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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 : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Placebo Drug: PF-06649751 low dose (1 mg QD) Drug: PF-06649751 middle dose 1 (3 mg QD) Drug: PF-06649751 middle dose 2 (7 mg QD) Drug: PF-06649751 high dose (15 mg QD) Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 3, 2016
Actual Primary Completion Date : November 10, 2017
Actual Study Completion Date : November 10, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

Experimental: PF-06649751 low dose (1 mg QD)
PF-06649751 low dose level (1 mg QD)
Drug: PF-06649751 low dose (1 mg QD)
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)
Drug: PF-06649751 middle dose 1 (3 mg QD)
PF-06649751 lower middle dose 1 (3 mg QD)

Experimental: PF-06649751 middle dose 2 (7 mg QD)
PF-06649751 higher middle dose 2 (7 mg QD)
Drug: PF-06649751 middle dose 2 (7 mg QD)
PF-06649751higher middle dose 2 (7 mg QD)

Experimental: PF-06649751 high dose (15 mg QD)
PF-06649751 high dose (15 mg QD)
Drug: PF-06649751 high dose (15 mg QD)
PF-06649751 high dose (15 mg QD)




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. 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.


  4. 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.


  5. 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

  6. 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.


  7. 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.

  8. 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.


  9. 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.

  10. 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.


  11. 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.


  12. 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.



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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02687542


  Show 57 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Statistical Analysis Plan  [PDF] September 13, 2017
Study Protocol  [PDF] November 22, 2016


Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02687542     History of Changes
Other Study ID Numbers: B7601003
2015-004912-39 ( EudraCT Number )
A-ROSE PD ( Other Identifier: Alias Study Number )
A-ROSE ( Other Identifier: Alias Study Number )
First Posted: February 22, 2016    Key Record Dates
Results First Posted: December 24, 2018
Last Update Posted: December 24, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
Parkinson Disease
Motor Fluctuation

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases