Trial Outcomes & Findings for Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients at Early Stage of the Disease (NCT NCT02847650)

Last Updated: 2020-11-23

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

Baseline (Day -1/randomization), Week 15

Results posted on

2020-11-23

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	29	28
Overall Study COMPLETED	25	22
Overall Study NOT COMPLETED	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
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

Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients at Early Stage of the Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PF-06649751 n=29 Participants 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.	Placebo n=28 Participants 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.	Total n=57 Participants Total of all reporting groups
Age, Continuous	64.76 years STANDARD_DEVIATION 8.34 • n=5 Participants	63.36 years STANDARD_DEVIATION 9.16 • n=7 Participants	64.07 years STANDARD_DEVIATION 8.71 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	14 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	25 Participants n=7 Participants	53 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PF-06649751 n=25 Participants 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.	Placebo n=22 Participants 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.
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	-4.3 units on a scale Standard Error 1.65

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	PF-06649751 n=29 Participants 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.	Placebo n=28 Participants 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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	25 Participants	18 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	PF-06649751 n=28 Participants 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.	Placebo n=28 Participants 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.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	19 Participants	19 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	PF-06649751 n=29 Participants 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.	Placebo n=28 Participants 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.
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Supine SBP <90 mmHg	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Standing SBP <90 mmHg	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Supine DBP <50 mmHg	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Standing DBP <50 mmHg	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Supine pulse rate <40 bpm	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Supine pulse rate >120 bpm	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Standing pulse rate <40 bpm	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Standing pulse rate >140 bpm	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum increase in standing DBP >=20 mmHg	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum increase in standing SBP >=30 mmHg	0 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum increase in supine DBP >=20 mmHg	0 Participants	1 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum increase in supine SBP >=30 mmHg	0 Participants	3 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum decrease in standing DBP >=20 mmHg	8 Participants	2 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum decrease in standing SBP >=30 mmHg	4 Participants	1 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum decrease in supine DBP >=20 mmHg	9 Participants	1 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria Maximum decrease in supine SBP >=30 mmHg	5 Participants	0 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria SBP postural difference(supine-standing) >=20mmHg	1 Participants	2 Participants
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria DBP postural difference(supine-standing) >=10mmHg	3 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06649751 n=29 Participants 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.	Placebo n=28 Participants 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.
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters PR interval >=300 msec	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters QRS duration >=140 msec	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters QT interval >=500 msec	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters QTcF interval >=450 msec to <480 msec	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters QTcF interval >=480 msec to <500 msec	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters QTcF interval >=500 msec	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters Percent increase in PR interval >=25/50%	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters Percent increase in QRS duration >=50%	0 Participants	0 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters Increase in QTcF interval >=30 msec to <60 msec	1 Participants	2 Participants
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters Increase in QTcF interval >=60 msec	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	PF-06649751 n=29 Participants 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.	Placebo n=28 Participants 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.
Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) Worsening suicidality	0 Participants	0 Participants
Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS) New onset suicidality	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	PF-06649751 n=29 Participants 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.	Placebo n=28 Participants 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.
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	1.1 units on a scale Standard Deviation 9.02
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	1.9 units on a scale Standard Deviation 9.49
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	-0.2 units on a scale Standard Deviation 5.38

SECONDARY outcome

Timeframe: Day 119

Population: All participants who received at least 1 dose of study treatment (PF-06649751 or placebo) and had PWC-20 evaluation.

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.

Outcome measures

Outcome measures
Measure	PF-06649751 n=28 Participants 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.	Placebo n=26 Participants 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.
Total Physician Withdrawal Checklist (PWC-20) Score	1.50 units on a scale Interval 0.0 to 12.0	1.00 units on a scale Interval 0.0 to 11.0

Adverse Events

PF-06649751

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PF-06649751 n=29 participants at risk 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.	Placebo n=28 participants at risk 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.
Psychiatric disorders Suicidal ideation	3.4% 1/29 • Number of events 1 • From first dose of study treatment up to 28 days after last dose (up to Day 133) The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study.	0.00% 0/28 • From first dose of study treatment up to 28 days after last dose (up to Day 133) The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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Restriction type: OTHER