A Study to Learn How Different Amounts of the Study Medicine Called PF-06954522 Are Tolerated and Act in the Body in Healthy Adults

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, CROSSOVER, FIRST-IN-HUMAN STUDY TO ASSESS THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE ASCENDING ORAL DOSES OF PF-06954522 IN HEALTHY ADULT PARTICIPANTS

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06003777

Enrollment

Registered

2023-08-22

Start date

2023-08-30

Completion date

2024-02-20

Last updated

2025-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Participants

Brief summary

The purposes of this study are: * To see how the new medicine (PF-06954522) under study behave. And if there are any important side effects. A side effect is a reaction (expected or unexpected) to a medicine or treatment you take. The study will see how people feel after taking single increasing amount of the medicine by mouth. * To measure the amount of study medicine in your blood after the medicine is taken by mouth. This study is seeking for participants who: * are females of 18 to 65 years old and are not able to give birth to a child. * are males of 18 to 65 years old. * have body mass index of 16 to 31 kilograms per meter squared. * have a total body weight of more than 50 kilograms (110 pounds). Participants will be chosen by chance, like drawing names out of a hat to receive either: * study medicine (PF-06954522) * or placebo (a pill that has no medicine in it). Participants may receive up to 4 amounts of study medicine and up to 2 amounts of placebo. The time frame of the study is approximately up to 36 days for each group and participants will stay at CRU for 20 days.

Interventions

DRUGPF-06954522

PF-06954522 will be administered as oral suspensions as escalating single doses to be determined.

DRUGPlacebo

Placebo will be administered as oral suspensions as escalating single doses to be determined.

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

1. Male and female participants of non-childbearing potential aged 18 to 65 years, inclusive, at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. 2. BMI of 16 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).

Exclusion criteria

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). 2. 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, with the exception of moderate or strong cytochrome P450 3A (CYP3A) inducers or inhibitors which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention. 3. Previous administration with an investigational product (drug or vaccine) 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). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study. 4. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results 5. Renal impairment as defined by an estimated glomerular filtration rate (eGFR) of \<75 mL/min/1.73 m². 6. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary: * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin * 1.05 × upper limit of normal (ULN); * TSH \> ULN; * HbA1c ≥6.5%; * Hematuria as defined by ≥1+ heme on urine dipstick; * Albuminuria as defined by urine albumin/creatinine ratio (UACR) \>30 mg/g.

Design outcomes

Primary

Measure	Time frame	Description
Cohort 3: Number of Participants According to Categorization of ECG Abnormalities Parameters	From Day 1 up to 35 days after last of study drug (maximum up to approximately 64 days)	Pre-specified ECG abnormalities criteria : PR interval millisecond (msec), value \>=300, baseline \> 200 and percentage (%) change \>=25%, baseline \<=200 and percentage change \>=50%; QRS duration (msec): value \>=140, % change\>= 50%; corrected QT interval using Fridericia's formula (QTcF) (msec): 450 \< value \<= 480, 480\<= value \<500, value \>=500, 30\<= change \<60 and change \> 60.
Cohort 2: Number of Participants With Clinical Chemistry Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 76 days)	Planned chemistry laboratory tests included: blood urea nitrogen, creatinine, cystatin C, estimated glomerular filtration rate, glucose (fasting), calcium, sodium, potassium. chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, alkaline phosphatase, creatine kinase, uric acid, albumin and total protein. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 3: Number of Participants With Clinical Chemistry Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 64 days)	Planned chemistry laboratory tests included: blood urea nitrogen, creatinine, cystatin C, estimated glomerular filtration rate, glucose (fasting), calcium, sodium, potassium. chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, alkaline phosphatase, creatine kinase, uric acid, albumin and total protein. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 1: Number of Participants With Urinalysis Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 88 days)	Planned urinalysis laboratory tests included: pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen and urine bilirubin. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 2: Number of Participants With Urinalysis Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 76 days)	Planned urinalysis laboratory tests included: pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen and urine bilirubin. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 3: Number of Participants With Urinalysis Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 64 days)	Planned urinalysis laboratory tests included: pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen and urine bilirubin. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 1: Number of Participants According to Categorization of Vital Signs Abnormalities Data	From Day 1 up to 35 days after last of study drug (maximum up to approximately 88 days)	Vital signs parameters were summarized according to pre-specified categorization of data: supine systolic blood pressure: Value less than (\<) 90 millimeter of mercury (mmHg), increase or decrease from baseline \>= 30mmHg, supine diastolic blood pressure: value \<50 mmHg, increase or decrease from baseline \>= 20mmHg and supine pulse rate: Value \< 40 beats per minute bpm or \> 120bpm.
Cohort 2: Number of Participants According to Categorization of Vital Signs Abnormalities Data	From Day 1 up to 35 days after last of study drug (maximum up to approximately 76 days)	Vital signs parameters were summarized according to pre-specified categorization of data: supine systolic blood pressure: Value less than (\<) 90 millimeter of mercury (mmHg), increase or decrease from baseline \>= 30mmHg, supine diastolic blood pressure: value \<50 mmHg, increase or decrease from baseline \>= 20mmHg and supine pulse rate: Value \< 40 beats per minute bpm or \> 120bpm.
Cohort 3: Number of Participants According to Categorization of Vital Signs Abnormalities Data	From Day 1 up to 35 days after last of study drug (maximum up to approximately 64 days)	Vital signs parameters were summarized according to pre-specified categorization of data: supine systolic blood pressure: Value less than (\<) 90 millimeter of mercury (mmHg), increase or decrease from baseline \>= 30mmHg, supine diastolic blood pressure: value \<50 mmHg and increase or decrease from baseline \>= 20mmHg.
Cohort 1: Number of Participants According to Categorization of Electrocardiogram (ECG) Abnormalities Parameters	From Day 1 up to 35 days after last of study drug (maximum up to approximately 88 days)	Pre-specified ECG abnormalities criteria : PR interval millisecond (msec), value \>=300, baseline \> 200 and percentage (%) change \>=25%, baseline \<=200 and percentage change \>=50%; QRS duration (msec): value \>=140, % change\>= 50%; corrected QT interval using Fridericia's formula (QTcF) (msec): 450 \< value \<= 480, 480\<= value \<500, value \>=500, 30\<= change \<60 and change \> 60.
Cohort 2: Number of Participants According to Categorization of ECG Abnormalities Parameters	From Day 1 up to 35 days after last of study drug (maximum up to approximately 76 days)	Pre-specified ECG abnormalities criteria : PR interval millisecond (msec), value \>=300, baseline \> 200 and percentage (%) change \>=25%, baseline \<=200 and percentage change \>=50%; QRS duration (msec): value \>=140, % change\>= 50%; corrected QT interval using Fridericia's formula (QTcF) (msec): 450 \< value \<= 480, 480\<= value \<500, value \>=500, 30\<= change \<60 and change \> 60.
Cohort 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 88 days)	An adverse event (AEs) 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that start on or after the first dose of study intervention, but before the end of the study were flagged as TEAEs. Serious AE (SAE) was defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect. AEs included SAEs and non-SAEs.
Cohort 2: Number of Participants With TEAEs	From Day 1 up to 35 days after last of study drug (maximum up to approximately 76 days)	An AEs 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that start on or after the first dose of study intervention, but before the end of the study were flagged as TEAEs. SAE was defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect. AEs included SAEs and non-SAEs.
Cohort 3: Number of Participants With TEAEs	From Day 1 up to 35 days after last of study drug (maximum up to approximately 64 days)	An AEs 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that start on or after the first dose of study intervention, but before the end of the study were flagged as TEAEs. SAE was defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect. AEs included SAEs and non-SAEs.
Cohort 1: Number of Participants With Hematology Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 88 days)	Planned hematology laboratory tests included: hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 2: Number of Participants With Hematology Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 76 days)	Planned hematology laboratory tests included: hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 3: Number of Participants With Hematology Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 64 days)	Planned hematology laboratory tests included: hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils and lymphocytes. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.
Cohort 1: Number of Participants With Clinical Chemistry Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	From Day 1 up to 35 days after last of study drug (maximum up to approximately 88 days)	Planned chemistry laboratory tests included: blood urea nitrogen, creatinine, cystatin C, estimated glomerular filtration rate, glucose (fasting), calcium, sodium, potassium. chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, alkaline phosphatase, creatine kinase, uric acid, albumin and total protein. The number of participants with results meeting pre-specified criteria (without regard to baseline abnormality) is reported.

Secondary

Measure	Time frame	Description
Cohort 2: AUClast of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	AUClast was determined by using linear/log trapezoidal method.
Cohort 1: Maximum Observed Concentration (Cmax) of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	Cmax of PF-06954522 was reported in this outcome measure.
Cohort 2: Cmax of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	Cmax of PF-06954522 was reported in this outcome measure.
Cohort 1: Time to Maximum Observed Concentration (Tmax) of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	Tmax of PF-06954522 was reported in this outcome measure.
Cohort 2: Tmax of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	Tmax of PF-06954522 was reported in this outcome measure.
Cohort 1: Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	Area under the plasma concentration-time profile from time 0 extrapolated to infinite time. It was determined by AUClast +(Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis.
Cohort 2: AUCinf of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	Area under the plasma concentration-time profile from time 0 extrapolated to infinite time. It was determined by AUClast +(Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis.
Cohort 1: Terminal Half-Life (t1/2) of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	t1/2 was determined by Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Cohort 2: t1/2 of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	t1/2was determined by Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Cohort 1: Area Under the Plasma Concentration-Time Profile From Time Zero (0) to Time of Last Quantifiable Concentration (AUClast) of PF-06954522	From 0 hours (pre-dose) to 72 hours following a single dose on Day 1	AUClast was determined by using linear/log trapezoidal method.

Countries

United States

Participant flow

Recruitment details

A total of 26 participants (initially randomized participants and replacement participants) were enrolled in this study. All participants received at least 1 dose of study intervention and were assigned in the study into 3 cohorts. As planned, there were replacement participants in the study who may or may not be required to complete all periods of the cohort in which they were participating at the discretion of the principal investigator and sponsor.

Pre-assignment details

In this study, dose have been reported from dose levels A to F, wherein Dose A is the lowest dose and Dose F is the highest dose received by study participants.

Participants by arm

Arm	Count
Cohort 1 Participants received up to 5 dose levels of PF-06954522 and matching placebo.	12
Cohort 2 Participants received up to 4 dose levels of PF-06954522 and matching placebo.	8
Cohort 3 Participants received up to 3 dose levels of PF-06954522 and matching placebo.	6
Total	26

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG004	FG006	FG008
Period 1	Adverse Event	0	1	0	0	0
Period 1	Withdrawal by Subject	0	0	1	0	0
Period 2	Withdrawal by Subject	0	0	0	0	1
Period 3	Adverse Event	0	0	0	1	0
Period 4	No longer met eligibility criteria	0	1	0	0	0
Period 4	Withdrawal by Subject	1	0	0	0	0

Baseline characteristics

Characteristic	Cohort 1	Cohort 2	Cohort 3	Total
Age, Continuous	43.6 Years STANDARD_DEVIATION 9.84	42.1 Years STANDARD_DEVIATION 11.44	42.5 Years STANDARD_DEVIATION 12.28	42.9 Years STANDARD_DEVIATION 10.48
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	5 Participants	0 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants	3 Participants	6 Participants	16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	6 Participants	7 Participants
Race (NIH/OMB) Black or African American	4 Participants	3 Participants	0 Participants	7 Participants
Race (NIH/OMB) More than one race	1 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	7 Participants	3 Participants	0 Participants	10 Participants
Sex: Female, Male Female	3 Participants	0 Participants	0 Participants	3 Participants
Sex: Female, Male Male	9 Participants	8 Participants	6 Participants	23 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk
deaths Total, all-cause mortality	0 / 11	0 / 4	0 / 7	0 / 8	0 / 8	0 / 8	0 / 6	0 / 2	0 / 6	0 / 6	0 / 4	0 / 5	0 / 4	0 / 2	0 / 4	0 / 4	0 / 3
other Total, other adverse events	3 / 11	1 / 4	5 / 7	8 / 8	6 / 8	8 / 8	6 / 6	0 / 2	2 / 6	2 / 6	0 / 4	5 / 5	3 / 4	2 / 2	4 / 4	4 / 4	3 / 3
serious Total, serious adverse events	0 / 11	0 / 4	0 / 7	0 / 8	0 / 8	0 / 8	0 / 6	0 / 2	0 / 6	0 / 6	0 / 4	0 / 5	0 / 4	0 / 2	0 / 4	0 / 4	0 / 3

Outcome results

Primary

Cohort 1: Number of Participants According to Categorization of Electrocardiogram (ECG) Abnormalities Parameters

Pre-specified ECG abnormalities criteria : PR interval millisecond (msec), value \>=300, baseline \> 200 and percentage (%) change \>=25%, baseline \<=200 and percentage change \>=50%; QRS duration (msec): value \>=140, % change\>= 50%; corrected QT interval using Fridericia's formula (QTcF) (msec): 450 \< value \<= 480, 480\<= value \<500, value \>=500, 30\<= change \<60 and change \> 60.

Time frame: From Day 1 up to 35 days after last of study drug (maximum up to approximately 88 days)