Healthy ParticipantsPhase 1NCT05113940

A Study of PF-07258669 In Healthy Adult Participants

A Phase 1 study testing PF-07258669 and Midazolam in people with Healthy Participants, run by Pfizer at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Participants
What is being tested?: PF-07258669 and Midazolam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 120 participants
Where: 1 siteBelgium
Study dates: 8 Nov 2021to 27 Jul 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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 <25 kg/m2, if feasible.
Japanese participants only: Participants enrolling as Japanese must have 4 biological Japanese grandparents who were born in Japan.

Who cannot join

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

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Use of stable concomitant mediations noted above that are CYP3A substrates may be restricted.
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.
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.
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).
Fasting serum triglycerides >2× ULN (upper limit of normal).

Trial locations and contacts

1 site in 1 country.

Belgium1 site

Pfizer Clinical Research Unit - Brussels
Brussels, Bruxelles-capitale, Région de, B-1070

Other trials in Belgium

About this study

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

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
Being tested: PF-07258669, Placebo, Midazolam
Keywords: PF-07258669, multiple dose, melanocortin-4 receptor, MC4R, healthy participants, safety, tolerability, pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT05113940
Study group	Role	What they receive
PF-07258669 and Placebo (Cohort 1)	Experimental	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) Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 2)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 3)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 4)	Experimental	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) Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 5)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 6)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
Midazolam with and without PF-07258669 (Cohort 8)	Experimental	Drug-drug interaction assessment of pharmacokinetics interaction in PF-07258669 and midazolam Dietary allocation: SD Receives: Drug: PF-07258669; Drug: Midazolam
PF-07258669 and Placebo (Cohort 7)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 9)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 10)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 11)	Experimental	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 Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 12)	Experimental	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) Receives: Drug: PF-07258669; Drug: Placebo
PF-07258669 and Placebo (Cohort 13)	Experimental	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) Receives: Drug: PF-07258669; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study intervention and up to 35 days after last dose of study intervention that were absent before treatment or that worsened after treatment.
Measured: Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days)
Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
Laboratory assessments included clinical chemistry, hematology, and urinalysis. Abnormality was determined based on the criteria specified in the sponsor reporting standards. The primary criteria was less than (<) 0.8* lower limit of normal (LLN) for lymphocytes and lymphocytes/leukocytes, greater than (>) 1.2* upper limit of normal (ULN) for lymphocytes, eosinophils/leukocytes, monocytes, and monocytes/leukocytes; greater than (>) 3.0* ULN for alanine aminotransferase, >1.3* ULN for urea nitrogen, cholesterol, and triglycerides; >1.030 for specific gravity (scalar), greater than or equal to (>=) 1 for ketones, urine protein, urine hemoglobin, urine bilirubin, leukocyte esterase.
Measured: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
Vital signs included: a) supine systolic blood pressure (SBP): change greater than or equal to (>=) 30 millimeters of mercury (mmHg) increase, postural difference (supine standing) >= 20 mmHg, standing systolic SBP (mmHg) less than (<) 90 mmHg, >= 160 mmHg, change >= 30 mmHg increase, change >= 30 mmHg decrease; b) supine diastolic blood pressure (DBP) < 50 mmHg, >= 90 mmHg, change >= 20 mmHg increase, change >= 20mmHg decrease; postural difference (supine standing) >= 10 mmHg; standing <50 mmHg, value >=90 mmHg, change >=20 mmHg increase, change >=20 mmHg decrease, C) standing pulse rate (PR) greater than (>) 140 bpm. Baseline for supine BP and pulse rate was defined as the average of the triplicate measurements collected at the pre-dose (0 hour) assessment on Day 1. Baseline for standing BP, standing pulse rate, respiratory rate and oral body temperature were defined as the pre-dose (0 hour) assessment on Day 1.
Measured: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
ECG criteria: QTc corrected using Fridericia's formula (QTCF) interval aggregate in milliseconds (msec): less than or equal to (<=) change <= 60 msec. Baseline was defined as the average of the triplicate ECG measurements over the 3 pre-dose measurement times (-1 hour, -0.5 hour, and pre-dose 0 hour; total of 9 ECG measurements) on Day 1.
Measured: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Measured: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Measured: Part A: On Day -2 (2 days prior to dosing)
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Measured: Part A: On Day 7
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Measured: Part A: Day 14
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Measured: Part A: Day 21
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by clinical research unit (CRU) staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Measured: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Measured: Part A: Day -1 (1 day prior to dosing)
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Measured: Part A: Day 7
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Measured: Part A: Day 14
Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone on Day 1 of Period 1
Cmax was defined as the maximum observed plasma concentration.
Measured: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
Cmax is the maximum observed plasma concentration.
Measured: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
Cmax was defined as the maximum observed plasma concentration.
Measured: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
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
AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Measured: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Measured: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Measured: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
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
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Measured: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Measured: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Measured: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10

Secondary outcomes (12)

Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14
Cmax was defined as the maximum plasma concentration.
Measured: 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
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14
Cmax was defined maximum observed serum concentration. Cmax (dn) was calculated as Cmax/dose.
Measured: 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
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
Area under the plasma concentration-time profile from time zero to time tau, the dosing interval, where tau = 8 hours.
Measured: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
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
Measured: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14
Tmax was defined as the time taken (in hours) to reach the maximum plasma drug concentration.
Measured: 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
Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Aetau was defined as the amount of unchanged drug recovered in urine during the dosing interval.
Measured: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
Aetau% was defined as the percentage of dose recovered in urine as unchanged drug.
Measured: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Part A: Renal Clearance (CLr) of PF-07258669
Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).
Measured: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Part B: Number of Participants With TEAEs
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment.
Measured: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)
Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
Vital signs examination included: supine systolic blood pressure with criteria change >= 30 mmHg decrease, supine diastolic blood pressure with criteria value >= 90 mmHg and change >= 20 mmHg decrease.
Measured: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
Following ECG parameters were analyzed: QTCF interval with criteria 450 less than (<) value less than or equal to (<=) 480. A standard 12-lead ECGs utilizing limb leads were collected using an ECG machine that automatically calculated the heart rate and measures PR, QT, and QTc intervals and QRS complex. On Day 1 at -1 hour (h), -0.5h, and 0h prior to the morning dose, triplicate 12-lead ECGs were obtained approximately 2 to 4 minutes apart at each time point. The average of the triplicate ECG measurements over the 3 pre dose measurement times (total of 9 ECG measurements) collected before morning dose administration on Day 1 served as each participant's baseline QTc value.
Measured: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
Laboratory parameters assessed included: hematology (monocytes, monocytes/leukocytes) with primary criteria greater than (>) 1.2*upper limit of normal (ULN), clinical chemistry (bilirubin, direct bilirubin and indirect bilirubin with primary criteria >1.5*ULN, alanine aminotransferase with primary criteria >3.0*ULN, creatine kinase with primary criteria >2.0*ULN, urobilinogen with primary criteria greater than or equal to (>=)1, cholesterol and triglycerides-fasting with primary criteria >1.3*ULN), urinalysis (ketones and urine hemoglobin with primary criteria >=1).
Measured: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Nov 202127 Jul 2023

First posted9 Nov 2021
Study start8 Nov 2021
Primary completion27 Jul 2023
Study completion27 Jul 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 120 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05113940
Sponsor's protocol ID: C4541003
Other IDs: 2021-004037-36
Status last verified: Jul 2024
First submitted: 13 Oct 2021
Last updated: 24 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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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Study at a glance

From the registry record, last updated by the sponsor on 24 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05113940
Acronym / sponsor ID: C4541003
Conditions: Healthy Participants
Keywords: PF-07258669, multiple dose, melanocortin-4 receptor, MC4R, healthy participants, safety, tolerability, pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 120 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 8 Nov 2021 (actual)
Primary completion: 27 Jul 2023 (actual)
Study completion: 27 Jul 2023 (actual)
First posted: 9 Nov 2021 (actual)
Results: Posted 24 Oct 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 13

Arm	Type	Receives
PF-07258669 and Placebo (Cohort 1)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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)
PF-07258669 and Placebo (Cohort 2)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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
PF-07258669 and Placebo (Cohort 3)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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
PF-07258669 and Placebo (Cohort 4)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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)
PF-07258669 and Placebo (Cohort 5)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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
PF-07258669 and Placebo (Cohort 6)	Experimental	Drug: PF-07258669, Drug: PlaceboMultiple 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
Midazolam with and without PF-07258669 (Cohort 8)	Experimental	Drug: PF-07258669, Drug: MidazolamDrug-drug interaction assessment of pharmacokinetics interaction in PF-07258669 and midazolam Dietary allocation: SD
PF-07258669 and Placebo (Cohort 7)	Experimental	Drug: PF-07258669, Drug: PlaceboMultiple 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
PF-07258669 and Placebo (Cohort 9)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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
PF-07258669 and Placebo (Cohort 10)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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
PF-07258669 and Placebo (Cohort 11)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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
PF-07258669 and Placebo (Cohort 12)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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)
PF-07258669 and Placebo (Cohort 13)	Experimental	Drug: PF-07258669, Drug: PlaceboDose 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)

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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).

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PF-07258669PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days	Drug	Midazolam with and without PF-07258669 (Cohort 8), PF-07258669 and Placebo (Cohort 1), PF-07258669 and Placebo (Cohort 10), PF-07258669 and Placebo (Cohort 11), PF-07258669 and Placebo (Cohort 12), PF-07258669 and Placebo (Cohort 13), PF-07258669 and Placebo (Cohort 2), PF-07258669 and Placebo (Cohort 3), PF-07258669 and Placebo (Cohort 4), PF-07258669 and Placebo (Cohort 5), PF-07258669 and Placebo (Cohort 6), PF-07258669 and Placebo (Cohort 7), PF-07258669 and Placebo (Cohort 9)
PlaceboPlacebo will be administered as tablets; Q8H or Q12H over 14 days	Drug	PF-07258669 and Placebo (Cohort 1), PF-07258669 and Placebo (Cohort 10), PF-07258669 and Placebo (Cohort 11), PF-07258669 and Placebo (Cohort 12), PF-07258669 and Placebo (Cohort 13), PF-07258669 and Placebo (Cohort 2), PF-07258669 and Placebo (Cohort 3), PF-07258669 and Placebo (Cohort 4), PF-07258669 and Placebo (Cohort 5), PF-07258669 and Placebo (Cohort 6), PF-07258669 and Placebo (Cohort 7), PF-07258669 and Placebo (Cohort 9)
MidazolamSingle doses of Midazolam will be administered as oral solution alone and in combination with PF-07258669	Drug	Midazolam with and without PF-07258669 (Cohort 8)

Primary outcome

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study intervention and up to 35 days after last dose of study intervention that were absent before treatment or that worsened after treatment.
Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Laboratory assessments included clinical chemistry, hematology, and urinalysis. Abnormality was determined based on the criteria specified in the sponsor reporting standards. The primary criteria was less than (<) 0.8* lower limit of normal (LLN) for lymphocytes and lymphocytes/leukocytes, greater than (>) 1.2* upper limit of normal (ULN) for lymphocytes, eosinophils/leukocytes, monocytes, and monocytes/leukocytes; greater than (>) 3.0* ULN for alanine aminotransferase, >1.3* ULN for urea nitrogen, cholesterol, and triglycerides; >1.030 for specific gravity (scalar), greater than or equal to (>=) 1 for ketones, urine protein, urine hemoglobin, urine bilirubin, leukocyte esterase.
Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Vital signs included: a) supine systolic blood pressure (SBP): change greater than or equal to (>=) 30 millimeters of mercury (mmHg) increase, postural difference (supine standing) >= 20 mmHg, standing systolic SBP (mmHg) less than (<) 90 mmHg, >= 160 mmHg, change >= 30 mmHg increase, change >= 30 mmHg decrease; b) supine diastolic blood pressure (DBP) < 50 mmHg, >= 90 mmHg, change >= 20 mmHg increase, change >= 20mmHg decrease; postural difference (supine standing) >= 10 mmHg; standing <50 mmHg, value >=90 mmHg, change >=20 mmHg increase, change >=20 mmHg decrease, C) standing pulse rate (PR) greater than (>) 140 bpm. Baseline for supine BP and pulse rate was defined as the average of the triplicate measurements collected at the pre-dose (0 hour) assessment on Day 1. Baseline for standing BP, standing pulse rate, respiratory rate and oral body temperature were defined as the pre-dose (0 hour) assessment on Day 1.
Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
ECG criteria: QTc corrected using Fridericia's formula (QTCF) interval aggregate in milliseconds (msec): less than or equal to (<=) change <= 60 msec. Baseline was defined as the average of the triplicate ECG measurements over the 3 pre-dose measurement times (-1 hour, -0.5 hour, and pre-dose 0 hour; total of 9 ECG measurements) on Day 1.
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening
Time frame: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2
Time frame: Part A: On Day -2 (2 days prior to dosing)
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
Time frame: Part A: On Day 7
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
Time frame: Part A: Day 14
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21
Time frame: Part A: Day 21
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response "Yes" to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response "Yes" on "Completed Suicide",2.Suicide attempt had response "Yes" on "Actual Attempt",3.Interrupted attempt, had response "Yes" on "Interrupted attempt",4.Aborted attempt, had response "Yes" on "Aborted attempt",5.Preparatory actions toward imminent suicidal behaviors, had response "Yes" on "Preparatory Acts or Behavior".Here, number of participants with positive response (response of "yes") to suicidal behavior or ideation were reported.
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening
Time frame: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by clinical research unit (CRU) staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1
Time frame: Part A: Day -1 (1 day prior to dosing)
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7
Time frame: Part A: Day 7
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14
Time frame: Part A: Day 14
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone on Day 1 of Period 1
Time frame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
Cmax was defined as the maximum observed plasma concentration.
Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
Cmax is the maximum observed plasma concentration.
Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
Cmax was defined as the maximum observed plasma concentration.
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
Time frame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
Time frame: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
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
Time frame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
Time frame: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.

12 secondary outcomes

Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14
Time frame: 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
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14
Time frame: 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
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
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
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
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14
Time frame: 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
Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Part A: Renal Clearance (CLr) of PF-07258669
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Part B: Number of Participants With TEAEs
Time frame: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)
Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
Time frame: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
Time frame: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
Time frame: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)

Results and safety

Results posted to the registry on 24 Oct 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo: 18-60 Years (HC-HC Diet)	6	6
PF-07258669 2 mg: 18-60 Years (HC-HC Diet)	8	8
PF-07258669 3 mg: 18-60 Years (HC-HC Diet)	8	7
PF-07258669 6 mg: 18-60 Years (HC-HC Diet)	7	6
Placebo: 18-60 Years (Standard Diet)	10	9
PF-07258669 6 mg: 18-60 Years (Standard Diet)	8	8
PF-07258669 20 mg: 18-60 Years (Standard Diet)	8	8
PF-07258669 60 mg: 18-60 Years (Standard Diet)	8	8
PF-07258669 125 mg: 18-60 Years (Standard Diet)	8	8
PF-07258669 180 mg: 18-60 Years (Standard Diet)	8	8
Placebo: 18-60 Years (HF-HC Diet)	12	12
PF-07258669 180 mg: 18-60 Years (HF-HC Diet)	12	10
Placebo: Japanese 18-60 Years (Standard Diet)	1	1
PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet)	5	5
Midazolam Then PF-07258669 + Midazolam: Standard Diet	0	0

Primary outcome: Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Time frame: Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days). Count of participants. Unit: Participants

Measure	Placebo: 18-60 Years (HC-HC Diet) n = 6	PF-07258669 2 mg: 18-60 Years (HC-HC Diet) n = 8	PF-07258669 3 mg: 18-60 Years (HC-HC Diet) n = 8	PF-07258669 6 mg: 18-60 Years (HC-HC Diet) n = 7	Placebo: 18-60 Years (Standard Diet) n = 10	PF-07258669 6 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 20 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 60 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 125 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 180 mg: 18-60 Years (Standard Diet) n = 8	Placebo: 18-60 Years (HF-HC Diet) n = 12	PF-07258669 180 mg: 18-60 Years (HF-HC Diet) n = 12	Placebo: Japanese 18-60 Years (Standard Diet) n = 1	PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) n = 5
Value	5	8	6	6	9	6	7	4	7	8	8	10	0	3

Population analysed: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.

Primary outcome: Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality

Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days). Count of participants. Unit: Participants

Measure	Placebo: 18-60 Years (HC-HC Diet) n = 6	PF-07258669 2 mg: 18-60 Years (HC-HC Diet) n = 8	PF-07258669 3 mg: 18-60 Years (HC-HC Diet) n = 8	PF-07258669 6 mg: 18-60 Years (HC-HC Diet) n = 7	Placebo: 18-60 Years (Standard Diet) n = 10	PF-07258669 6 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 20 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 60 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 125 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 180 mg: 18-60 Years (Standard Diet) n = 8	Placebo: 18-60 Years (HF-HC Diet) n = 12	PF-07258669 180 mg: 18-60 Years (HF-HC Diet) n = 12	Placebo: Japanese 18-60 Years (Standard Diet) n = 1	PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) n = 5
Value	5	6	6	6	9	5	8	7	8	4	11	8	1	3

Population analysed: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.

Primary outcome: Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data

Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days). Count of participants. Unit: Participants

Measure	PF-07258669 3 mg: 18-60 Years (HC-HC Diet) n = 8	PF-07258669 6 mg: 18-60 Years (HC-HC Diet) n = 7	Placebo: 18-60 Years (Standard Diet) n = 10	PF-07258669 6 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 20 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 60 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 125 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 180 mg: 18-60 Years (Standard Diet) n = 8	Placebo: 18-60 Years (HF-HC Diet) n = 12	PF-07258669 180 mg: 18-60 Years (HF-HC Diet) n = 12	Placebo: Japanese 18-60 Years (Standard Diet) n = 1	PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) n = 5
Supine SBP Change >= 30mmHg increase	1	0	1	0	0	0	0	0	0	0	0	0
SBP postural difference >=20mmHg	0	0	1	0	1	1	0	0	0	0	0	0
Standing SBP Value < 90 mmHg	0	0	0	0	0	1	1	0	0	1	0	0
Standing SBP Value >= 160 mmHg

Primary outcome: Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria

Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days). Count of participants. Unit: Participants

Measure	Placebo: 18-60 Years (HC-HC Diet) n = 6	PF-07258669 2 mg: 18-60 Years (HC-HC Diet) n = 8	PF-07258669 3 mg: 18-60 Years (HC-HC Diet) n = 8	PF-07258669 6 mg: 18-60 Years (HC-HC Diet) n = 7	Placebo: 18-60 Years (Standard Diet) n = 10	PF-07258669 6 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 20 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 60 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 125 mg: 18-60 Years (Standard Diet) n = 8	PF-07258669 180 mg: 18-60 Years (Standard Diet) n = 8	Placebo: 18-60 Years (HF-HC Diet) n = 12	PF-07258669 180 mg: 18-60 Years (HF-HC Diet) n = 12	Placebo: Japanese 18-60 Years (Standard Diet) n = 1	PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) n = 5
Value	0	1	0	0	0	0	0	0	1	1	0	1	0	0

Population analysed: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days), 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 adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo: 18-60 Years (HC-HC Diet)	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
PF-07258669 2 mg: 18-60 Years (HC-HC Diet)	0 of 8 (0%)	8 of 8 (100%)	0 of 8
PF-07258669 3 mg: 18-60 Years (HC-HC Diet)	1 of 8 (12.5%)	6 of 8 (75%)	0 of 8
PF-07258669 6 mg: 18-60 Years (HC-HC Diet)	0 of 7 (0%)	6 of 7 (85.7%)	0 of 7
Placebo: 18-60 Years (Standard Diet)	0 of 10 (0%)	9 of 10 (90%)	0 of 10
PF-07258669 6 mg: 18-60 Years (Standard Diet)	0 of 8 (0%)	6 of 8 (75%)	0 of 8
PF-07258669 20 mg: 18-60 Years (Standard Diet)	0 of 8 (0%)	7 of 8 (87.5%)	0 of 8
PF-07258669 60 mg: 18-60 Years (Standard Diet)	0 of 8 (0%)	4 of 8 (50%)	0 of 8
PF-07258669 125 mg: 18-60 Years (Standard Diet)	0 of 8 (0%)	7 of 8 (87.5%)	0 of 8
PF-07258669 180 mg: 18-60 Years (Standard Diet)	0 of 8 (0%)	8 of 8 (100%)	0 of 8
Placebo: 18-60 Years (HF-HC Diet)	0 of 12 (0%)	8 of 12 (66.7%)	0 of 12
PF-07258669 180 mg: 18-60 Years (HF-HC Diet)	0 of 12 (0%)	10 of 12 (83.3%)	0 of 12
Placebo: Japanese 18-60 Years (Standard Diet)	0 of 1 (0%)	0 of 1 (0%)	0 of 1
PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet)	0 of 5 (0%)	3 of 5 (60%)	0 of 5
Part B Period 1: Midazolam	0 of 11 (0%)	2 of 11 (18.2%)	0 of 11
Part B Period 2: PF-07258669 + Midazolam (Day 2)	0 of 11 (0%)	8 of 11 (72.7%)	0 of 11

Limitations and caveats (from the sponsor): Any untoward findings identified on physical and/or neurological examinations, cardiac monitoring and pulse oximeter monitoring conducted during the active collection period were captured as adverse events, if those findings met the definition of an AE.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-07258669 and Midazolam in people with Healthy Participants, run by Pfizer at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (time frame: Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days)). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05113940.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2024.