Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a Phase 1, randomized, double blind (sponsor open), parallel, placebo controlled, twice daily oral dosing study of PF 06882961 in adult Japanese participants with T2DM inadequately controlled on diet and exercise alone.
Interventions
DRUGPlacebo
3 matching placebo tablets taken twice a day (BID)
DRUGPF-06882961
Participants will be randomized to one of 3 active doses (40, 80, or 120 mg), taking 3 tablets twice daily for 8 weeks.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with T2DM who are treated with diet and exercise * HbA1c greater than or equal to 7% and less than or equal to 10.5% * Total body weight \>50 kg (110 lb) with BMI 22.5 to 45.4 kg/m\^2
Exclusion criteria
* Any condition possibly affecting drug absorption * Diagnosis of Type 1 diabetes * History of myocardial infarction, unstable angina, arterial revascularization, stroke, heart failure, or transient ischemic attack within 6 months of screening * Any malignancy not considered cured * Personal or family history of MTC or MEN2, or participants with suspected MTC * Acute pancreatitis or history of chronic pancreatitis * Symptomatic gallbladder disease * Known medical history of active proliferative retinopathy and/or macular edema * Known history of HIV, hepatitis B, hepatitis C or syphilis * Supine blood pressure greater than or equal to 160 mmHg (systolic) or greater than or equal to 100 mmHg (diastolic) * Clinically relevant ECG abnormalities * Positive urine drug test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline (1 Day before dosing) up to last dose (maximum up to Week 8) | PR interval had following categories: maximum absolute PR interval \>=300 milliseconds (msec); when baseline PR interval \>200 msec and maximum increase from baseline in PR interval \>=25 percent; when baseline PR interval less than or equal to (\<=) 200 msec and maximum increase from baseline in PR interval \>=50 percent. QRS interval had following categories: maximum absolute QRS interval \>=140 msec; maximum increase from baseline in QRS interval \>=50 percent. QTC interval with Frederica's correction (QTCF) had following categories: absolute QTCF interval \>450 msec to \<=480 msec; absolute QTCF interval \>480 msec to \<=500 msec; absolute QTCF interval \>500 msec; QTCF interval increase from baseline \>=30 msec to \<=60 msec; QTCF interval increase from baseline \>60 msec. |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks) | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. Treatment emergent AEs were events between first dose of study drug and approximately 4 weeks after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs. |
| Number of Participants With Clinical Laboratory Abnormalities | Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks) | Leukocytes (10\^9/liter \[L\]) bilirubin (micromol/L), glucose (millimoles \[mmol\]/L), triacylglycerol lipase (microkatals \[microkat\]/L): greater than (\>) 1.5\*upper limit normal (ULN); activated partial thromboplastin time (s): 1.1\*ULN; HDL cholesterol (mmol/L), thyroid stimulating hormone (TSH) (milliunits \[mU\]/L): less than (\<) 0.8\*lower limit normal (LLN); LDL cholesterol (mmol/L), urate (mmol/L): \>1.2\*ULN; triglycerides: \>1.3\*ULN; aspartate aminotransferase (microkat/L), alanine aminotransferase (microkat/L), gamma glutamyl transferase (microkat/L): \>3.0\*ULN; cholesterol (mmol/L): \>1.3\*ULN; urine glucose, ketones urine protein, urine hemoglobin, urobilinogen, nitrite, leukocyte esterase: greater than or equal to (\>=) 1; granular casts, hyaline casts: \>1. |
| Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Baseline (1 Day before dosing) up to last dose (maximum up to Week 8) | Supine systolic blood pressure (SBP) measured in millimeter of mercury (mmHg) had following categories: minimum of absolute SBP \<90 mmHg, maximum of SBP \>=30 mmHg decrease from baseline and maximum of SBP \>=30 mmHg increase from baseline. Supine diastolic blood pressure (DBP) measured in mmHg had following categories: minimum of absolute DBP \<50 mmHg, maximum of DBP \>20 mmHg decrease from baseline and maximum of DBP \>=20 mmHg increase from baseline. Supine pulse rate measured in beats per minute (BPM) had following categories: minimum of absolute supine pulse rate \<40 BPM and maximum of absolute supine pulse rate \>120 BPM. Baseline was defined as the time-matched value from the average of the triplicate recordings on Day -1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1 and 56 | AUC24= Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24). |
| Maximum Plasma Concentration (Cmax) Observed of PF-06882961 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56 | — |
| Terminal Phase Half-Life (t1/2) of PF-06882961 | Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56 | t1/2 was calculated as loge (2) per kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
Countries
Japan
Participant flow
Pre-assignment details
65 participants signed the inform consent form (ICF). 28 participants were screen failures who did not meet criteria and were not enrolled. 37 participants enrolled into the study and assigned to a study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants with T2DM were randomized to receive placebo matched to PF-06882961 tablet twice daily, for 8 weeks. Post treatment participants were followed approximately for 4 weeks. | 9 |
| PF-06882961 40 mg Participants with T2DM were randomized to receive PF-06882961 10 milligram (mg) tablet twice daily on Week 1, 20 mg tablet twice daily on Week 2. After this titration, participants received 40 mg tablet twice daily from Week 3 to 8. Post treatment participants were followed approximately for 4 weeks. | 10 |
| PF-06882961 80 mg Participants with T2DM were randomized to receive PF-06882961 10 mg tablet twice daily on Week 1, 20 mg tablet twice daily on Week 2, 40 mg tablet twice daily on Week 3, 60 mg tablet twice daily on Week 4. After this titration, participants received 80 mg tablet twice daily from Week 5 to 8. Post treatment participants were followed approximately for 4 weeks. | 9 |
| PF-06882961 120 mg Participants with T2DM were randomized to receive PF-06882961 10 mg tablet twice daily on Week 1, 20 mg tablet twice daily on Week 2, 40 mg tablet twice daily on Week 3, 60 mg tablet twice daily on Week 4, 80 mg tablet twice daily on Week 5, 100 mg tablet twice daily on Week 6. After this titration, participants received 120 mg tablet twice daily from Week 7 to 8. Post treatment participants were followed approximately for 4 weeks. | 9 |
| Total | 37 |
Baseline characteristics
| Characteristic | Placebo | PF-06882961 40 mg | PF-06882961 80 mg | PF-06882961 120 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.6 Years STANDARD_DEVIATION 8.75 | 55.9 Years STANDARD_DEVIATION 10.04 | 58.0 Years STANDARD_DEVIATION 6.69 | 50.7 Years STANDARD_DEVIATION 7.5 | 55.8 Years STANDARD_DEVIATION 8.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 10 Participants | 9 Participants | 9 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 10 Participants | 9 Participants | 9 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 3 / 9 | 7 / 10 | 9 / 9 | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline
PR interval had following categories: maximum absolute PR interval \>=300 milliseconds (msec); when baseline PR interval \>200 msec and maximum increase from baseline in PR interval \>=25 percent; when baseline PR interval less than or equal to (\<=) 200 msec and maximum increase from baseline in PR interval \>=50 percent. QRS interval had following categories: maximum absolute QRS interval \>=140 msec; maximum increase from baseline in QRS interval \>=50 percent. QTC interval with Frederica's correction (QTCF) had following categories: absolute QTCF interval \>450 msec to \<=480 msec; absolute QTCF interval \>480 msec to \<=500 msec; absolute QTCF interval \>500 msec; QTCF interval increase from baseline \>=30 msec to \<=60 msec; QTCF interval increase from baseline \>60 msec.
Time frame: Baseline (1 Day before dosing) up to last dose (maximum up to Week 8)
Population: Safety analysis set included all participants who were randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute PR >=300 msec | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR >200 msec and maximum increase in PR >=25% | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR <=200 msec and maximum increase in PR >=50% | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute QRS >=140 msec | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum increase in QRS >=50% | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >450 msec to <=480 msec | 1 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >480 msec to <=500 msec | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF >500 msec | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >=30 msec to <=60 msec | 0 Participants |
| Placebo | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >60 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR <=200 msec and maximum increase in PR >=50% | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >=30 msec to <=60 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute QRS >=140 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum increase in QRS >=50% | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >450 msec to <=480 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >480 msec to <=500 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >60 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF >500 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute PR >=300 msec | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR >200 msec and maximum increase in PR >=25% | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF >500 msec | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >480 msec to <=500 msec | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >60 msec | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute PR >=300 msec | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute QRS >=140 msec | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >450 msec to <=480 msec | 1 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >=30 msec to <=60 msec | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR >200 msec and maximum increase in PR >=25% | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum increase in QRS >=50% | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR <=200 msec and maximum increase in PR >=50% | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum increase in QRS >=50% | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF >500 msec | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >450 msec to <=480 msec | 1 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >60 msec | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Absolute QTCF interval >480 msec to <=500 msec | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR >200 msec and maximum increase in PR >=25% | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Baseline PR <=200 msec and maximum increase in PR >=50% | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute QRS >=140 msec | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | Maximum absolute PR >=300 msec | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Electrocardiogram (ECG) Values and Increased ECG Values From Time-Matched Baseline | QTCF increase >=30 msec to <=60 msec | 0 Participants |
Primary
Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline
Supine systolic blood pressure (SBP) measured in millimeter of mercury (mmHg) had following categories: minimum of absolute SBP \<90 mmHg, maximum of SBP \>=30 mmHg decrease from baseline and maximum of SBP \>=30 mmHg increase from baseline. Supine diastolic blood pressure (DBP) measured in mmHg had following categories: minimum of absolute DBP \<50 mmHg, maximum of DBP \>20 mmHg decrease from baseline and maximum of DBP \>=20 mmHg increase from baseline. Supine pulse rate measured in beats per minute (BPM) had following categories: minimum of absolute supine pulse rate \<40 BPM and maximum of absolute supine pulse rate \>120 BPM. Baseline was defined as the time-matched value from the average of the triplicate recordings on Day -1.
Time frame: Baseline (1 Day before dosing) up to last dose (maximum up to Week 8)
Population: Safety analysis set included all participants who were randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute SBP <90 mmHg | 0 Participants |
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg decrease | 1 Participants |
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg increase | 3 Participants |
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute DBP <50 mmHg | 0 Participants |
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg decrease | 0 Participants |
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg increase | 1 Participants |
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute pulse rate <40 BPM | 0 Participants |
| Placebo | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of absolute pulse rate >120 BPM | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg increase | 2 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg decrease | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg decrease | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of absolute pulse rate >120 BPM | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute pulse rate <40 BPM | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute DBP <50 mmHg | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg increase | 2 Participants |
| PF-06882961 40 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute SBP <90 mmHg | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute pulse rate <40 BPM | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg increase | 3 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute DBP <50 mmHg | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg decrease | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg increase | 3 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of absolute pulse rate >120 BPM | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute SBP <90 mmHg | 0 Participants |
| PF-06882961 80 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg decrease | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg increase | 2 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute DBP <50 mmHg | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of SBP >=30 mmHg decrease | 1 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute SBP <90 mmHg | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg decrease | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of absolute pulse rate >120 BPM | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Minimum of absolute pulse rate <40 BPM | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Absolute Vital Signs (SBP, DBP and Pulse Rate) Values; Increased and Decreased Vital Signs (SBP, DBP) Values From Time-Matched Baseline | Maximum of DBP >=20 mmHg increase | 3 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities
Leukocytes (10\^9/liter \[L\]) bilirubin (micromol/L), glucose (millimoles \[mmol\]/L), triacylglycerol lipase (microkatals \[microkat\]/L): greater than (\>) 1.5\*upper limit normal (ULN); activated partial thromboplastin time (s): 1.1\*ULN; HDL cholesterol (mmol/L), thyroid stimulating hormone (TSH) (milliunits \[mU\]/L): less than (\<) 0.8\*lower limit normal (LLN); LDL cholesterol (mmol/L), urate (mmol/L): \>1.2\*ULN; triglycerides: \>1.3\*ULN; aspartate aminotransferase (microkat/L), alanine aminotransferase (microkat/L), gamma glutamyl transferase (microkat/L): \>3.0\*ULN; cholesterol (mmol/L): \>1.3\*ULN; urine glucose, ketones urine protein, urine hemoglobin, urobilinogen, nitrite, leukocyte esterase: greater than or equal to (\>=) 1; granular casts, hyaline casts: \>1.
Time frame: Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks)
Population: Safety analysis set included all participants who were randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | 9 Participants |
| PF-06882961 40 mg | Number of Participants With Clinical Laboratory Abnormalities | 10 Participants |
| PF-06882961 80 mg | Number of Participants With Clinical Laboratory Abnormalities | 8 Participants |
| PF-06882961 120 mg | Number of Participants With Clinical Laboratory Abnormalities | 9 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/ incapacity; congenital anomaly. Treatment emergent AEs were events between first dose of study drug and approximately 4 weeks after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs.
Time frame: Day 1 of dosing up to approximately 4 weeks after last dose (up to maximum of approximately 12 weeks)
Population: Safety analysis set included all participants who were randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 3 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| PF-06882961 40 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 7 Participants |
| PF-06882961 80 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 9 Participants |
| PF-06882961 80 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| PF-06882961 120 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with AEs | 9 Participants |
| PF-06882961 120 mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
Secondary
Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961
AUC24= Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24).
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1 and 56
Population: Pharmacokinetic (PK) parameter analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention and who had at least 1 of the PK parameters of interest calculated. This outcome measure reports AUC24 of PF-06882961, hence there is no data collected and analyzed for reporting arm Placebo. Here Number Analyzed signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961 | Day 1 | 414.4 Nanogram*hour per milliliter | Geometric Coefficient of Variation 58 |
| Placebo | Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961 | Day 56 | 2424 Nanogram*hour per milliliter | Geometric Coefficient of Variation 45 |
| PF-06882961 40 mg | Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961 | Day 1 | 500.3 Nanogram*hour per milliliter | Geometric Coefficient of Variation 58 |
| PF-06882961 40 mg | Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961 | Day 56 | 4691 Nanogram*hour per milliliter | Geometric Coefficient of Variation 75 |
| PF-06882961 80 mg | Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961 | Day 1 | 484.5 Nanogram*hour per milliliter | Geometric Coefficient of Variation 73 |
| PF-06882961 80 mg | Area Under the Plasma Concentration-time Profile From Zero to Time 24 Hours (AUC24) of PF-06882961 | Day 56 | 6953 Nanogram*hour per milliliter | Geometric Coefficient of Variation 148 |
Secondary
Maximum Plasma Concentration (Cmax) Observed of PF-06882961
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56
Population: PK parameter analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention and who had at least 1 of the PK parameters of interest calculated. This outcome measure reports Cmax of PF-06882961, hence there is no data collected and analyzed for reporting arm Placebo. Here Number Analyzed signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) Observed of PF-06882961 | Day 1 | 32.83 Nanogram per milliliter | Geometric Coefficient of Variation 55 |
| Placebo | Maximum Plasma Concentration (Cmax) Observed of PF-06882961 | Day 56 | 206.1 Nanogram per milliliter | Geometric Coefficient of Variation 54 |
| PF-06882961 40 mg | Maximum Plasma Concentration (Cmax) Observed of PF-06882961 | Day 1 | 45.89 Nanogram per milliliter | Geometric Coefficient of Variation 52 |
| PF-06882961 40 mg | Maximum Plasma Concentration (Cmax) Observed of PF-06882961 | Day 56 | 352.2 Nanogram per milliliter | Geometric Coefficient of Variation 75 |
| PF-06882961 80 mg | Maximum Plasma Concentration (Cmax) Observed of PF-06882961 | Day 1 | 39.35 Nanogram per milliliter | Geometric Coefficient of Variation 80 |
| PF-06882961 80 mg | Maximum Plasma Concentration (Cmax) Observed of PF-06882961 | Day 56 | 551.7 Nanogram per milliliter | Geometric Coefficient of Variation 153 |
Secondary
Terminal Phase Half-Life (t1/2) of PF-06882961
t1/2 was calculated as loge (2) per kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56
Population: PK parameter analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention and who had at least 1 of the PK parameters of interest calculated. This outcome measure reports t1/2 of PF-06882961, hence there is no data collected and analyzed for reporting arm Placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Phase Half-Life (t1/2) of PF-06882961 | 6.373 Hours | Standard Deviation 1.7404 |
| PF-06882961 40 mg | Terminal Phase Half-Life (t1/2) of PF-06882961 | 5.543 Hours | Standard Deviation 0.30827 |
| PF-06882961 80 mg | Terminal Phase Half-Life (t1/2) of PF-06882961 | 5.300 Hours | Standard Deviation 0.80594 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961
Time frame: Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14 and 24 hours post dose on Day 1; Pre-dose (0 hour), 1, 2, 4, 6, 8, 10, 12, 14, 24, 36 and 48 hours on Day 56
Population: PK parameter analysis set included all participants randomly assigned to study intervention who took at least 1 dose of study intervention and who had at least 1 of the PK parameters of interest calculated. This outcome measure reports Tmax of PF-06882961, hence there is no data collected and analyzed for reporting arm Placebo. Here Number Analyzed signifies participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961 | Day 1 | 12.0 Hours |
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961 | Day 56 | 12.0 Hours |
| PF-06882961 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961 | Day 1 | 12.0 Hours |
| PF-06882961 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961 | Day 56 | 12.9 Hours |
| PF-06882961 80 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961 | Day 1 | 12.0 Hours |
| PF-06882961 80 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06882961 | Day 56 | 12.0 Hours |