A Study of PF-07258669 In Healthy Adult Participants

Healthy Participants Clinical Trial

Official title:

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACOKINETIC INTERACTION WITH MIDAZOLAM OF MULTIPLE ASCENDING ORAL DOSES OF PF-07258669 IN HEALTHY NON-JAPANESE AND JAPANESE ADULT PARTICIPANTS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05113940
• Other study ID #: C4541003
• Secondary ID: 2021-004037-36
• Status: Completed
• Phase: Phase 1
• Start date: November 8, 2021
• Est. completion date: July 27, 2023

Study information

• Verified date: August 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 27, 2023
• Est. primary completion date: July 27, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• PF-07258669
PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days
• Placebo
Placebo will be administered as tablets; Q8H or Q12H over 14 days
• Midazolam
Single doses of Midazolam will be administered as oral solution alone and in combination with PF-07258669

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit - Brussels	Brussels	Bruxelles-capitale, Région DE

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	Part A: Number of Participants With Clinical Laboratory Abnormalities		Baseline up to 10 days after last dose of study intervention (approximately 7 weeks).
Primary	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).
Primary	Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry		0 to 8 hours post-dose on Day 1
Primary	Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry		0 to 8 hours post-dose on Day 7
Primary	Part A: Number of Participants With Cardiac Rhythms of Potential Clinical Concern Assessed By Telemetry		0 to 8 hours post-dose on Day 14
Primary	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).
Primary	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).
Primary	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).
Primary	Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14	C-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide; suicide attempt (response of "Yes" on "actual attempt"); preparatory acts toward imminent suicidal behavior ("Yes" on "preparatory acts or behavior", "aborted attempt" or "interrupted attempt"), suicidal ideation ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent). In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation or any self-injurious behavior, at Day 14 were reported.	Day 14
Primary	Part A: Number of Participants With Clinically Significant Change From Baseline in 24-Hour Fluid Intake		0 to 24 hours on Day -1
Primary	Part A: Number of Participants With Clinically Significant Change From Baseline in 24-Hour Fluid Intake		0 to 24 hours on Day 7
Primary	Part A: Number of Participants With Clinically Significant Change From Baseline in 24-Hour Fluid Intake		0 to 24 hours on Day 14
Primary	Part A: Number of Participants With Clinically Significant Change From Baseline in 24-Hour Urine Output		0 to 24 hours on Day -1
Primary	Part A: Number of Participants With Clinically Significant Change From Baseline in 24-Hour Urine Output		0 to 24 hours on Day 7
Primary	Part A: Number of Participants With Clinically Significant Change From Baseline in 24-Hour Urine Output		0 to 24 hours on Day 14
Primary	Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam		Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose on Period 1/Day 1
Primary	Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam		Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose on Period 2/Day 2
Primary	Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam		Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose on Period 2/Day10
Primary	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, 12, 16 and 24 hours post dose on Period 1/Day 1
Primary	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, 12, 16 and 24 hours post dose on Period 2/Day 2
Primary	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, 12, 16 and 24 hours post dose on Period 2/Day10
Primary	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, 12, 16 and 24 hours post dose on Period 1/Day 1
Primary	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, 12, 16 and 24 hours post dose on Period 2/Day 2
Primary	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, 12, 16 and 24 hours post dose on Period 2/Day10
Secondary	Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 1
Secondary	Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 14
Secondary	Part A: Dose Normalized Maximum Observed Plasma Concentration (Dose-Normalized Cmax) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 1
Secondary	Part A: Dose Normalized Maximum Observed Plasma Concentration (Dose-Normalized Cmax) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 14
Secondary	Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (tau) (AUCtau) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 1
Secondary	Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (tau) (AUCtau) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 14
Secondary	Part A: Dose Normalized Area Under the Curve from Time 0 to Dosing Interval (tau) (Dose-Normalized AUCtau) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 1
Secondary	Part A: Dose Normalized Area Under the Curve from Time 0 to Dosing Interval (tau) (Dose-Normalized AUCtau) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 14
Secondary	Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 1
Secondary	Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669		Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post dose on Day 14
Secondary	Part A: Amount of PF-0728669 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, 0-8 hours for 8 hour dosing interval; 0-12 hours for 12 hour dosing interval)
Secondary	Part A: Percentage of Dose of PF-07258669 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, 0-8 hours for 8 hour dosing interval; 0-12 hours for 12 hour dosing interval)
Secondary	Part A: Renal Clearance of PF-07258669		On Day 14, urine collection for PK to occur over 0-tau, according to dosing frequency (ie, 0-8 hours for 8 hour dosing interval; 0-12 hours for 12 hour dosing interval)
Secondary	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)
Secondary	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)
Secondary	Part B: Number of Participants With Oxygen Saturation Levels of Potential Clinical Concern		0 to 6 hours post-dose on Period 1/Day 1
Secondary	Part B: Number of Participants With Oxygen Saturation Levels of Potential Clinical Concern		0 to 6 hours post-dose on Period 2/Day 2
Secondary	Part B: Number of Participants With Oxygen Saturation Levels of Potential Clinical Concern		0 to 6 hours post-dose on Period 2/Day 10
Secondary	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)
Secondary	Part B: Number of Participants With Clinical Laboratory Abnormalities		Baseline up to 10 days after last dose of study intervention (approximately 7 weeks)
Secondary	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)

External Links

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