Parkinson Disease
Conditions
Keywords
Early Parkinson Disease, Phase 2
Brief summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of PF-06649751 in Parkinson's disease patients at early stage of the disease.
Detailed description
The B7601011 study has a randomized, double-blind, placebo-controlled parallel group design. Approximately 88 subjects will be randomized to 2 treatment groups. Each subject will participate in the study for approximately 23 weeks including a 30 day screening period, 15 week double blind treatment period, and an approximately 28 day follow-up period.
Interventions
DRUGPlacebo
DRUGPF-06649751
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Females of non-childbearing potential and/or male subjects * Clinical diagnosis of Parkinson's disease. * Parkinson's Disease Hoehn & Yahr Stage I-III inclusive * Treatment naïve or history of prior incidental treatment with dopaminergic agents for no more than 28 days * Able to refrain from any Parkinson's disease medication not permitted by the protocol.
Exclusion criteria
* History or presence of atypical Parkinsonian syndrome. * Severe acute or chronic medical or psychiatric condition or cognitive impairment or laboratory abnormality. * Any condition possibly affecting drug absorption. * Participation in other studies involving investigational drug(s), or treatment with any investigational drug within 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score at Week 15 | Baseline (Day -1/randomization), Week 15 | MDS-UPDRS Part III was used to assess the motor signs of Parkinson's disease. It was comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question was anchored with 5 responses that were linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The MDS-UPDRS Part III total score range is 0-132. Higher score indicates more severe motor signs of Parkinson's disease. A negative change from baseline represents an improvement in motor function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Baseline (Day -1/randomization) up to Day 119 follow-up visit | Following safety laboratory parameters were assessed against pre-defined abnormality criteria: 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); chemistry (blood urea nitrogen/urea and creatinine, glucose , calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urine bilirubin, urobilinogen, urine creatinine, microscopy, and specific gravity). |
| Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Baseline (Day -1/randomization) up to Day 119 follow-up visit | Vital signs categorical summarization criteria: 1) supine and standing systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine and standing diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) standing pulse rate \<40 or \>140 bpm; 5) maximum change from baseline (increase or decrease) in supine and standing DBP greater than or equal to (\>=) 20 mmHg; 6) maximum change from baseline (increase or decrease) in supine and standing SBP \>=30 mmHg. Orthostatic hypotension criterion was defined as a decrease of \>=20 mmHg for SBP or \>=10 mmHg for DBP 2 minutes after standing from a supine position. |
| Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Baseline (Day -1/randomization) up to Day 119 follow-up visit | ECG categorical summarization criteria: 1) QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): \>=140 milliseconds (msec), \>=50% increase from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): \>=300 msec, \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of \>=500 msec; 4) QTcF interval (QT corrected for heart rate using Fridericia's formula): absolute value of 450 to \<480 msec, 480 to \<500 msec, \>=500 msec; an increase from baseline of 30 to \<60 msec or \>=60 msec. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | From first dose of study treatment up to 28 days after last dose (up to Day 133) | An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. |
| Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105 | Baseline (Day -1 or randomization); Days 35, 63, 105 | The QUIP-RS has 4 primary questions pertaining to commonly reported thoughts, urges/desires, and behaviors associated with impulsive-compulsive disorder , each applied to the 4 impulsive-compulsive disorders (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). Each question is anchored with the following 5 responses: Never (0), Rarely (1), Sometimes (2), Often (3), and Very Often (4). The scoring range for each item (ie, disorder) is 0-16. The QUIP-RS total score range is 0-64. Higher score indicates a greater level of the impulsive compulsive disorder. |
| Total Physician Withdrawal Checklist (PWC-20) Score | Day 119 | The PWC-20 is a 20-item reliable and sensitive instrument for the assessment of benzodiazepine-like discontinuation symptoms. The total PWC-20 score is the sum of 20 item scores and ranges between 0 and 60. The higher score indicates more frequent/severe symptoms. |
| Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) | Baseline (Day -1/randomization) up to Day 119 follow-up visit | The C-SSRS is an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Participants with new onset suicidality were those without suicidal ideation and behavior at baseline and reported any suicidal behavior or ideation post-baseline as assessed by C-CASA code mapped from C-SSRS data. Participants with worsening suicidality were those who moved to a lower numbered C-CASA category than was reported at baseline. |
Countries
France, Germany, Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-06649751 Eligible participants were up-titrated in a double-blind fashion to an optimal dose level of PF-06649751 according to a flexible dose titration scheme (from 0.25 mg to 15 mg once daily \[QD\]). The 15-week treatment period included 9 weeks of dose optimization and 6 weeks of stable dosing. Blinded PF-06649751 was provided as tablets for oral administration in the outpatient setting (each morning, daily for the duration of the treatment period). Reaching of the maximum allowed dose level (15 mg) was not mandatory; participants might achieve a satisfactory clinical response at a lower dose level. There was an additional follow-up period of 28 days following discontinuation of PF-06649751. | 29 |
| Placebo Matching placebo tablet for QD dosing in the 15-week double-blind treatment period. There was an additional follow-up period of 28 days following discontinuation of placebo. | 28 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | PF-06649751 |
|---|---|---|---|
| Age, Continuous | 63.36 years STANDARD_DEVIATION 9.16 | 64.07 years STANDARD_DEVIATION 8.71 | 64.76 years STANDARD_DEVIATION 8.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 54 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 53 Participants | 28 Participants |
| Sex: Female, Male Female | 14 Participants | 23 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 34 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 28 |
| other Total, other adverse events | 22 / 29 | 12 / 28 |
| serious Total, serious adverse events | 1 / 29 | 0 / 28 |
Outcome results
Primary
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score at Week 15
MDS-UPDRS Part III was used to assess the motor signs of Parkinson's disease. It was comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question was anchored with 5 responses that were linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The MDS-UPDRS Part III total score range is 0-132. Higher score indicates more severe motor signs of Parkinson's disease. A negative change from baseline represents an improvement in motor function.
Time frame: Baseline (Day -1/randomization), Week 15
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo) and had a baseline and Week 15 MDS-UPDRS score Part III.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PF-06649751 | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score at Week 15 | -9.0 units on a scale | Standard Error 1.54 |
| Placebo | Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score at Week 15 | -4.3 units on a scale | Standard Error 1.65 |
p-value: 0.040790% CI: [-8.6, -1]Mixed Models Analysis
Secondary
Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105
The QUIP-RS has 4 primary questions pertaining to commonly reported thoughts, urges/desires, and behaviors associated with impulsive-compulsive disorder , each applied to the 4 impulsive-compulsive disorders (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). Each question is anchored with the following 5 responses: Never (0), Rarely (1), Sometimes (2), Often (3), and Very Often (4). The scoring range for each item (ie, disorder) is 0-16. The QUIP-RS total score range is 0-64. Higher score indicates a greater level of the impulsive compulsive disorder.
Time frame: Baseline (Day -1 or randomization); Days 35, 63, 105
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo). Number Analyzed = Participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06649751 | Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105 | Change from baseline at Day 35 | 0.2 units on a scale | Standard Deviation 5.23 |
| PF-06649751 | Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105 | Change from baseline at Day 63 | -1.1 units on a scale | Standard Deviation 5.99 |
| PF-06649751 | Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105 | Change from baseline at Day 105 | -1.6 units on a scale | Standard Deviation 4.54 |
| Placebo | Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105 | Change from baseline at Day 35 | 1.9 units on a scale | Standard Deviation 9.49 |
| Placebo | Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105 | Change from baseline at Day 63 | 1.1 units on a scale | Standard Deviation 9.02 |
| Placebo | Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105 | Change from baseline at Day 105 | -0.2 units on a scale | Standard Deviation 5.38 |
Secondary
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters
ECG categorical summarization criteria: 1) QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): \>=140 milliseconds (msec), \>=50% increase from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): \>=300 msec, \>=25% increase when baseline is \> 200 msec or \>=50% increase when baseline is less than or equal to (\<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of \>=500 msec; 4) QTcF interval (QT corrected for heart rate using Fridericia's formula): absolute value of 450 to \<480 msec, 480 to \<500 msec, \>=500 msec; an increase from baseline of 30 to \<60 msec or \>=60 msec.
Time frame: Baseline (Day -1/randomization) up to Day 119 follow-up visit
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo). Number Analyzed represents the number of participants evaluable for each specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | PR interval >=300 msec | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QRS duration >=140 msec | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QT interval >=500 msec | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QTcF interval >=450 msec to <480 msec | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QTcF interval >=480 msec to <500 msec | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QTcF interval >=500 msec | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Percent increase in PR interval >=25/50% | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Percent increase in QRS duration >=50% | 0 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Increase in QTcF interval >=30 msec to <60 msec | 1 Participants |
| PF-06649751 | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Increase in QTcF interval >=60 msec | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Percent increase in QRS duration >=50% | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | PR interval >=300 msec | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QTcF interval >=500 msec | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QRS duration >=140 msec | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Increase in QTcF interval >=60 msec | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QT interval >=500 msec | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Percent increase in PR interval >=25/50% | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QTcF interval >=450 msec to <480 msec | 0 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | Increase in QTcF interval >=30 msec to <60 msec | 2 Participants |
| Placebo | Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters | QTcF interval >=480 msec to <500 msec | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Following safety laboratory parameters were assessed against pre-defined abnormality criteria: 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); chemistry (blood urea nitrogen/urea and creatinine, glucose , calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urine bilirubin, urobilinogen, urine creatinine, microscopy, and specific gravity).
Time frame: Baseline (Day -1/randomization) up to Day 119 follow-up visit
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo) and had at least 1 observation of the given laboratory test.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06649751 | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 19 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | 19 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Time frame: From first dose of study treatment up to 28 days after last dose (up to Day 133)
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06649751 | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 25 Participants |
| PF-06649751 | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 18 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria
Vital signs categorical summarization criteria: 1) supine and standing systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine and standing diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) standing pulse rate \<40 or \>140 bpm; 5) maximum change from baseline (increase or decrease) in supine and standing DBP greater than or equal to (\>=) 20 mmHg; 6) maximum change from baseline (increase or decrease) in supine and standing SBP \>=30 mmHg. Orthostatic hypotension criterion was defined as a decrease of \>=20 mmHg for SBP or \>=10 mmHg for DBP 2 minutes after standing from a supine position.
Time frame: Baseline (Day -1/randomization) up to Day 119 follow-up visit
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing DBP <50 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine SBP <90 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing SBP <90 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine DBP <50 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine pulse rate <40 bpm | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine pulse rate >120 bpm | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing pulse rate <40 bpm | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing pulse rate >140 bpm | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in standing DBP >=20 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in standing SBP >=30 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in supine DBP >=20 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in supine SBP >=30 mmHg | 0 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in standing DBP >=20 mmHg | 8 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in standing SBP >=30 mmHg | 4 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in supine DBP >=20 mmHg | 9 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in supine SBP >=30 mmHg | 5 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | SBP postural difference(supine-standing) >=20mmHg | 1 Participants |
| PF-06649751 | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | DBP postural difference(supine-standing) >=10mmHg | 3 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in standing SBP >=30 mmHg | 1 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in standing SBP >=30 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine SBP <90 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | DBP postural difference(supine-standing) >=10mmHg | 1 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing SBP <90 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in supine DBP >=20 mmHg | 1 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine DBP <50 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing DBP <50 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in supine DBP >=20 mmHg | 1 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine pulse rate <40 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in supine SBP >=30 mmHg | 3 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Supine pulse rate >120 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | SBP postural difference(supine-standing) >=20mmHg | 2 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing pulse rate <40 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in standing DBP >=20 mmHg | 2 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Standing pulse rate >140 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum decrease in supine SBP >=30 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria | Maximum increase in standing DBP >=20 mmHg | 0 Participants |
Secondary
Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Participants with new onset suicidality were those without suicidal ideation and behavior at baseline and reported any suicidal behavior or ideation post-baseline as assessed by C-CASA code mapped from C-SSRS data. Participants with worsening suicidality were those who moved to a lower numbered C-CASA category than was reported at baseline.
Time frame: Baseline (Day -1/randomization) up to Day 119 follow-up visit
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06649751 | Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) | Worsening suicidality | 0 Participants |
| PF-06649751 | Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) | New onset suicidality | 1 Participants |
| Placebo | Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) | Worsening suicidality | 0 Participants |
| Placebo | Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) | New onset suicidality | 0 Participants |
Secondary
Total Physician Withdrawal Checklist (PWC-20) Score
The PWC-20 is a 20-item reliable and sensitive instrument for the assessment of benzodiazepine-like discontinuation symptoms. The total PWC-20 score is the sum of 20 item scores and ranges between 0 and 60. The higher score indicates more frequent/severe symptoms.
Time frame: Day 119
Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo) and had PWC-20 evaluation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-06649751 | Total Physician Withdrawal Checklist (PWC-20) Score | 1.50 units on a scale |
| Placebo | Total Physician Withdrawal Checklist (PWC-20) Score | 1.00 units on a scale |