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    Clinical Trial Results:
    A 15-Week, Phase 2, Double Blind, Randomized, Placebo-Controlled, Dose Ranging Study to Investigate the Efficacy, Safety and Tolerability of PF-06649751 in Subjects With Motor Fluctuations Due to Parkinson’s Disease

    Summary
    EudraCT number
    		 2015-004912-39
    Trial protocol
    		 DE   ES  
    Global end of trial date
    10 Nov 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Nov 2018
    First version publication date
    14 Nov 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B7601003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02687542
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer Clinical Trials.gov Call Center, Pfizer, Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 May 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Nov 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Nov 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective of this study was to to evaluate the effect on motor symptoms of PF-06649751 administered once daily as adjunctive treatment with stable doses of L-Dopa in Parkinson’s disease; and to determine the therapeutic window for motor symptom improvement of PF-06649751 administered once daily, ie, determining a dose, or a range of doses, for adequate control of motor symptoms.
    Protection of trial subjects
    This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
    Background therapy
    		 L-Dopa is one of the currently available pharmacological treatment strategies for Parkinson’s disease. L-Dopa therapy provides increased dopamine levels in a transient and highly variable pulse and affords rapid onset improvement of motor symptoms for a limited duration. More than 40% of patients on L-Dopa experience motor fluctuations and dyskinesias after more than 3 to 5 years of therapy. Following an initial titration phase in this study, which was intended to mitigate potential dopaminergic adverse events such as nausea and vomiting, fixed doses of PF-06649751 were evaluated as adjunctive treatment with L-Dopa. Subjects received L‑dopa in accordance with instructions provided in the product labelling information, at a dose and frequency per the instructions of the investigator.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Mar 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Japan: 9
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    United States: 75
    Worldwide total number of subjects
    108
    EEA total number of subjects
    21
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    50
    From 65 to 84 years
    58
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 200 subjects were screened, of which 108 subjects were assigned to treatment: 23 subjects to placebo, 13 subjects to PF-06649751 1 mg once daily (QD), 15 subjects to 3 mg QD, 13 subjects to 7 mg QD and 44 subjects to 15 mg QD.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 The subjects swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for subject's safety.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    3 Placebo tablets were taken once daily (QD) at approximately the same time each morning within approximately 5 minutes.

    Arm title
    		 PF-06649751 1 mg QD
    Arm description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject's safety.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-06649751
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    3 tablets containing 1 mg PF-06649751 were taken QD at approximately the same time each morning within approximately 5 minutes.

    Arm title
    		 PF-06649751 3 mg QD
    Arm description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-06649751
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    3 tablets containing 3 mg PF-06649751 were taken QD at approximately the same time each morning within approximately 5 minutes.

    Arm title
    		 PF-06649751 7 mg QD
    Arm description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-06649751
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    3 tablets containing 7 mg PF-06649751 were taken QD at approximately the same time each morning within approximately 5 minutes.

    Arm title
    		 PF-06649751 15 mg QD
    Arm description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-06649751
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    3 tablets containing 15 mg PF-06649751 were taken QD at approximately the same time each morning within approximately 5 minutes.

    Number of subjects in period 1
    		Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Started
    23
    13
    15
    13
    44
    Completed
    15
    1
    1
    3
    24
    Not completed
    8
    12
    14
    10
    20
         Consent withdrawn by subject
    -
    1
    1
    2
    4
         Adverse event, non-fatal
    3
    1
    3
    2
    9
         Other
    5
    9
    10
    6
    5
         Lost to follow-up
    -
    -
    -
    -
    1
         Medication error without associated AEs
    -
    -
    -
    -
    1
         Protocol deviation
    -
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 The subjects swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for subject's safety.

    Reporting group title
    PF-06649751 1 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject's safety.

    Reporting group title
    PF-06649751 3 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Reporting group title
    PF-06649751 7 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Reporting group title
    PF-06649751 15 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Reporting group values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD Total
    Number of subjects
    		 23 13 15 13 44 108
    Age categorical
    Units: Subjects
        Adults (< 65 years)
    		 8 5 9 3 25 50
        From 65-74 years
    		 11 4 5 7 14 41
        From 75-84 years
    		 4 4 1 3 5 17
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.04 ( 8.79 ) 66.92 ( 8.79 ) 63.80 ( 7.76 ) 67.77 ( 9.36 ) 63.41 ( 8.47 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 6 6 6 4 18 40
        Male
    		 17 7 9 9 26 68
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 1 0 1
        Asian
    		 1 0 2 1 6 10
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0
        Black or African American
    		 2 1 0 2 1 6
        White
    		 20 12 12 9 36 89
        Other
    		 0 0 1 0 1 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 3 1 1 3 11
        Not Hispanic or Latino
    		 20 10 13 12 40 95
        Unknown
    		 0 0 1 0 1 2

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 The subjects swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for subject's safety.

    Reporting group title
    PF-06649751 1 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject's safety.

    Reporting group title
    PF-06649751 3 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Reporting group title
    PF-06649751 7 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Reporting group title
    PF-06649751 15 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Primary: Change From Baseline in Daily OFF Time at Week 10

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    End point title
    		 Change From Baseline in Daily OFF Time at Week 10
    End point description
    A paper Hauser diary was utilized to record motor state for half-hour intervals. Subjects completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization). The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit. Analysis population was Full Analysis Set consisting of all subjects randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). n in the following table represents the number of evaluable subjects in each arm.
    End point type
    Primary
    End point timeframe
    Week 10; Baseline was defined as the average daily OFF time (using 3 Hauser subject diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0).
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    21
    7
    9
    9
    41
    Units: Hours
    least squares mean (standard error)
        Change at Week 10 (n=16, 3, 2, 5 and 25)
    -0.969 ( 0.4092 )
    -1.173 ( 0.3482 )
    -1.316 ( 0.3289 )
    -1.480 ( 0.3460 )
    -1.663 ( 0.4297 )
    Statistical analysis title
    		 Bayesian Dose Response Analysis
    Comparison groups
    Placebo v PF-06649751 15 mg QD
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.5776 [2]
    Method
    		 Bayesian Dose Response Analysis
    Parameter type
    		 Bayesian Dose Reponse Estimate
    Point estimate
    -0.693
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.713
         upper limit
    		 0.304
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6162
    Notes
    [1] - Estimate and 90% credible interval of Bayesian dose response difference from placebo
    [2] - Bayesian Predictive Test for Emax (the additive increase over Placebo in the response of PF-06649751 at a theoretically infinite dose) Monotonicity

    Secondary: Change From Baseline in Daily OFF Time

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    End point title
    		 Change From Baseline in Daily OFF Time
    End point description
    A paper Hauser diary was utilized to record motor state for half-hour intervals. Subjects completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization). The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit. Analysis population was Full Analysis Set consisting of all subjects randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). (n in the following table stands for number of subjects evaluable for each treatment arm). Results at Week 15 should be interpreted with caution given almost half the subjects were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.
    End point type
    Secondary
    End point timeframe
    Weeks 3, 5, 10 and 15; Baseline was defined as the average daily OFF time (using 3 Hauser subject diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0).
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    21
    7
    9
    9
    41
    Units: Hours
    least squares mean (standard error)
        Change at Week 3 (n=18, 6, 8, 6 and 37)
    -0.67 ( 0.620 )
    -0.82 ( 1.237 )
    -0.55 ( 1.091 )
    -1.82 ( 1.182 )
    -1.01 ( 0.464 )
        Change at Week 5 (n=17, 5, 6, 7 and 32)
    -0.63 ( 0.490 )
    -2.04 ( 1.054 )
    -2.23 ( 0.964 )
    -1.41 ( 0.937 )
    -1.24 ( 0.392 )
        Change at Week 10 (n=16, 3, 2, 5 and 25)
    -0.99 ( 0.628 )
    -0.60 ( 1.423 )
    -1.00 ( 1.508 )
    -2.07 ( 1.187 )
    -1.63 ( 0.502 )
        Change at Week 15 (n=7, 1, 1, 3, and 14)
    1.05 ( 1.063 )
    -0.67 ( 2.960 )
    -2.75 ( 2.936 )
    -1.09 ( 1.687 )
    -2.47 ( 0.793 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Daily ON Time With Troublesome Dyskinesia

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    End point title
    		 Change From Baseline in Daily ON Time With Troublesome Dyskinesia
    End point description
    A paper Hauser diary was utilized to record motor state for half-hour intervals.The subjects answered the Hauser diary on whether they had been ON with troublesome dyskinesia.A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days.On the days recording the home diary, subjects made an entry every 30 minutes during their normal waking time and upon awakening from time asleep.The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit.Full Analysis Set including all subjects randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). (n in the following table stands for number of subjects evaluable for each treatment arm).Results at Week15 should be interpreted with caution given almost half subjects were not available for this analysis at Week15 compared to Week10 and complicated protocol changes impacting study design after Week10.
    End point type
    Secondary
    End point timeframe
    Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time with Troublesome Dyskinesia (using 3 Hauser subject diary Days) prior to Day -1 (study derived day and equalled to nominal visit Day 0).
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    21
    7
    9
    9
    41
    Units: Hours
    least squares mean (standard error)
        Change at Week 3 (n=18, 6, 8, 6 and 37)
    0.17 ( 0.236 )
    0.07 ( 0.467 )
    0.19 ( 0.417 )
    0.01 ( 0.464 )
    0.23 ( 0.179 )
        Change at Week 5 (n=17, 5, 6, 7 and 32)
    0.23 ( 0.198 )
    -0.21 ( 0.415 )
    -0.02 ( 0.388 )
    0.45 ( 0.363 )
    0.03 ( 0.162 )
        Change at Week 10 (n=16, 3, 2, 5 and 25)
    0.13 ( 0.191 )
    0.24 ( 0.464 )
    0.32 ( 0.529 )
    -0.39 ( 0.389 )
    0.13 ( 0.167 )
        Change at Week 15 (n=7, 1,1, 3 and 14)
    0.01 ( 0.642 )
    -0.43 ( 1.349 )
    -0.29 ( 1.263 )
    0.54 ( 1.071 )
    -0.21 ( 0.463 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Daily ON Time Without Troublesome Dyskinesia

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    End point title
    		 Change From Baseline in Daily ON Time Without Troublesome Dyskinesia
    End point description
    A paper Hauser diary was utilized to record motor state for half hour intervals.The subjects answered the Hauser diary on whether they had been ON without troublesome dyskinesia.A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days.On the days recording the home diary, subjects made an entry every 30 minutes during their normal waking time and upon awakening from time asleep.The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit. Full Analysis Set including all subjects randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary).(n in the following table is number of subjects evaluable for each treatment arm)Results at Week15 should be interpreted with caution given almost half subjects were not available for this analysis at Week15 compared to Week10 and complicated protocol changes impacting study design after Week10.
    End point type
    Secondary
    End point timeframe
    Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time without Troublesome Dyskinesia (using 3 Hauser subject diary days) prior to Day -1 (study derived day and equalled to nominal visit Day 0).
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    21
    7
    9
    9
    41
    Units: Hours
    least squares mean (standard error)
        Change at Week 3 (n=18, 6, 8, 6 and 37)
    0.61 ( 0.577 )
    1.74 ( 1.173 )
    -0.49 ( 1.047 )
    1.93 ( 1.128 )
    0.77 ( 0.443 )
        Change at Week 5 (n=17, 5, 6, 7 and 32)
    0.02 ( 0.548 )
    2.39 ( 1.150 )
    1.31 ( 1.058 )
    1.12 ( 1.029 )
    1.31 ( 0.436 )
        Change at Week 10 (n=16, 3, 2, 5 and 25)
    0.61 ( 0.618 )
    0.92 ( 1.413 )
    0.45 ( 1.598 )
    2.64 ( 1.194 )
    1.65 ( 0.508 )
        Change at Week 15 (n=7, 1, 1, 3 and 14)
    -0.81 ( 1.099 )
    0.37 ( 2.999 )
    -4.48 ( 3.192 )
    0.94 ( 1.781 )
    1.50 ( 0.825 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III

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    End point title
    		 Change From Baseline in Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III
    End point description
    MDS-UPDRS Part III assessed the motor signs of Parkinson’s disease and was administered by the investigator.It consisted 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 are linked to commonly accepted clinical terms:0=normal,1=slight,2=mild,3=moderate,and 4=severe.Higher total scores indicated more severe motor signs of Parkinson’s disease.There were 4 subscales:The tremor subscale(Score:0–36);The rigidity subscale(Score:0-20);The bradykinesia subscale(Score:0-36);The Postural Instability and Gait Disorder subscale(Score:0-12).Full Analysis Set consisting of all subjects randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary).(n is number of subjects evaluable for each treatment arm) Results at Week 15 should be interpreted with caution given almost half the subjects were not available for this analysis as compared to Week 10.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 3, 4, 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    21
    7
    9
    9
    41
    Units: Scale
    least squares mean (standard error)
        Change at Week 1 (n=21, 7, 9, 9 and 41)
    -3.90 ( 2.054 )
    -4.44 ( 3.965 )
    -4.61 ( 3.593 )
    -1.90 ( 3.594 )
    -3.22 ( 1.524 )
        Change at Week 2 (n=11, 1, 0, 1 and 20)
    -0.95 ( 2.078 )
    -15.78 ( 6.252 )
    99999 ( 99999 )
    0.56 ( 6.129 )
    -3.70 ( 1.584 )
        Change at Week 3 (n=10, 1, 0, 0 and 20)
    -3.80 ( 2.848 )
    -12.39 ( 8.240 )
    99999 ( 99999 )
    99999 ( 99999 )
    -3.06 ( 2.069 )
        Change at Week 4 (n=18, 7, 9, 9 and 37)
    -6.28 ( 2.182 )
    -0.84 ( 3.940 )
    -2.48 ( 3.572 )
    -2.91 ( 3.575 )
    -6.05 ( 1.574 )
        Change at Week 5 (n=18, 6, 6, 8 and 34)
    -5.12 ( 2.386 )
    -6.14 ( 4.414 )
    3.10 ( 4.347 )
    -1.22 ( 3.935 )
    -4.86 ( 1.765 )
        Change at Week 10 (n=17, 5, 2, 6 and 30)
    -5.09 ( 1.967 )
    -2.21 ( 3.902 )
    5.77 ( 5.365 )
    -2.36 ( 3.607 )
    -9.32 ( 1.526 )
        Change at Week 15 (n=8, 1, 1, 3 and 15)
    -0.18 ( 3.170 )
    7.72 ( 8.660 )
    2.09 ( 9.495 )
    -5.44 ( 5.364 )
    -1.84 ( 2.519 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score

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    End point title
    		 Change From Baseline in Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score
    End point description
    The MDS-UPDRS included components assessed by the investigator as well as sections completed by the subject.Part I (Non-Motor Aspects of Experiences of daily Living) assessed non motor experiences of daily living(Score: 0-52); Part II (Motor Aspects of Experiences of Daily Living) assessed motor experiences of daily living.There were additional 13 questions that were also part of the Questionnaire completed by the subject(Score: 0-52); Part IV (Motor Complications) assessed motor complications, dyskinesias, and motor fluctuations using historical and objective information(Score: 0-24); MDS-UPDRS Total Score: The sum of Parts I, II, III, and IV.Full Analysis Set included all subjects randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). (n is number of subjects evaluable for each treatment arm) Results at Week 15 should be interpreted with caution given almost half the subjects were not available for this analysis as compared to Week 10.
    End point type
    Secondary
    End point timeframe
    Weeks 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    21
    7
    9
    9
    41
    Units: Scale
    arithmetic mean (standard deviation)
        Change at Week 5 (Part I) (n=16, 6, 6, 8, 34)
    -0.75 ( 5.508 )
    -0.83 ( 1.941 )
    0.67 ( 4.885 )
    2.00 ( 4.408 )
    1.12 ( 4.879 )
        Change at Week 10 (Part I) (n=16, 5, 2, 6, 30)
    -0.69 ( 4.557 )
    -0.80 ( 2.168 )
    -1.00 ( 2.828 )
    0.00 ( 2.449 )
    0.17 ( 4.086 )
        Change at Week 15 (Part I) (n=7, 1, 1, 3, 15)
    -2.86 ( 6.176 )
    2.00 ( 99999 )
    6.00 ( 99999 )
    -1.00 ( 1.732 )
    1.00 ( 5.745 )
        Change at Week 5 (Part II) (n=18, 6, 6, 8, 34)
    0.06 ( 5.836 )
    -1.83 ( 2.639 )
    3.00 ( 4.940 )
    -0.03 ( 3.083 )
    -0.24 ( 4.068 )
        Change at Week 10 (Part II) (n=17, 5, 2, 6, 30)
    -0.35 ( 5.267 )
    -1.00 ( 1.225 )
    5.00 ( 1.414 )
    0.13 ( 2.428 )
    -0.43 ( 4.240 )
        Change at Week 15 (Part II) (n=8, 1, 1, 3, 15)
    -1.38 ( 4.779 )
    2.00 ( 99999 )
    8.00 ( 99999 )
    -2.42 ( 5.270 )
    1.47 ( 5.986 )
        Change at Week 5 (Part IV) (n=18, 6, 6, 8, 34)
    -1.50 ( 2.895 )
    -0.83 ( 2.401 )
    -0.50 ( 4.848 )
    0.25 ( 2.053 )
    -0.65 ( 2.806 )
        Change at Week 10 (Part IV) (n=17, 5, 2, 6, 30)
    -2.00 ( 2.318 )
    0.80 ( 1.304 )
    -3.00 ( 5.657 )
    0.00 ( 1.789 )
    -1.13 ( 3.530 )
        Change at Week 15 (Part IV) (n=8, 1, 1, 3, 15)
    -2.75 ( 2.493 )
    -2.00 ( 99999 )
    -7.00 ( 99999 )
    -1.33 ( 2.082 )
    -1.27 ( 2.404 )
        Change at Week 5 (Total) (n=16, 6, 6, 8, 34)
    -8.88 ( 12.832 )
    -10.00 ( 7.616 )
    5.33 ( 16.860 )
    2.34 ( 12.010 )
    -4.21 ( 18.216 )
        Change at Week 10 (Total) (n=16, 5, 2, 6, 30)
    -8.75 ( 10.951 )
    -3.60 ( 8.649 )
    6.50 ( 7.778 )
    0.13 ( 10.569 )
    -11.40 ( 18.448 )
        Change at Week 15 (Total) (n=7, 1, 1, 3, 15)
    -7.86 ( 12.456 )
    0.00 ( 99999 )
    13.00 ( 99999 )
    -9.08 ( 13.135 )
    0.73 ( 17.260 )
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Abnormalities Without Regard to Baseline Abnormality

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    End point title
    		 Number of Subjects With Laboratory Abnormalities Without Regard to Baseline Abnormality
    End point description
    The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed. Determination if there were any laboratory data abnormalities of potential clinical concern was based on Pfizer Data Standards. Incidence of laboratory test abnormalities (without regard to baseline abnormality) was summarized within each treatment group. Analysis population was Safety Analysis Set including all subjects who received at least 1 dose of PF-06649751 or placebo.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 17
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    23
    12
    15
    13
    44
    Units: Subjects
        Number of subjects with laboratory abnormalities
    19
    4
    9
    7
    25
    No statistical analyses for this end point

    Secondary: Number of Subjects With Vital Sign Results Meeting the Criteria for Categorical Summarization.

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    End point title
    		 Number of Subjects With Vital Sign Results Meeting the Criteria for Categorical Summarization.
    End point description
    Vital Signs including blood pressure and pulse rate were measured. Vital signs were collected first while the subject was in the supine position and then in the standing position. Analysis population was Safety Analysis Set including all subjects who received at least 1 dose of PF-06649751 or placebo.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 17
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    23
    13
    15
    13
    44
    Units: Subjects
        <90 mmHg (Supine Systolic Blood Pressure [SBP])
    1
    1
    2
    0
    3
        Max-Increase from Baseline >= 30 mmHg (Supine SBP)
    4
    1
    2
    1
    3
        Max-Decrease from Baseline >= 30 mmHg (Supine SBP)
    4
    1
    2
    2
    11
        <90 mmHg (Standing SBP)
    4
    1
    3
    2
    7
        Max-Increase from Baseline >=30mmHg (Standing SBP)
    4
    0
    3
    1
    3
        Max-Decrease from Baseline >=30mmHg (Standing SBP)
    3
    0
    3
    2
    12
        <50 mmHg (Supine Diastolic Blood Pressure [DBP])
    0
    0
    0
    1
    1
        Max-Increase from Baseline >=20 mmHg (Supine DBP)
    1
    0
    0
    1
    3
        Max-Decrease from Baseline >=20 mmHg (Supine DBP)
    1
    0
    2
    1
    13
        <50 mmHg (Standing DBP)|
    2
    0
    1
    2
    1
        Max-Increase from Baseline >=20mmHg (Standing DBP)
    3
    0
    2
    0
    1
        Max-Decrease from Baseline >=20mmHg (Standing DBP)
    5
    2
    3
    2
    17
        <40 beats per minute (bpm) (Supine Pulse Rate)
    0
    0
    0
    0
    0
        >120 bpm (Supine Pulse Rate)
    0
    0
    0
    0
    0
        <40 bpm (Standing Pulse Rate)
    0
    0
    0
    0
    0
        >140 bpm (Standing Pulse Rate)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization

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    End point title
    		 Number of Subjects with Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization
    End point description
    The average of the triplicate readings of ECG data was collected at each assessment time. Number of subjects with ECG results meeting the criteria for categorical summarization for time from the beginning of the P wave until the beginning of the QRS complex (PR Interval), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS Duration), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT Interval) and corrected QT (Fridericia correction) (QTcF Interval) were presented. Analysis population was Safety Analysis Set including all subjects who received at least 1 dose of PF-06649751 or placebo.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) to Week 17
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    23
    12
    15
    13
    44
    Units: Subjects
        >=300 msec (PR Interval)
    1
    0
    0
    0
    0
        Max-Increase From Baseline(%)>=25/50%(PR Interval)
    0
    0
    0
    0
    0
        >=140 msec (QRS Duration)
    0
    0
    0
    0
    0
        Max-Increase From Baseline(%)>=50% (QRS Duration)
    0
    0
    0
    0
    0
        >=500 msec (QT Interval)
    1
    0
    0
    0
    0
        450 - <480 msec (QTcF Interval)
    2
    0
    0
    0
    1
        480 - <500 msec (QTcF Interval)
    0
    0
    0
    0
    0
        >=500 msec (QTcF Interval)
    0
    0
    0
    0
    0
        Max-Increase From Baseline 30-<60 (QTcF Interval)
    1
    0
    0
    0
    1
        Max-Increase From Baseline >=60 (QTcF Interval)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits

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    End point title
    		 Number of Subjects With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits
    End point description
    The Columbia Suicide Severity Rating Scale (C-SSRS) was an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the C-CASA. There were 3 key endpoints for suicidality data analysis and evaluation:Suicidal Behavior: A subject was said to have suicidal behavior if the subject had experienced completed suicide/suicide attempt/reparatory acts toward imminent suicidal behavior;Suicidal Ideation: Any observed suicidal ideation mapped to a single C-CASA category;Suicidal Behavior or Ideation (subjects with new onset suicidality): A subject was considered to have a new onset of suicidality if the subject reported no ideation and no behavior at the baseline assessment and reported any behavior or ideation post-baseline. Safety Analysis Set included all subjects who received at least 1 dose of PF-06649751 or placebo. (n in the following table stands for number of subjects evaluable for each treatment arm)
    End point type
    Secondary
    End point timeframe
    Days 0 (Baseline), 7, 14, 21, 28, 35, 70, 77, 84, 91, 105 and 119
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    23
    13
    15
    13
    44
    Units: Subjects
        Baseline (n=23, 13, 15, 13 and 44)
    1
    0
    1
    0
    0
        Day 7 (n=22, 11, 14, 12 and 44)
    0
    0
    0
    0
    0
        Day 14 (n=19, 7, 10, 9 and 39)
    0
    0
    0
    0
    1
        Day 21 (n=21, 10, 10, 8 and 39)
    0
    0
    0
    0
    2
        Day 28 (n=19, 8, 9, 11 and 39)
    0
    0
    0
    0
    0
        Day 35 (n=21, 8, 7, 10 and 36)
    0
    0
    0
    0
    1
        Day 70 (n=20, 6, 7, 7 and 32)
    0
    0
    0
    0
    0
        Day 77 (n=6, 0, 0, 0 and 9)
    0
    0
    0
    0
    0
        Day 84 (n=7, 0, 0, 0 and 8)
    0
    0
    0
    0
    0
        Day 91 (n=6, 0, 0, 0 and 6)
    0
    0
    0
    0
    0
        Day 105 (n=17, 4, 3, 6 and 25)
    0
    0
    0
    1
    0
        Day 119 (n=15, 1, 0, 3 and 25)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders (ICDs) in Parkinson’s Disease – Rating Scale (QUIP-RS)

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    End point title
    		 Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders (ICDs) in Parkinson’s Disease – Rating Scale (QUIP-RS)
    End point description
    The QUIP-RS was a brief, patient reported outcome measure designed to assess the severity of symptoms of ICDs and related behaviors reported to occur in Parkinson’s disease. The QUIP-RS assesses 7 disorders (Gambling, Sex, Buying, Eating, Hobbyism-punding [performing tasks and repeating activities] and Taking medications), and the higher score indicated a greater level of the ICD. The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112. Safety Analysis Set included all subjects who received at least 1 dose of PF-06649751 or placebo. (n in the following table stands for number of subjects evaluable for each treatment arm)
    End point type
    Secondary
    End point timeframe
    Baseline (Day 0) and Weeks 5, 10 and 15
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    23
    13
    15
    13
    44
    Units: Scale
    arithmetic mean (standard deviation)
        Baseline (n=23, 13, 15, 13 and 44)
    17.1 ( 16.98 )
    9.0 ( 12.56 )
    9.0 ( 14.39 )
    12.5 ( 11.69 )
    6.8 ( 11.40 )
        Change at Week 5 (n=22, 11, 10, 12 and 42)
    -5.6 ( 11.37 )
    2.3 ( 10.05 )
    4.7 ( 9.58 )
    -5.4 ( 12.28 )
    0.5 ( 11.13 )
        Change at Week 10 (n=20, 5, 6, 6 and 30)
    -3.3 ( 12.16 )
    -1.8 ( 7.98 )
    -6.5 ( 9.63 )
    -5.8 ( 13.50 )
    1.0 ( 10.62 )
        Change at Week 15 (n=16, 4, 3, 4 and 24)
    -11.5 ( 16.29 )
    3.0 ( 10.30 )
    -3.3 ( 5.77 )
    -17.0 ( 11.34 )
    0.4 ( 5.91 )
    No statistical analyses for this end point

    Secondary: Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119

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    End point title
    		 Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119
    End point description
    The PWC-20 is a physician completed, 20 item reliable and sensitive instrument for the assessment of discontinuation symptoms. The PWC-20 was collected after the completion of study treatment and also at the first visit of follow-up. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60, and the higher score indicated more frequent/severe symptoms. Analysis population was Safety Analysis Set including all subjects who received at least 1 dose of PF-06649751 or placebo. (n in the following table stands for number of subjects evaluable for each treatment arm)
    End point type
    Secondary
    End point timeframe
    Days 105 and 119
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    23
    13
    15
    13
    44
    Units: Scale
    arithmetic mean (standard deviation)
        Day 105 (n=22, 12, 13, 13 and 40)
    3.5 ( 3.73 )
    5.6 ( 5.68 )
    5.8 ( 6.65 )
    8.2 ( 8.78 )
    7.1 ( 6.06 )
        Day 119 (n=15, 1, 0, 3 and 25)
    3.3 ( 3.08 )
    6.0 ( 99999 )
    99999 ( 99999 )
    7.7 ( 4.16 )
    5.8 ( 5.45 )
        Change From Day 105 to 119 (n=14, 1, 0, 3 and 24)
    -0.6 ( 3.08 )
    -11.0 ( 99999 )
    99999 ( 99999 )
    -1.7 ( 4.73 )
    -0.4 ( 4.79 )
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation due to AEs and Deaths

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    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation due to AEs and Deaths
    End point description
    An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event did not need necessarily to have a causal relationship with the treatment or usage. An SAE was any untoward medical occurrence at any dose that: • Resulted in death; • Was life threatening (immediate risk of death); • Required inpatient hospitalization or prolongation of existing hospitalization; • Resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); • Resulted in congenital anomaly/birth defect. Analysis population was Safety Analysis Set including all subjects who received at least 1 dose of PF-06649751 or placebo.
    End point type
    Secondary
    End point timeframe
    Day 1 to follow-up (Week 19 visit)
    End point values
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Number of subjects analysed
    23
    13
    15
    13
    44
    Units: Subjects
        AEs
    20
    7
    11
    10
    37
        SAEs
    1
    1
    0
    0
    2
        Discontinuation due to AEs
    3
    1
    3
    2
    9
        Death
    1
    0
    0
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 to follow-up (Week 19 visit)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 The subjects swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for subject's safety.

    Reporting group title
    PF-06649751 1 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject's safety.

    Reporting group title
    PF-06649751 3 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Reporting group title
    PF-06649751 7 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Reporting group title
    PF-06649751 15 mg QD
    Reporting group description
    		 The subjects swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for subject’s safety.

    Serious adverse events
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    2 / 44 (4.55%)
         number of deaths (all causes)
    1
    0
    0
    0
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Allergic oedema
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo PF-06649751 1 mg QD PF-06649751 3 mg QD PF-06649751 7 mg QD PF-06649751 15 mg QD
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 23 (65.22%)
    7 / 13 (53.85%)
    11 / 15 (73.33%)
    10 / 13 (76.92%)
    31 / 44 (70.45%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hot flush
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    0
    1
    1
    Hypertension
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    2 / 15 (13.33%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    1
    0
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    1
    0
    1
    Fatigue
         subjects affected / exposed
    3 / 23 (13.04%)
    1 / 13 (7.69%)
    2 / 15 (13.33%)
    2 / 13 (15.38%)
    1 / 44 (2.27%)
         occurrences all number
    3
    1
    2
    2
    1
    Malaise
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dysphonia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    1
    1
    1
    0
    4
    Aggression
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Anxiety
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    1
    0
    0
    0
    3
    Delusion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Depersonalisation/derealisation disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    0
    0
    1
    Depression
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    1
    1
    1
    Dysphemia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Hallucination
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Hypersexuality
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Insomnia
         subjects affected / exposed
    3 / 23 (13.04%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    2 / 44 (4.55%)
         occurrences all number
    3
    1
    0
    1
    2
    Irritability
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    4 / 44 (9.09%)
         occurrences all number
    0
    0
    0
    0
    4
    Rapid eye movement sleep behaviour disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Sleep disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    1
    1
    2
    Investigations
    Blood pressure decreased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Urine output decreased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Bone contusion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    2 / 13 (15.38%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    3
    0
    Fall
         subjects affected / exposed
    2 / 23 (8.70%)
    2 / 13 (15.38%)
    1 / 15 (6.67%)
    2 / 13 (15.38%)
    2 / 44 (4.55%)
         occurrences all number
    2
    2
    1
    2
    3
    Joint injury
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Laceration
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    0
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    0
    1
    1
    Cardiac disorders
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    1
    0
    1
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    2 / 13 (15.38%)
    4 / 44 (9.09%)
         occurrences all number
    0
    0
    1
    2
    4
    Dyskinesia
         subjects affected / exposed
    2 / 23 (8.70%)
    1 / 13 (7.69%)
    1 / 15 (6.67%)
    3 / 13 (23.08%)
    7 / 44 (15.91%)
         occurrences all number
    2
    2
    1
    3
    7
    Dystonia
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    3
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 13 (15.38%)
    1 / 15 (6.67%)
    3 / 13 (23.08%)
    11 / 44 (25.00%)
         occurrences all number
    0
    2
    1
    3
    14
    Memory impairment
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    0
    1
    1
    Myoclonus
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    1
    0
    1
    Parkinson's disease
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    1
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    1 / 44 (2.27%)
         occurrences all number
    1
    0
    0
    1
    1
    Diarrhoea
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    1 / 44 (2.27%)
         occurrences all number
    0
    0
    0
    1
    1
    Dysphagia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Flatulence
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    0
    0
    0
    0
    3
    Nausea
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 13 (15.38%)
    2 / 15 (13.33%)
    1 / 13 (7.69%)
    11 / 44 (25.00%)
         occurrences all number
    1
    2
    2
    1
    14
    Vomiting
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    1 / 15 (6.67%)
    0 / 13 (0.00%)
    2 / 44 (4.55%)
         occurrences all number
    0
    0
    1
    0
    2
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Flank pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    2
    0
    0
    1
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    0
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Posture abnormal
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Infections and infestations
    Asymptomatic bacteriuria
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Chronic sinusitis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 23 (13.04%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    0 / 13 (0.00%)
    0 / 44 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    Tooth abscess
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 13 (0.00%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    0 / 44 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 13 (7.69%)
    0 / 15 (0.00%)
    1 / 13 (7.69%)
    3 / 44 (6.82%)
         occurrences all number
    1
    1
    0
    1
    3

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Jul 2016
    • Clarified that primary and secondary endpoints were measured in ON and OFF “hours”; • Added “Daily ON Time with troublesome dyskinesia (hours)” as a secondary endpoint; • Clarified that secondary endpoints were measured as change from baseline; • Added cognition as an exploratory objective; • Added SDMT as an exploratory endpoint for cognition; • Added electronic Parkinson’s disease Activity of Daily Living and Improvement (ADL&I) Scale as an optional exploratory sub study in a subset of subjects (US sites only).
    22 Nov 2016
    • Removed “reduction of L-Dopa dose” from the secondary objectives; • Removed secondary endpoints related to daily L-Dopa dose; • L-Dopa reduction was no longer required during Period B and daily L-Dopa dose and frequency should remain stable over the entire course of the study (except in the case of unacceptable dopaminergic AEs); • Required clinic visits and corresponding MDS-UPDRS III deleted at Week 2, Week 3, Week 11, Week 12 and Week 13; • Added the open-label extension study.
    17 Jul 2017
    France only: The protocol underwent a country-specific amendment at the request of the France Regulatory Authorities to include guidance for the eye examination.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated prematurely due to insufficient efficacy and not due to safety reasons.
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