support further study of PF-07293893.
The study is seeking participants who:
For a given participant in Part A, the total study is going to last up to about 11 weeks. This includes from the time of selection till the last follow-up phone call. The participants will be selected if they are fit for the study 28 days before the first dose of the study medicines. Participants who are selected will be admitted to the study site on Day 1 for around 18 days. Following discharge, participants will return for an on-site follow-up visit 7 to 10 days after receiving the final dose of the study medicine. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given.
For a given participant in Part B, the total study is going to last up to about 11 weeks. This study consists of 4 periods. Participants will be admitted to the study site on Day 1 and discharged on Day 3 in period 4. Following discharge, participants will return for an on-site follow-up visit 7 to 10 days after receiving the final dose of the study medicine in period 4. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given in period 4.
For a given participant in Part C, the total study is going to last up to about 9 weeks. Participants will be admitted to the study site on Day 1. The participants will be discharged on Day 11 after giving the study medicine. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given.
For a given participant in Part D, the total study is going to last up to about 11 weeks. The participants will be selected if they are fit for the study 28 days before the first dose of the study medicines. Participants who are selected will be admitted to the study site on Day -3 for around 17 days. Following discharge, participants will return for an on-site follow-up visit 7 to 10 days after receiving the final dose of the study medicine. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-07293893 and Placebo (Cohort 1) | Experimental | Dose level 1: Multiple dose administration of PF-07293893 and placebo over 14 days in healthy participants; 6 participants will receive PF-07293893 and 2 will receive placebo. |
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| PF-07293893 and Placebo (Cohort 2) | Experimental | Dose level 2: Multiple dose administration of PF-07293893 and placebo over 14 days in healthy participants; 6 participants will receive PF-07293893 and 2 will receive placebo. |
|
| PF-07293893 and Placebo (Cohort 3) | Experimental | Dose level 3: Multiple dose administration of PF-07293893 and placebo over 14 days in healthy participants; 6 participants will receive PF-07293893 and 2 will receive placebo. |
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| PF-07293893 and Placebo (Cohort 4) | Experimental | Dose level 4: Multiple dose administration of PF-07293893 and placebo over 14 days in healthy participants; 6 participants will receive PF-07293893 and 2 will receive placebo. |
|
| PF-07293893 and Placebo (Cohort 5) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-07293893 | Drug | PF-07293893 will be administered as tablets every day (QD) over 14 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A:Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Baseline up to 35 days after last dose of study intervention (approximately 11 weeks). | |
| Part A: Number of Participants With Clinical Laboratory Abnormalities | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks). | |
| Part A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks). | |
| Part A: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks). | |
| Part A: Number of Participants With Clinically-Significant Change From Baseline in Physical Examination Findings | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks). | |
| Part A: Number of Participants With Clinically-Significant Change From Baseline in Neurological Examination Findings | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks). | |
| Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose on Period 1/Day 1 | |
| Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post dose on Period 2/Day 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose on Day 1 | |
| Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose on Day 14 |
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Inclusion Criteria:
Exclusion Criteria:
Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
CK > 2.5 x ULN.
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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 | ||
| Yale University/Magnetic Resonance Research Center (MRRC) |
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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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| ID | Term |
|---|---|
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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Dose level 5: Multiple dose administration of PF-07293893 and placebo over 14 days in healthy participants; 6 participants will receive PF-07293893 and 2 will receive placebo.
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| PF-07293893 and Placebo (Cohort 6, Optional) | Experimental | Dose level 6: Multiple dose administration of PF-07293893 and placebo over 14 days in healthy participants; 6 participants will receive PF-07293893 and 2 will receive placebo. |
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| Midazolam drug-drug interaction (Cohort 7, Optional) | Experimental | Drug-drug interaction assessment of pharmacokinetics interaction in PF-07293893 and midazolam |
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| Metabolism and elimination of PF-07293893 (Cohort 8, Optional) | Experimental | Determination of excretion routes and metabolite profiling of PF-07293893. |
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| Skeletal muscle imaging (Cohort 8, optional) | Experimental | Evaluation of the effect of 14-days of daily PF-07293893 on skeletal muscle glycogen in healthy adult participants |
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| Placebo | Drug | Placebo will be administered as tablets; QD over 14 days |
|
| Midazolam | Drug | Single doses of Midazolam will be administered as oral solution alone and in combination with PF-07293893 |
|
| Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post dose on Period 4/Day 1 |
| Part B: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose on Period 1/Day 1 |
| Part B: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post dose on Period 2/Day 2 |
| Part B: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post dose on Period 4/Day 1 |
| Part B: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose on Period 1/Day 1 |
| Part B: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post dose on Period 2/Day 2 |
| Part B: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam | Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post dose on Period 4/Day 1 |
| Part C: Total recovery of drug-related material in urine and feces separately, and both routes combined, expressed as a percent of total dose administered. | Predose to Day 11 |
| Part D: Change from baseline in glycogen on Day 14 as measured by 13C MRS of skeletal muscle | Day 14 (last day of dosing) |
| Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (tau) (AUCtau) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose on Day 1 |
| Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (tau) (AUCtau) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose on Day 14 |
| Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose on Day 1 |
| Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose on Day 14 |
| Part A: Amount of PF-07293893 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | On Day 14, urine collection for PK to occur over 0-tau, according to dosing frequency (ie, 0-12 hours for 12 hour dosing interval; 0-24 hours for 24 hour dosing interval) |
| Part A: Percentage of Dose of PF-07293893 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | On Day 14, urine collection for PK to occur over 0-tau, according to dosing frequency (ie, 0-12 hours for 12 hour dosing interval; 0-24 hours for 24 hour dosing interval) |
| Part A: Renal Clearance of PF-07293893 | On Day 14, urine collection for PK to occur over 0-tau, according to dosing frequency (ie, 0-12 hours for 12 hour dosing interval; 0-24 hours for QD dosing interval) |
| Part B: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Baseline up to 35 days after last dose of study intervention (approximately 10 weeks) |
| Part B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks) |
| Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks) |
| Part B: Number of Participants With Clinical Laboratory Abnormalities | Baseline up to 10 days after last dose of study intervention (approximately 7 weeks) |
| Part B: Number of Participants With Clinically-Significant Change From Baseline in Physical Examination Findings | Baseline up to 35 days after last dose of study intervention (approximately 10 weeks) |
| Part C: Maximum Observed Plasma Concentration (Cmax) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose |
| Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose |
| Part C: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose |
| Part C: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose |
| Part C: Terminal half life (t1/2) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose |
| Part C: Apparent clearance (CL/F) of PF-07293893 from plasma | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose |
| Part C: Apparent volume of distribution (Vz/F) of PF-07293893 | predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose |
| Part D: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Baseline up to 35 days after last dose of study intervention (approximately 11 weeks) |
| Part D: Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to 10 days after last dose of study intervention (approximately 8 weeks) |
| Part D: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings | Baseline up to 10 days after last dose of study intervention (approximately 8 weeks) |
| Part D: Number of Participants With Clinical Laboratory Abnormalities | Baseline up to 10 days after last dose of study intervention (approximately 8 weeks) |
| New Haven |
| Connecticut |
| 06511 |
| United States |
| Pfizer Clinical Research Unit - Brussels | Brussels | Bruxelles-capitale, Région de | B-1070 | Belgium |
| D006571 | Heterocyclic Compounds |