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
Overview
- Phase
- Phase 1
- Intervention
- PF-06954522
- Conditions
- Healthy Participants
- Sponsor
- Pfizer
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Cohort 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
- Status
- Completed
- Last Updated
- 10 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •BMI of 16 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
Exclusion Criteria
- •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).
- •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.
- •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.
- •Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
- •Renal impairment as defined by an estimated glomerular filtration rate (eGFR) of \<75 mL/min/1.73 m².
- •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%;
Arms & Interventions
Cohort 1
Single dose administration of PF-06954522 and placebo. Participants will receive up to 5 dose levels of PF-06954522 and up to 2 dose levels of matching placebo.
Intervention: PF-06954522
Cohort 1
Single dose administration of PF-06954522 and placebo. Participants will receive up to 5 dose levels of PF-06954522 and up to 2 dose levels of matching placebo.
Intervention: Placebo
Cohort 2
Single dose administration of PF-06954522 and placebo. Participants will receive up to 4 dose levels of PF-06954522 and up to 2 dose levels of matching placebo.
Intervention: PF-06954522
Cohort 2
Single dose administration of PF-06954522 and placebo. Participants will receive up to 4 dose levels of PF-06954522 and up to 2 dose levels of matching placebo.
Intervention: Placebo
Cohort 3
Single dose administration of PF-06954522 and placebo. Participants will receive up to 2 dose levels of PF-06954522 and up to 1 dose level of matching placebo.
Intervention: PF-06954522
Cohort 3
Single dose administration of PF-06954522 and placebo. Participants will receive up to 2 dose levels of PF-06954522 and up to 1 dose level of matching placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
Cohort 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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.
Cohort 2: Number of Participants With Clinical Chemistry Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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 3: Number of Participants According to Categorization of ECG Abnormalities Parameters
Time Frame: 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.
Secondary Outcomes
- Cohort 2: AUClast of PF-06954522(From 0 hours (pre-dose) to 72 hours following a single dose on Day 1)
- Cohort 1: Maximum Observed Concentration (Cmax) of PF-06954522(From 0 hours (pre-dose) to 72 hours following a single dose on Day 1)
- 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)
- Cohort 2: Tmax of PF-06954522(From 0 hours (pre-dose) to 72 hours following a single dose on Day 1)
- 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)
- Cohort 2: Cmax of PF-06954522(From 0 hours (pre-dose) to 72 hours following a single dose on Day 1)
- 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)
- Cohort 2: AUCinf of PF-06954522(From 0 hours (pre-dose) to 72 hours following a single dose on Day 1)
- 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)
- Cohort 2: t1/2 of PF-06954522(From 0 hours (pre-dose) to 72 hours following a single dose on Day 1)