Idiopathic Parkinson's Disease
Conditions
Brief summary
This study is designed to assess safety, tolerability and pharmacokinetic data for multiple doses of PF-06669571 in subjects with idiopathic Parkinson's disease. In addition, this study will assess whether PF-06669571 is able to demonstrate superior efficacy compared with placebo in the treatment of the motor symptoms of idiopathic Parkinson's disease.
Interventions
DRUGPF-06669571
1 milligram (mg) QD for 3 days followed by 3 mg QD for 4 days
DRUGPlacebo
Placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a clinical diagnosis of idiopathic Parkinson's disease and presence of at least 2 out of 3 cardinal characteristics (tremor, rigidity and/or bradykinesia). * Must be Hoehn & Yahr Stage II-III inclusive and experiencing motor fluctuations in the form of end-of-dose wearing off during the morning hours or early morning akinesia. * Subjects should be able to recognize their wearing off symptoms and verify that they usually improve after their next dose of Parkinson's disease medication. Subjects should be able to recognize drug-induced dyskinesias and verify whether or not they are troublesome.
Exclusion criteria
\- History or clinical features consistent with an atypical parkinsonian syndrome, (for example: ataxia, dystonia, clinically significant orthostatic hypotension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory Abnormalities That Met Categorical Criteria for Concern (Without Regard to Baseline Abnormality) | Screening, Days 1, 4, and 7, and follow-up visit | Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),liver function(total bilirubin, direct bilirubin, aspartate, aspartate aminotransferase, alanine, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose) ,and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, qualitative ketones, qualitative bilirubin, nitrites, leukocyte esterase, urine urobilinogen, urine leukocyte, esterase and microscopy). |
| Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Screening, Days -1, 1, 7 and 8, and follow-up visit | The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine systolic BP (SBP) \>=30 millimeters of mercury (mmHg); Criterion B maximum increase from baseline in standing SBP \>=30 mmHg; Criterion C: maximum increase from baseline in supine diastolic BP(DBP) \>=20 mmHg; Criterion D: maximum increase from baseline in standing diastolic BP(DBP) \>=20 mmHg |
| Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Screening, Days -1, 1, 7 and 8, and follow-up visit | The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine systolic BP (SBP) \>=30 mmHg; Criterion B: maximum decrease from baseline in standing SBP \>=30 mmHg; Criterion C: maximum decrease from baseline in supine diastolic BP(DBP) \>=20 mmHg; Criterion D: maximum decrease from baseline in standing diastolic BP(DBP) \>=20 mmHg |
| Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Screening, Days 1, 7, and 8, and follow-up visit | The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>=300 msec; Criterion B: maximum QRs complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) \>=140 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-\<480 msec; Criterion D: maximum QTcF interval 480-\<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) \>=500 msec |
| Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Screening, Days 1, 7, and 8, and follow-up visit | Number of participants with ECG(standard 12-lead) meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>=25/50%; Criterion B: maximum QRs complex increase from baseline PctChg \>=50%; Criterion C: maximum QTcF interval increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTcF interval increase from baseline change \>=60 msec. |
| Maximum Percent Change From Baseline in Movement Disorder Society-Sponsor Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at Day 7. | Day 7 | The total MDS-UPDRS score is the most common method of evaluating the severity of Parkinson's disease across behaviors, activities of daily living, motor abilities, and other complications of Parkinson's disease. The MDS-UPDRS focuses primarily on measuring impairments associated with Parkinson's disease, with subsections organized according to motor and non-motor aspects of the disease. Part III assesses the motor signs of Parkinson's disease. Higher total scores indicate more severe motor signs of Parkinson's disease. Negative changes from baseline indicate improvement. MDS-UPDRS Part III total motor score is comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question is anchored with five responses that are linked to commonly accepted clinical terms: 0 = normal, 1 = slight, 2 = mild, 3 = moderate and 4 = severe. |
| Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | Day -2, Day 8, and follow-up visit (Day 7 - 14 after last dose of PF-06669571) | The number of participants in each C-CASA category was mapped from Columbia-Suicide Severity Rating Scale (C-SSRS) data. C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of Yes on actual attempt), preparatory acts toward imminent suicidal behavior (3) (Yes on preparatory acts or behavior), suicidal ideation (4) (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 or some intent to act, with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (Yes on Has subject engaged in non-suicidal self-injurious behavior). |
| Number of Participants With New Onset and Worsening of Post-Baseline Suicidality. | Day 8 or follow-up visit (Day 7 - 14 after last dose of PF-06669571) | Number of participants with new onset and worsening of post-baseline suicidality was reported |
| Number of Participants With Treatment Emergent Adverse Events (All Causalities) | Day 1 to 28 calendar days after the last dose of investigational product | An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. |
| Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Screening, Days -1, 1, 7 and 8, and follow-up visit | Number of participants with supine and standing vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for supine/standing systolic blood pressure (SBP), supine/standing diastolic blood pressure (DBP), and supine/standing pulse rate. Number of participants with vital signs data meeting the following criteria was reported: (1) absolute supine SBP \<90 millimeters of mercury (mmHg); (2) absolute standing SBP \<90 mmHg; (3)absolute supine DBP\<50mmHg; (4)absolute standing DBP\<50mmHg (5) absolute supine pulse rate \<40 beats per minute (bpm); (6) absolute supine pulse rate \>120 bpm;(7) absolute standing pulse rate \<40 bpm; (8) absolute standing pulse rate \>140 bpm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Curve From Time Zero to 12 Hours (AUC12) of PF-06669571 on Day 1 and Day 7 | 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7 | AUC12 of PF-06669571 refers to the area under the curve from time zero to 12 hours post dose on Day 1 and Day 7. AUC12 was determined by using linear/log trapezoidal method. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06669571 on Day 1 and Day 7 | 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7 | Tmax of PF-06669571 was observed directly from data on Day 1 and Day 7, as time of first occurrence. |
| Area Under Curve From Time Zero to 24 Hours (AUC24) of PF-06669571 on Day 7 | 0, 1, 3, 5, 8, 12 and 24 hours post-dose on Day 7 | AUC24 of PF-06669571 refers to the area under the curve from time zero to 24 hours post dose on Day 7. AUC24 was determined by using linear/log trapezoidal method |
| Maximum Observed Plasma Concentration (Cmax) of PF-06669571 on Day 1 and Day 7 | 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7 | Cmax of PF-06669671 was observed directly from data on Day 1 and Day 7 |
Countries
United States
Participant flow
Pre-assignment details
A total of 20 participants were randomized, 19 participants were treated. One participant was randomized but withdrew consent before receiving any treatment. This subject was not included in any analysis set.
Participants by arm
| Arm | Count |
|---|---|
| PF-06669571 0.5 mg PF-06669571 0.5 mg was orally administered on Day 1 through Day 7 as tablets. Participants swallowed 2 tablets on Days 1-3 (1 mg total) and 6 tablets (3 mg total) on Days 4-7 once daily, with ambient temperature water to a total volume of approximately 240 mL. A follow-up visit of 7-14 days after last dose of the treatment was completed. | 10 |
| Placebo Placebo matched to PF-06669571 was orally administered on Day 1 through Day 7 as tablets. Participants swallowed 6 tablets everyday with ambient temperature water to a total volume of approximately 240 mL. A follow-up visit of 7-14 days after last dose of the treatment was completed. | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | PF-06669571 0.5 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 7.4 | 67.9 years STANDARD_DEVIATION 5.9 | 66.6 years STANDARD_DEVIATION 6.6 |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 10 | 5 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Maximum Percent Change From Baseline in Movement Disorder Society-Sponsor Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at Day 7.
The total MDS-UPDRS score is the most common method of evaluating the severity of Parkinson's disease across behaviors, activities of daily living, motor abilities, and other complications of Parkinson's disease. The MDS-UPDRS focuses primarily on measuring impairments associated with Parkinson's disease, with subsections organized according to motor and non-motor aspects of the disease. Part III assesses the motor signs of Parkinson's disease. Higher total scores indicate more severe motor signs of Parkinson's disease. Negative changes from baseline indicate improvement. MDS-UPDRS Part III total motor score is comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question is anchored with five responses that are linked to commonly accepted clinical terms: 0 = normal, 1 = slight, 2 = mild, 3 = moderate and 4 = severe.
Time frame: Day 7
Population: All enrolled participants who started treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PF-06669571 0.5 mg | Maximum Percent Change From Baseline in Movement Disorder Society-Sponsor Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at Day 7. | -19.24 Percentage | Standard Error 7.21 |
| Placebo | Maximum Percent Change From Baseline in Movement Disorder Society-Sponsor Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III at Day 7. | -14.21 Percentage | Standard Error 7.6 |
p-value: 0.6382Mixed Models Analysis
Primary
Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit
The number of participants in each C-CASA category was mapped from Columbia-Suicide Severity Rating Scale (C-SSRS) data. C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of Yes on actual attempt), preparatory acts toward imminent suicidal behavior (3) (Yes on preparatory acts or behavior), suicidal ideation (4) (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 or some intent to act, with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7) (Yes on Has subject engaged in non-suicidal self-injurious behavior).
Time frame: Day -2, Day 8, and follow-up visit (Day 7 - 14 after last dose of PF-06669571)
Population: All enrolled participants who started treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06669571 0.5 mg | Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | Day -2 | 0 participants |
| PF-06669571 0.5 mg | Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | Day 8 | 0 participants |
| PF-06669571 0.5 mg | Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | Follow-up visit | 0 participants |
| Placebo | Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | Day -2 | 0 participants |
| Placebo | Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | Day 8 | 0 participants |
| Placebo | Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category by Study Visit on Day -2, Day 8 or Early Withdrawal, and Early Withdrawal/Follow-Up Visit | Follow-up visit | 0 participants |
Primary
Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value)
The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) \>=300 msec; Criterion B: maximum QRs complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) \>=140 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-\<480 msec; Criterion D: maximum QTcF interval 480-\<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) \>=500 msec
Time frame: Screening, Days 1, 7, and 8, and follow-up visit
Population: All enrolled participants who started treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06669571 0.5 mg | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion A | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion B | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion C | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion D | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion E | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion C | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion A | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion D | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion B | 0 participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern (Absolute Value) | Criterion E | 0 participants |
Primary
Number of Participants With Laboratory Abnormalities That Met Categorical Criteria for Concern (Without Regard to Baseline Abnormality)
Number of participants with a laboratory abnormality meeting specified criteria. The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),liver function(total bilirubin, direct bilirubin, aspartate, aspartate aminotransferase, alanine, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose) ,and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, qualitative ketones, qualitative bilirubin, nitrites, leukocyte esterase, urine urobilinogen, urine leukocyte, esterase and microscopy).
Time frame: Screening, Days 1, 4, and 7, and follow-up visit
Population: All enrolled participants who started treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06669571 0.5 mg | Number of Participants With Laboratory Abnormalities That Met Categorical Criteria for Concern (Without Regard to Baseline Abnormality) | 8 participants |
| Placebo | Number of Participants With Laboratory Abnormalities That Met Categorical Criteria for Concern (Without Regard to Baseline Abnormality) | 5 participants |
Primary
Number of Participants With New Onset and Worsening of Post-Baseline Suicidality.
Number of participants with new onset and worsening of post-baseline suicidality was reported
Time frame: Day 8 or follow-up visit (Day 7 - 14 after last dose of PF-06669571)
Population: All enrolled participants who started treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06669571 0.5 mg | Number of Participants With New Onset and Worsening of Post-Baseline Suicidality. | 0 participants |
| Placebo | Number of Participants With New Onset and Worsening of Post-Baseline Suicidality. | 0 participants |
Primary
Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline)
The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in supine systolic BP (SBP) \>=30 mmHg; Criterion B: maximum decrease from baseline in standing SBP \>=30 mmHg; Criterion C: maximum decrease from baseline in supine diastolic BP(DBP) \>=20 mmHg; Criterion D: maximum decrease from baseline in standing diastolic BP(DBP) \>=20 mmHg
Time frame: Screening, Days -1, 1, 7 and 8, and follow-up visit
Population: All enrolled participants who started treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion A | 5 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion B | 4 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion C | 3 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion D | 3 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion D | 2 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion A | 3 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion C | 3 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities (Decrease From Baseline) | Criterion B | 2 participants |
Primary
Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values)
Number of participants with supine and standing vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for supine/standing systolic blood pressure (SBP), supine/standing diastolic blood pressure (DBP), and supine/standing pulse rate. Number of participants with vital signs data meeting the following criteria was reported: (1) absolute supine SBP \<90 millimeters of mercury (mmHg); (2) absolute standing SBP \<90 mmHg; (3)absolute supine DBP\<50mmHg; (4)absolute standing DBP\<50mmHg (5) absolute supine pulse rate \<40 beats per minute (bpm); (6) absolute supine pulse rate \>120 bpm;(7) absolute standing pulse rate \<40 bpm; (8) absolute standing pulse rate \>140 bpm.
Time frame: Screening, Days -1, 1, 7 and 8, and follow-up visit
Population: All enrolled participants who started treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Diastolic BP <50 mmHg | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Pulse Rate >120 BPM | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Systolic BP <90 mmHg | 1 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Pulse Rate <40 BPM | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Diastolic BP <50 mmHg | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Pulse Rate >140 BPM | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Pulse Rate <40 BPM | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Systolic BP <90 mmHg | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Diastolic BP <50 mmHg | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Systolic BP <90 mmHg | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Systolic BP <90 mmHg | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Diastolic BP <50 mmHg | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Pulse Rate <40 BPM | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Supine Pulse Rate >120 BPM | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Pulse Rate <40 BPM | 0 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Absolute Values) | Standing Pulse Rate >140 BPM | 0 participants |
Primary
Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline)
The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in supine systolic BP (SBP) \>=30 millimeters of mercury (mmHg); Criterion B maximum increase from baseline in standing SBP \>=30 mmHg; Criterion C: maximum increase from baseline in supine diastolic BP(DBP) \>=20 mmHg; Criterion D: maximum increase from baseline in standing diastolic BP(DBP) \>=20 mmHg
Time frame: Screening, Days -1, 1, 7 and 8, and follow-up visit
Population: All enrolled participants who started treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion A | 1 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion B | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion C | 0 participants |
| PF-06669571 0.5 mg | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion D | 1 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion D | 1 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion A | 1 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion C | 1 participants |
| Placebo | Number of Participants With Supine and Standing Vital Sign Abnormalities of Potential Clinical Concern (Increase From Baseline) | Criterion B | 1 participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (All Causalities)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.
Time frame: Day 1 to 28 calendar days after the last dose of investigational product
Population: All enrolled participants who started treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06669571 0.5 mg | Number of Participants With Treatment Emergent Adverse Events (All Causalities) | 6 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (All Causalities) | 5 participants |
Primary
Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline)
Number of participants with ECG(standard 12-lead) meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)\>=25/50%; Criterion B: maximum QRs complex increase from baseline PctChg \>=50%; Criterion C: maximum QTcF interval increase from baseline 30\<=change\<60 msec; Criterion D: maximum QTcF interval increase from baseline change \>=60 msec.
Time frame: Screening, Days 1, 7, and 8, and follow-up visit
Population: All enrolled participants who started treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06669571 0.5 mg | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion D | 0 participants |
| PF-06669571 0.5 mg | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion C | 2 participants |
| PF-06669571 0.5 mg | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion A | 0 participants |
| PF-06669571 0.5 mg | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion B | 0 participants |
| Placebo | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion D | 0 participants |
| Placebo | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion B | 0 participants |
| Placebo | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion A | 0 participants |
| Placebo | Primary: Number of Participants With Electrocardiogram (ECG) That Met Categorical Criteria for Concern(Increase From Baseline) | Criterion C | 0 participants |
Secondary
Area Under Curve From Time Zero to 12 Hours (AUC12) of PF-06669571 on Day 1 and Day 7
AUC12 of PF-06669571 refers to the area under the curve from time zero to 12 hours post dose on Day 1 and Day 7. AUC12 was determined by using linear/log trapezoidal method.
Time frame: 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7
Population: The PF-06669571 PK parameter analysis set was used for this analysis, and it was defined as all subjects randomized and treated who have at least 1 of the PK parameters of interest measured.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06669571 0.5 mg | Area Under Curve From Time Zero to 12 Hours (AUC12) of PF-06669571 on Day 1 and Day 7 | Day 7 | 917.5 ng*hr/mL | Geometric Coefficient of Variation 35 |
| PF-06669571 0.5 mg | Area Under Curve From Time Zero to 12 Hours (AUC12) of PF-06669571 on Day 1 and Day 7 | Day 1 | 150.8 ng*hr/mL | Geometric Coefficient of Variation 28 |
Secondary
Area Under Curve From Time Zero to 24 Hours (AUC24) of PF-06669571 on Day 7
AUC24 of PF-06669571 refers to the area under the curve from time zero to 24 hours post dose on Day 7. AUC24 was determined by using linear/log trapezoidal method
Time frame: 0, 1, 3, 5, 8, 12 and 24 hours post-dose on Day 7
Population: The PF-06669571 PK parameter analysis set was used for this analysis, and it was defined as all subjects randomized and treated who have at least 1 of the PK parameters of interest measured.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06669571 0.5 mg | Area Under Curve From Time Zero to 24 Hours (AUC24) of PF-06669571 on Day 7 | 1626 ng*hr/mL | Geometric Coefficient of Variation 38 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06669571 on Day 1 and Day 7
Cmax of PF-06669671 was observed directly from data on Day 1 and Day 7
Time frame: 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7
Population: The PF-06669571 pharmacokinetics(PK) concentration analysis set was used for this analysis, and it was defined as all subjects randomized and treated who have at least 1 measureable concentration of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06669571 0.5 mg | Maximum Observed Plasma Concentration (Cmax) of PF-06669571 on Day 1 and Day 7 | Day 1 | 16.87 ng/mL | Geometric Coefficient of Variation 30 |
| PF-06669571 0.5 mg | Maximum Observed Plasma Concentration (Cmax) of PF-06669571 on Day 1 and Day 7 | Day 7 | 92.51 ng/mL | Geometric Coefficient of Variation 31 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06669571 on Day 1 and Day 7
Tmax of PF-06669571 was observed directly from data on Day 1 and Day 7, as time of first occurrence.
Time frame: 0, 1, 3, 5, 8 and 12 hours post-dose on both Day 1 and Day 7
Population: The PF-06669571 PK concentration analysis set was used for this analysis, and it was defined as all subjects randomized and treated who have at least 1 measureable concentration of interest.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| PF-06669571 0.5 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06669571 on Day 1 and Day 7 | Day 1 | 3.35 hr |
| PF-06669571 0.5 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06669571 on Day 1 and Day 7 | Day 7 | 3.19 hr |