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Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients With Motor Fluctuations

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ClinicalTrials.gov Identifier: NCT02687542
Recruitment Status : Terminated (Terminated 25Sep17 due to insufficient efficacy. Not due to safety reasons.)
First Posted : February 22, 2016
Results First Posted : December 24, 2018
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 29, 2016
First Posted Date  ICMJE February 22, 2016
Results First Submitted Date  ICMJE October 30, 2018
Results First Posted Date  ICMJE December 24, 2018
Last Update Posted Date November 23, 2020
Actual Study Start Date  ICMJE March 3, 2016
Actual Primary Completion Date November 10, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
Change From Baseline in Daily OFF Time at Week 10 [ Time Frame: Week 10; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0). ]
A paper Hauser diary was utilized to record motor state for half-hour intervals. Participants 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
Change from baseline in daily OFF time [ Time Frame: Week 10. The baseline will be Day 0 (Randomization). ]
Change from baseline in daily OFF time based on patient reported Hauser diary
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2018)
  • Change From Baseline in Daily OFF Time [ Time Frame: Weeks 3, 5, 10 and 15; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0). ]
    A paper Hauser diary was utilized to record motor state for half hour intervals. Participants 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. Results at Week 15 should be interpreted with caution given almost half the participants 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.
  • Change From Baseline in Daily ON Time With Troublesome Dyskinesia [ Time Frame: Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time with Troublesome Dyskinesia (using 3 Hauser patient diary Days) prior to Day -1 (study derived day and equalled to nominal visit Day 0). ]
    A paper Hauser diary was utilized to record motor state for half hour intervals. The participants 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, participants 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. Results at Week 15 should be interpreted with caution given almost half the participants 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.
  • Change From Baseline in Daily ON Time Without Troublesome Dyskinesia [ Time Frame: Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time without Troublesome Dyskinesia (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit Day 0) ]
    A paper Hauser diary was utilized to record motor state for half hour intervals. The participants 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, participants 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. Results at Week 15 should be interpreted with caution given almost half the participants 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.
  • Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III [ Time Frame: 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 ]
    MDS-UPDRS Part III assessed the motor signs of Parkinson's disease and was administered by the investigator. 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. If more than 7 of the Part III items were missing, the score for that time point was missing, otherwise MDS-UPDRS Part III score was imputed as sum of the non-missing items*(total number of items)/ (number of items non-missing). The MDS-UPDRS Part III total score range is 0-132. Higher score indicated more severe motor signs of Parkinson's disease. Results at Week 15 should be interpreted with caution given almost half the participants 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.
  • Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score [ Time Frame: Weeks 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement ]
    Each question of Part I,II or IV with 5 responses was linked to the same clinical terms as Part III.The score was missing if more than 7 items were missing for a time point; otherwise Part I,II or IV score was imputed as sum of non-missing items*(total number of items)/(number of items non-missing).•PartI (Non-Motor Aspects of Experiences of Daily Living) assessed non-motor experiences of daily living using 13questions(Range:0-52).•PartII(Motor Aspects of Experiences of Daily Living) assessed motor experiences of daily living using 13questions(Range:0-52).•PartIV(Motor Complications) assessed motor complications,dyskinesias, and motor fluctuations using historical and objective information with 6questions(Range:0-24).•MDS-UPDRS Total Score:the sum of Parts I,II,III,and IV(Range:0-260).Higher score indicated more severe motor signs of Parkinson's disease.Week15's results were interpreted cautiously given almost half participants were not available for the analysis as compared to Week10
  • Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality [ Time Frame: Baseline (Day 0) to Week 17 ]
    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.
  • Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization [ Time Frame: Baseline (Day 0) to Week 17 ]
    Vital Signs including blood pressure and pulse rate were measured. Vital signs were collected first while the participant was in the supine position and then in the standing position.
  • Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization [ Time Frame: Baseline (Day 0) to Week 17 ]
    The average of the triplicate readings of ECG data was collected at each assessment time. Number of participants 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.
  • Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits [ Time Frame: Days 0 (Baseline), 7, 14, 21, 28, 35, 70, 77, 84, 91, 105 and 119 ]
    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 participant was said to have suicidal behavior if the participant 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 (participants with new onset suicidality): A participant was considered to have a new onset of suicidality if the participant reported no ideation and no behavior at the baseline assessment and reported any behavior or ideation post-baseline. Data observed at screening was not considered in the definition of worsening.
  • Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) [ Time Frame: Baseline (Day 0) and Weeks 5, 10 and 15 ]
    The QUIP-RS was a brief, patient reported outcome measure designed to assess the severity of symptoms of Impulsive-Compulsive Disorders (ICDs) and related behaviors reported to occur in Parkinson's disease. The QUIP-RS assessed 7 disorders (Gambling, Sex, Buying, Eating, Hobbyism-punding [performing tasks and repeating activities] and Taking medications). If more than 5 items were missing, the total QUIP-RS score was set as missing; otherwise, the total QUIP-RS score was imputed as follows: sum of the non-missing item scores * (total number of items) / (number of items non-missing). 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.
  • Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119 [ Time Frame: Days 105 and 119 ]
    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. If more than 5 items were missing, the total PWC-20 score was missing; otherwise, the total PWC-20 score was imputed as follows: sum of the non-missing items * (total number of items) / (number of items non-missing). The higher score indicated more frequent/severe symptoms.
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs and Deaths [ Time Frame: Day 1 to follow-up (Week 19 visit) ]
    An AE was any untoward medical occurrence in a clinical investigation participant 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 16, 2016)
  • % reduction in total daily L-Dopa dose [ Time Frame: Weeks 10 and 15. The baseline will be Day 0 (Randomization). ]
    % reduction in total daily L-Dopa dose from pre-study baseline
  • Number of subjects with >=25, 50%, 75% and with 100% reduction in daily L-Dopa dose [ Time Frame: Weeks 10 and 15. The baseline will be Day 0 (Randomization). ]
    Number of subjects with >=25%, 50%, 75% and with 100% reduction from pre-study baseline in daily L-Dopa dose
  • Safety and Tolerability including AEs, Clinical laboratory, Vital signs, and ECG. [ Time Frame: From Randomization to Week 15 ]
  • Columbia Suicide Severity Rating Scale (C-SSRS) at end of treatment. [ Time Frame: From Randomization to Week 15 ]
    C-SSRS assessed whether participant experienced following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has subject engaged in non-suicidal self-injurious behavior")
  • Daily OFF time [ Time Frame: From Randomization to Week 15 ]
    Change from baseline in daily OFF time based on patient reported Hauser diary
  • Daily ON time without troublesome dyskinesia [ Time Frame: From Randomization to Week 15 ]
    Change from baseline in daily ON time without troublesome dyskinesia based on patient reported Hauser diary
  • MDS - UPDRS Part III [ Time Frame: From Randomization to Week 15 ]
    Based on Movement Disorder Society - Unified Parkinson's Disease Rating Scale.
  • MDS-UPDRS Parts I, II, IV, and total score [ Time Frame: From Randomization to Week 15 ]
    Based on Movement Disorder Society - Unified Parkinson's Disease Rating Scale
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients With Motor Fluctuations
Official Title  ICMJE 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
Brief Summary The purpose of this study is to evaluate the efficacy, safety and tolerability of PF-06649751 in Parkinson's disease patients who experience motor-fluctuations.
Detailed Description The study has a randomized, double-blind, placebo-controlled parallel group design. Approximately 198 subjects will be randomized to 5 treatment groups. Each subject will participate in the study for approximately 23 weeks including a 30 day screening period, 15 week double blind treatment period, and an approximately 28 day follow-up period.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Parkinson Disease
Intervention  ICMJE
  • Drug: Placebo
    Placebo
  • Drug: PF-06649751 low dose (1 mg QD)
    PF-06649751 low dose (1 mg QD)
  • Drug: PF-06649751 middle dose 1 (3 mg QD)
    PF-06649751 lower middle dose 1 (3 mg QD)
  • Drug: PF-06649751 middle dose 2 (7 mg QD)
    PF-06649751higher middle dose 2 (7 mg QD)
  • Drug: PF-06649751 high dose (15 mg QD)
    PF-06649751 high dose (15 mg QD)
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
  • Experimental: PF-06649751 low dose (1 mg QD)
    PF-06649751 low dose level (1 mg QD)
    Intervention: Drug: PF-06649751 low dose (1 mg QD)
  • Experimental: PF-06649751 middle dose 1 (3 mg QD)
    PF-06649751 lower middle dose 1 (3 mg QD)
    Intervention: Drug: PF-06649751 middle dose 1 (3 mg QD)
  • Experimental: PF-06649751 middle dose 2 (7 mg QD)
    PF-06649751 higher middle dose 2 (7 mg QD)
    Intervention: Drug: PF-06649751 middle dose 2 (7 mg QD)
  • Experimental: PF-06649751 high dose (15 mg QD)
    PF-06649751 high dose (15 mg QD)
    Intervention: Drug: PF-06649751 high dose (15 mg QD)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 20, 2017)
108
Original Estimated Enrollment  ICMJE
 (submitted: February 16, 2016)
198
Actual Study Completion Date  ICMJE November 10, 2017
Actual Primary Completion Date November 10, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Females of non-childbearing potential and/or male subjects between the ages of 40 and 85 years, inclusive.
  • Clinical diagnosis of Parkinson's disease.
  • Able to refrain from any Parkinson's disease medication not permitted by the protocol.

Exclusion Criteria:

  • Female of childbearing potential
  • History or presence of atypical Parkinsonian syndrome.
  • History of surgical intervention for Parkinson's disease.
  • Severe acute or chronic medical or psychiatric condition or laboratory abnormality.
  • Any condition possibly affecting drug absorption.
  • Participation in other studies involving investigational drug(s), or treatment with any investigational drug within 30 days.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Germany,   Japan,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02687542
Other Study ID Numbers  ICMJE B7601003
2015-004912-39 ( EudraCT Number )
A-ROSE PD ( Other Identifier: Alias Study Number )
A-ROSE ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP