This study will be conducted in 2 parts. Part A will investigate the potential effect of PF-06865571 on the pharmacokinetics (PK) of PF-06882961 in healthy adult participants. Part B will evaluate the effect of PF-06882961 on the PK of PF-06865571, as well as the effect of PF-06865571 on the PK of PF-06882961 in overweight adults or adults with obesity who are otherwise healthy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
27
Treatment A - PF-06882961 20 mg single dose followed by Treatment B - PF-06882961 20 mg single dose plus PF-06865571 300 mg single dose. There will be a washout interval between periods of at least 3 days.
Treatment B - PF-06882961 20 mg single dose plus PF-06865571 300 mg single dose followed by Treatment A - PF-06882961 20 mg single dose. There will be a washout interval between periods of at least 3 days.
Period 1: PF-06865571 300 mg single dose (Day 1), Period 2: PF-06882961 10 mg twice daily dose titration up to 200 mg twice daily dosing (Days 3-46), Period 3: PF-06865571 300 mg single dose (Day 47) and PF-06882961 200 mg twice daily dosing (Days 47-48), Period 4: PF-06865571 300 mg twice daily dosing and PF-06882961 200 mg twice daily dosing (Days 49-62)
Orange County Research Center
Tustin, California, United States
Part A: PF-06882961 Maximum Observed Concentration (Cmax)
Cmax for PF-06882961 was observed directly from data.
Time frame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1
Part A: PF-06882961 Area Under the Plasma Concentration-time Profile From Time 0 to the Time 24 Hours Post-dose (AUC24)
AUC24 for PF-06882961 was determined by Linear/Log trapezoidal method.
Time frame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1
Part B: PF-06865571 Cmax on Day 1 and Day 47
Cmax for PF-06865571 was observed directly from data on Day 1 and Day 47.
Time frame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose
Part B: PF-06865571 Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) on Day 1 and Day 47
AUClast for PF-06865571 was determined by Linear/Log trapezoidal method on Day 1 and Day 47.
Time frame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose
Part B: PF-06865571 Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) on Day 1 and Day 47
AUCinf for PF-06865571 was calculated as AUClast + (Clast\*/kel) on Day 1 and Day 47. Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the elimination rate constant.
Time frame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose
Part B: PF-06882961 Cmax on Day 46 and Day 61
Cmax for PF-06882961 was observed directly from data on Day 46 and Day 61.
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Time frame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
Part B: PF-06882961 Area Under the Plasma Concentration-time Profile From Time 0 to the Time 12 Hours Post-dose (AUC12) on Day 46 and Day 61
AUC 12 for PF-06882961 was determined by Linear/Log trapezoidal method on Day 46 and Day 61.
Time frame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Part A
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any AEs occurring following start of study intervention were counted as treatment emergent. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Relatedness to study treatment was determined by the investigator.
Time frame: Up to 68 days
Number of Participants With Clinical Laboratory Abnormalities in Part A
Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion. Abnormalities without regard to baseline abnormalities were reported.
Time frame: From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria in Part A
Single, supine vital signs assessments included systolic blood pressure (BP), diastolic BP and pulse rate. Abnormality in vital signs included: pulse rate \<40 beats per minute (bpm) or \>120bpm; supine diastolic BP \<50 millimeter of mercury (mmHg), increase and decrease in change from baseline (BL) of \>=20mmHg; supine systolic blood pressure \<90mmHg, increase and decrease in change from BL of \>=30mmHg.
Time frame: From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria in Part A
ECG assessments included pulse rate (PR), QT, QTcF intervals and QRS complex. ECG abnormalities criteria included: PR interval value \>= 300msec, or baseline (BL) \>200msec and \>=25% increase from BL, or BL \<=200msec and \>=50% increase from BL; QRS interval value \>= 140msec, or percent change from BL \>=50%; QTcF value \>400 and \<=480msec, or \>480 and \<=500 msec, or \>500msec, or change from BL\>30 and \<=60msec, or change from BL \>60msec.
Time frame: From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days
Number of Participants With TEAEs in Part B
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any AEs occurring following start of study intervention were counted as treatment emergent. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Relatedness to study treatment was determined by the investigator.
Time frame: Up to 173 days
Number of Participants With Clinical Laboratory Abnormalities in Part B
Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion. Abnormalities without regard to baseline abnormalities were reported.
Time frame: From Screening (28 days prior to follow-up visit (up to 10 days after the last dose of treatment), for a maximum of 148 Days
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria in Part B
Single, supine vital signs assessments included systolic blood pressure (BP), diastolic BP and pulse rate. Abnormality in vital signs included: pulse rate \<40 beats per minute (bpm) or \>120bpm; supine diastolic BP \<50 millimeter of mercury (mmHg), increase and decrease in change from BL of \>=20mmHg; supine systolic blood pressure \<90mmHg, increase and decrease in change from BL of \>=30mmHg.
Time frame: From Screening (28 days prior to follow-up visit (up to 10 days after the last dose of treatment), for a maximum of 148 Days
Change From Baseline in Body Weight for Participants in Part B
Changes from baseline in body weight of the participants were measured.
Time frame: At Baseline (Days -28 to 2), on Period 2, Days 6, 13, 20 ,27, 34, and 41, Period 4, Days 9 and14 and follow-up visit (Days 68-71)
Number of Participants With ECG Data Meeting Pre-specified Criteria in Part B
ECG assessments included PR, QT, QTcF intervals and QRS complex. ECG abnormalities criteria included: PR interval value \>= 300msec, or BL \>200msec and \>=25% increase from BL, or BL \<=200msec and \>=50% increase from BL; QRS interval value \>= 140msec, or percent change from BL \>=50%; QTcF value \>400 and \<=480msec, or \>480 and \<=500 msec, or \>500msec, or change from BL\>30 and \<=60msec, or change from BL \>60msec.
Time frame: From Screening (28 days prior to follow-up visit (up to 10 days after the last dose of treatment), for a maximum of 148 Days
Number of Participants With Suicidal Ideation or Behavior as Per C-SSRS Mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) in Part B
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of "yes" on "actual attempt"), 3: preparatory acts toward imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts or behavior"), 4: any suicidal behavior or ideation, suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent"), 7: self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior").
Time frame: At Screening (Days -28 to -2), Baseline (Period 1 Day -1), on Period 2, Days 6, 13, 20, 27, 34 and 41, Period 4, Days 2, 9 and 14 and follow-up visit (Days 68-71)
Number of Participants With Response to PHQ-9 in Part B
The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The questions included "little interest/pleasure in things", "feeling down depressed or hopeless", "trouble falling or staying asleep", "feeling tired or little energy", "poor appetite or overeating", "feeling bad about yourself", "trouble concentrating on things", "moving slowly or fidgety/restless" and "thoughts you be better off dead". Each item was scored on scale of "not at all", "several days", "more than half the days" to "nearly every day". Total score range: 0-27 (each item with scale from 0 \[not at all\] to 3 \[nearly every day\]. Higher score=greater severity). Any participant with a response of any scale other than "not at all" to any of the 9 questions was counted.
Time frame: At Screening (Days -28 to -2), Baseline (Period 1 Day -1), on Period 2, Days 6, 13, 20, 27, 34 and 41, Period 4, Days 2, 9 and 14 and follow-up visit (Days 68-71)