A Study of PF-07258669 In Healthy Adult Participants

NCT ID: NCT05113940

Last Updated: 2024-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-08
• Study Completion Date: 2023-07-27

Brief 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.

Conditions

Healthy Participants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

PF-07258669 and Placebo (Cohort 1)

Dose level 1: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: High Carbohydrate High Calorie (HCHC)

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 2)

Dose level 2: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: HCHC

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 3)

Dose level 3: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: HCHC

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 4)

Dose level 4: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: Standard Diet (SD)

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 5)

Dose level 5: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: SD

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 6)

Multiple dose administration of PF-07258669 and placebo over 14 days in Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: SD

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

Midazolam with and without PF-07258669 (Cohort 8)

Drug-drug interaction assessment of pharmacokinetics interaction in PF-07258669 and midazolam Dietary allocation: SD

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Midazolam

Intervention Type: DRUG

Single doses of Midazolam will be administered as oral solution alone and in combination with PF-07258669

PF-07258669 and Placebo (Cohort 7)

Multiple dose administration of PF-07258669 and placebo over 14 days in older adult participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: SD

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 9)

Dose level 6: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: SD

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 10)

Dose level 7: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: SD

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 11)

Dose level 8: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: SD

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 12)

Dose Level 9: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: High Fat High Calorie (HFHC)

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

PF-07258669 and Placebo (Cohort 13)

Dose Level 10: Multiple dose administration of PF-07258669 and placebo over 14 days in non-Japanese participants; 8 participants will receive PF-07258669 and 2 will receive placebo Dietary allocation: High Fat High Calorie (HFHC)

Group Type: EXPERIMENTAL

PF-07258669

Intervention Type: DRUG

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Placebo

Intervention Type: DRUG

Placebo will be administered as tablets; Q8H or Q12H over 14 days

Interventions

PF-07258669

PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days

Intervention Type: DRUG

Placebo

Placebo will be administered as tablets; Q8H or Q12H over 14 days

Intervention Type: DRUG

Midazolam

Single doses of Midazolam will be administered as oral solution alone and in combination with PF-07258669

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. 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.

4. 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 <25 kg/m2, if feasible.

5. Japanese participants only: Participants enrolling as Japanese must have 4 biological Japanese grandparents who were born in Japan.

Exclusion Criteria

1. Evidence or history of clinically significant hematological, renal, endocrine (including, but not limited to, thyroid disease, diabetes insipidus), pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including, but not limited to, primary polydipsia, obsessive compulsive disorder, anxiety disorder, schizophrenia), neurological (including, but not limited to, seizure disorder, traumatic brain injury), immunodeficiency (including, but not limited to, severe infection that required ICU admission, prolonged hospitalization, or prolonged treatment) or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing), as well as presence of clinical laboratory abnormalities.

For optional cohort of older adult participants only: Participants with chronic conditions (eg, hypertension) that are controlled by either diet or stable doses of medications may be included. Recent evidence (ie, within previous 6 months) or history of unstable disease or moderate to severe conditions which would, in the investigator's opinion, interfere with the study evaluations or have an impact on the safety of participants.

2. History of symptomatic orthostatic hypotension or symptomatic bradycardia.

3. History of eating disorders (eg, anorexia or bulimia nervosa, binge-eating disorder, avoidant/restrictive food intake disorder).

4. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.

For optional cohort of older adult participants only: Participants taking daily prescription or non-prescription medications (that are not moderate or strong cytochrome P450 (CYP3A) inducers or inhibitors) for management of acceptable chronic medical conditions are to be on a stable dose, as defined by no change in dose for the 28 days or 5 half-lives (whichever is longer) before the screening visit.

1. Use of stable concomitant mediations noted above that are CYP3A substrates may be restricted.

2. All medications must be reviewed on a case-by-case basis by the investigator and approved by the sponsor during the screening period for eligibility purposes.

5. Use of moderate or strong cytochrome P450 3A (CYP3A) inhibitors or inducers within 28 days or 5 half-lives (whichever is longer) prior to first dose of study intervention.

6. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).

7. Fasting serum triglycerides >2× ULN (upper limit of normal).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, Belgium

Countries

Belgium

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pmiform.com/clinical-trial-info-request?StudyID=C4541003

To obtain contact information for a study center near you, click here.

Other Identifiers

2021-004037-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C4541003

Identifier Type: -

Identifier Source: org_study_id