Clinical trial NCT05113940: A Study of PF-07258669 In Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: PF-07258669
multiple dose
melanocortin-4 receptor
MC4R
healthy participants
safety
tolerability
pharmacokinetics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-11-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


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).

Primary outcomes:
measure: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days)
measure: Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
timeFrame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
measure: Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
timeFrame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
measure: Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
timeFrame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
measure: Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening
timeFrame: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
measure: Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2
timeFrame: Part A: On Day -2 (2 days prior to dosing)
measure: Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
timeFrame: Part A: On Day 7
measure: Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
timeFrame: Part A: Day 14
measure: Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21
timeFrame: Part A: Day 21
measure: Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening
timeFrame: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
measure: Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1
timeFrame: Part A: Day -1 (1 day prior to dosing)
measure: Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7
timeFrame: Part A: Day 7
measure: Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14
timeFrame: Part A: Day 14
measure: Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone on Day 1 of Period 1
timeFrame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
measure: Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
timeFrame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
measure: Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
timeFrame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
measure: 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
timeFrame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
measure: Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
timeFrame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
measure: Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
timeFrame: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
measure: 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
timeFrame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
measure: Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
timeFrame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
measure: Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
timeFrame: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
Secondary outcomes:
measure: Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14
timeFrame: Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14
measure: Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14
timeFrame: Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14
measure: 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
timeFrame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
measure: 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
timeFrame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
measure: Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14
timeFrame: Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14
measure: Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
timeFrame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
measure: Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
timeFrame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
measure: Part A: Renal Clearance (CLr) of PF-07258669
timeFrame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
measure: Part B: Number of Participants With TEAEs
timeFrame: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)
measure: Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
timeFrame: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
measure: Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
timeFrame: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
measure: Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
timeFrame: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: