Phase 1
Completed N=109
A Study of PF-07258669 In Healthy Adult Participants
Healthy Participants
Source: ClinicalTrials.gov NCT05113940 ↗
Enrolled (actual)
109
Serious AEs
0.7%
Results posted
Oct 2024
Primary outcomePrimary: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) — 5; 8; 6; 6 Participants
Summary
Part A of this study is to evaluate safety, tolerability, and pharmacokinetics (PK) of PF-07258669 after administration of multiple ascending oral doses to healthy adult participants. Optional cohorts of healthy adult Japanese participants and/or older adult participants may also be evaluated if results in other cohorts support further evaluation. Part B of this study is a 2-period, fixed-sequence, multiple-dose, open-label design to evaluate the effect of PF-07258669 on midazolam PK in healthy adult participants. Part B will be conducted if the results of Part A support further evaluation of PF-07258669.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
5; 8; 6; 6; 9; 6 | — |
| PRIMARY Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality |
5; 6; 6; 6; 9; 5 | — |
| PRIMARY Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data |
0; 0; 1; 0; 1; 0 | — |
| PRIMARY Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone on Day 1 of Period 1 |
6.213 | — |
| PRIMARY Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 |
10.83 | — |
| PRIMARY Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 |
11.73 | — |
| PRIMARY Part B: Area Under the Plasma Concentration-Time Curve From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam Alone on Day 1 of Period 1 |
18.56 | — |
| PRIMARY Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 |
30.27 | — |
| PRIMARY Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 |
40.41 | — |
| PRIMARY Part B: Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam Alone on Day 1 of Period 1 |
19.35 | — |
| PRIMARY Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 |
32.84 | — |
| PRIMARY Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 |
41.16 | — |
| SECONDARY Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 |
19.47; 25.06; 50.41; 45.99; 131.2; 468.3 | — |
| SECONDARY Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 |
9.742; 8.352; 8.403; 7.666; 6.562; 7.803 | — |
| SECONDARY Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 |
46.27; 60.42; 113.6; 107.2; 388.1; 1207 | — |
| SECONDARY Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 |
23.16; 20.15; 18.93; 17.87; 19.42; 20.14 | — |
| SECONDARY Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 |
1.000; 1.000; 0.5830; 0.8265; 1.010; 1.000 | — |
| SECONDARY Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) |
0.004304; 0.004490; 0.01690; 0.01462; 0.04039; 0.1440 | — |
| SECONDARY Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) |
0.2152; 0.1496; 0.2814; 0.2436; 0.2020; 0.2400 | — |
| SECONDARY Part A: Renal Clearance (CLr) of PF-07258669 |
0.06896; 0.05887; 0.1042; 0.09946; 0.08412; 0.08026 | — |
| SECONDARY Part B: Number of Participants With TEAEs |
2; 8; 2 | — |
| SECONDARY Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data |
0; 1; 1; 0; 1; 1 | — |
| SECONDARY Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria |
0; 0; 1 | — |
| SECONDARY Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality |
2; 4; 4 | — |
Eligibility Criteria
Inclusion Criteria
- For optional cohort of older adult participants only: Male participants and female participants of non childbearing potential must be 65 to 90 years of age, inclusive, at the time of signing the ICD (informed consent document). Attempts will be made to ensure that the age composition of this cohort (eg, approximately 70% of participants ≥70 years of age) is comparable to that of the anticipated patient population in later clinical studies.
- Female participants of nonchildbearing potential and male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
For optional cohort of older adult participants only: Participants must be in a stable condition at admission. These participants must be in reasonably good health as determined by the investigator based on a detailed medical history, full physical examination, vital signs assessments, 12-lead ECG (electrocardiogram), and clinical laboratory tests. Participants with mild, chronic, stable disease (eg, controlled hypertension, noninsulin dependent diabetes, osteoarthritis) may be enrolled if deemed medically prudent by the investigator.
- Participants who are willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure from admission to the follow-up contact and to apply sunscreen/lotion with a high sun protection factor and to wear eye protection, as appropriate.
- Body mass index (BMI) of 17.5 to 28.5 kg/m2; and a total body weight >50 kg (110 lb).
For optional cohort of older adult participants only: BMI of 17.5 to 32.4 kg/m2; and a total body weight >50 kg (110 lbs). Efforts will be made to enroll at least 3 older adult participants with BMI 2× ULN (upper limit of normal).
Data sourced from ClinicalTrials.gov (NCT05113940). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.