Back to resultsEfficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients at Early Stage of the Disease
Primary Purpose
Parkinson Disease
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
PF-06649751
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring Early Parkinson Disease, Phase 2
Eligibility Criteria
Inclusion Criteria:
- Females of non-childbearing potential and/or male subjects
- Clinical diagnosis of Parkinson's disease.
- Parkinson's Disease Hoehn & Yahr Stage I-III inclusive
- Treatment naïve or history of prior incidental treatment with dopaminergic agents for no more than 28 days
- Able to refrain from any Parkinson's disease medication not permitted by the protocol.
Exclusion Criteria:
- History or presence of atypical Parkinsonian syndrome.
- Severe acute or chronic medical or psychiatric condition or cognitive impairment or laboratory abnormality.
- Any condition possibly affecting drug absorption.
- Participation in other studies involving investigational drug(s), or treatment with any investigational drug within 30 days.
Sites / Locations
- St Joseph's Hospital and Medical Center, Barrow Neurology Clinics
- St. Joseph's Hospital and Medical Center
- Parkinson's Disease and Movement Disorders Center of Boca Raton
- University of Miami
- University of South Florida Carol and Frank Morsani Center for Advanced Health Care
- University of South Florida Faculty Office Building
- University of South Florida
- University of South Florida Parkinson's Disease and Movement Disorders Center
- Atlanta Center for Medical Research
- Rush University Medical Center
- University of Kansas Medical Center
- Massachusetts General Hospital
- Brigham and Women's Hospital
- Asheville Neurology Specialists PA
- Cleveland Clinic
- University of Toledo, Gardner-McMaster Parkinson Center
- University of Toledo
- AS Clinical Research Consultants of North Texas, PLLC
- Baylor College of Medicine
- Sentara Neurology Specialists
- Hôpital Henri Mondor
- Hopital Henri Mondor
- CHU de Grenoble Alpes
- CHU Grenoble Alpes
- Hospital de La Timone
- Hospital La Timone
- Hopital Pitie Salpetriere
- Hopital Pitie-Salpetriere
- St. Josef Hospital GmbH
- Praxis Oehlwein Outpatient clinic for PD, DBS, Movement Disorders
- Klinik Haag i. OB
- Paracelsus-Elena-Klinik Kassel
- Universitätsklinikum Gießen und Marburg GmbH
- University hospital Tuebingen
- Universitaetsklinik Ulm
- Edith Wolfson Medical Center
- Pharmacy, Edith Wolfson Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
PF-06649751
Arm Description
Outcomes
Primary Outcome Measures
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score at Week 15
MDS-UPDRS Part III was used to assess the motor signs of Parkinson's disease. It was comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question was anchored with 5 responses that were linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The MDS-UPDRS Part III total score range is 0-132. Higher score indicates more severe motor signs of Parkinson's disease. A negative change from baseline represents an improvement in motor function.
Secondary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Following safety laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes); chemistry (blood urea nitrogen/urea and creatinine, glucose , calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urine bilirubin, urobilinogen, urine creatinine, microscopy, and specific gravity).
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria
Vital signs categorical summarization criteria: 1) supine and standing systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine and standing diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) standing pulse rate <40 or >140 bpm; 5) maximum change from baseline (increase or decrease) in supine and standing DBP greater than or equal to (>=) 20 mmHg; 6) maximum change from baseline (increase or decrease) in supine and standing SBP >=30 mmHg. Orthostatic hypotension criterion was defined as a decrease of >=20 mmHg for SBP or >=10 mmHg for DBP 2 minutes after standing from a supine position.
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters
ECG categorical summarization criteria: 1) QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): >=140 milliseconds (msec), >=50% increase from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 4) QTcF interval (QT corrected for heart rate using Fridericia's formula): absolute value of 450 to <480 msec, 480 to <500 msec, >=500 msec; an increase from baseline of 30 to <60 msec or >=60 msec.
Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Participants with new onset suicidality were those without suicidal ideation and behavior at baseline and reported any suicidal behavior or ideation post-baseline as assessed by C-CASA code mapped from C-SSRS data. Participants with worsening suicidality were those who moved to a lower numbered C-CASA category than was reported at baseline.
Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105
The QUIP-RS has 4 primary questions pertaining to commonly reported thoughts, urges/desires, and behaviors associated with impulsive-compulsive disorder , each applied to the 4 impulsive-compulsive disorders (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). Each question is anchored with the following 5 responses: Never (0), Rarely (1), Sometimes (2), Often (3), and Very Often (4). The scoring range for each item (ie, disorder) is 0-16. The QUIP-RS total score range is 0-64. Higher score indicates a greater level of the impulsive compulsive disorder.
Total Physician Withdrawal Checklist (PWC-20) Score
The PWC-20 is a 20-item reliable and sensitive instrument for the assessment of benzodiazepine-like discontinuation symptoms. The total PWC-20 score is the sum of 20 item scores and ranges between 0 and 60. The higher score indicates more frequent/severe symptoms.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02847650
Brief Title
Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients at Early Stage of the Disease
Official Title
A 15-WEEK, PHASE 2, DOUBLE BLIND, RANDOMIZED, PLACEBO-CONTROLLED, FLEXIBLE DOSE STUDY TO INVESTIGATE THE EFFICACY, SAFETY AND TOLERABILITY OF PF-06649751 IN SUBJECTS WITH EARLY STAGE PARKINSON'S DISEASE
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
Study B7601011 was terminated on 29 Jan 2018 due to lack of efficacy in moderate/advanced Parkinson's disease.
Study Start Date
October 17, 2016 (Actual)
Primary Completion Date
January 29, 2018 (Actual)
Study Completion Date
January 29, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of PF-06649751 in Parkinson's disease patients at early stage of the disease.
Detailed Description
The B7601011 study has a randomized, double-blind, placebo-controlled parallel group design. Approximately 88 subjects will be randomized to 2 treatment groups. Each subject will participate in the study for approximately 23 weeks including a 30 day screening period, 15 week double blind treatment period, and an approximately 28 day follow-up period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
Early Parkinson Disease, Phase 2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
57 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
PF-06649751
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
oral tablet once daily
Intervention Type
Drug
Intervention Name(s)
PF-06649751
Other Intervention Name(s)
flexible dose oral tablet once daily
Primary Outcome Measure Information:
Title
Change From Baseline in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Total Score at Week 15
Description
MDS-UPDRS Part III was used to assess the motor signs of Parkinson's disease. It was comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question was anchored with 5 responses that were linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The MDS-UPDRS Part III total score range is 0-132. Higher score indicates more severe motor signs of Parkinson's disease. A negative change from baseline represents an improvement in motor function.
Time Frame
Baseline (Day -1/randomization), Week 15
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Time Frame
From first dose of study treatment up to 28 days after last dose (up to Day 133)
Title
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Description
Following safety laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes); chemistry (blood urea nitrogen/urea and creatinine, glucose , calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urine bilirubin, urobilinogen, urine creatinine, microscopy, and specific gravity).
Time Frame
Baseline (Day -1/randomization) up to Day 119 follow-up visit
Title
Number of Participants With Vital Signs Data Meeting Categorical Summarization and Orthostatic Hypotension Criteria
Description
Vital signs categorical summarization criteria: 1) supine and standing systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine and standing diastolic blood pressure (DBP) <50 mmHg; 3) supine pulse rate <40 or >120 beats per minute (bpm); 4) standing pulse rate <40 or >140 bpm; 5) maximum change from baseline (increase or decrease) in supine and standing DBP greater than or equal to (>=) 20 mmHg; 6) maximum change from baseline (increase or decrease) in supine and standing SBP >=30 mmHg. Orthostatic hypotension criterion was defined as a decrease of >=20 mmHg for SBP or >=10 mmHg for DBP 2 minutes after standing from a supine position.
Time Frame
Baseline (Day -1/randomization) up to Day 119 follow-up visit
Title
Number of Participants Meeting the Categorical Summarization Criteria for Electrocardiogram (ECG) Parameters
Description
ECG categorical summarization criteria: 1) QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): >=140 milliseconds (msec), >=50% increase from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec; 3) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 4) QTcF interval (QT corrected for heart rate using Fridericia's formula): absolute value of 450 to <480 msec, 480 to <500 msec, >=500 msec; an increase from baseline of 30 to <60 msec or >=60 msec.
Time Frame
Baseline (Day -1/randomization) up to Day 119 follow-up visit
Title
Number of Participants With Worsening and New Onset Suicidality as Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
Description
The C-SSRS is an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Participants with new onset suicidality were those without suicidal ideation and behavior at baseline and reported any suicidal behavior or ideation post-baseline as assessed by C-CASA code mapped from C-SSRS data. Participants with worsening suicidality were those who moved to a lower numbered C-CASA category than was reported at baseline.
Time Frame
Baseline (Day -1/randomization) up to Day 119 follow-up visit
Title
Change From Baseline in Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) Total Score at Days 35, 63, and 105
Description
The QUIP-RS has 4 primary questions pertaining to commonly reported thoughts, urges/desires, and behaviors associated with impulsive-compulsive disorder , each applied to the 4 impulsive-compulsive disorders (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). Each question is anchored with the following 5 responses: Never (0), Rarely (1), Sometimes (2), Often (3), and Very Often (4). The scoring range for each item (ie, disorder) is 0-16. The QUIP-RS total score range is 0-64. Higher score indicates a greater level of the impulsive compulsive disorder.
Time Frame
Baseline (Day -1 or randomization); Days 35, 63, 105
Title
Total Physician Withdrawal Checklist (PWC-20) Score
Description
The PWC-20 is a 20-item reliable and sensitive instrument for the assessment of benzodiazepine-like discontinuation symptoms. The total PWC-20 score is the sum of 20 item scores and ranges between 0 and 60. The higher score indicates more frequent/severe symptoms.
Time Frame
Day 119
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Females of non-childbearing potential and/or male subjects
Clinical diagnosis of Parkinson's disease.
Parkinson's Disease Hoehn & Yahr Stage I-III inclusive
Treatment naïve or history of prior incidental treatment with dopaminergic agents for no more than 28 days
Able to refrain from any Parkinson's disease medication not permitted by the protocol.
Exclusion Criteria:
History or presence of atypical Parkinsonian syndrome.
Severe acute or chronic medical or psychiatric condition or cognitive impairment or laboratory abnormality.
Any condition possibly affecting drug absorption.
Participation in other studies involving investigational drug(s), or treatment with any investigational drug within 30 days.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
St Joseph's Hospital and Medical Center, Barrow Neurology Clinics
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
St. Joseph's Hospital and Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Parkinson's Disease and Movement Disorders Center of Boca Raton
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of South Florida Carol and Frank Morsani Center for Advanced Health Care
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of South Florida Faculty Office Building
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
University of South Florida Parkinson's Disease and Movement Disorders Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Atlanta Center for Medical Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30331
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Asheville Neurology Specialists PA
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28806
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Toledo, Gardner-McMaster Parkinson Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
University of Toledo
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
AS Clinical Research Consultants of North Texas, PLLC
City
Greenville
State/Province
Texas
ZIP/Postal Code
75401
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Sentara Neurology Specialists
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23456
Country
United States
Facility Name
Hôpital Henri Mondor
City
CRÉTEIL Cedex
ZIP/Postal Code
94010
Country
France
Facility Name
Hopital Henri Mondor
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
CHU de Grenoble Alpes
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CHU Grenoble Alpes
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
Hospital de La Timone
City
Marseille
ZIP/Postal Code
13385 Cedex 05
Country
France
Facility Name
Hospital La Timone
City
Marseille
ZIP/Postal Code
13385 cedex 05
Country
France
Facility Name
Hopital Pitie Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hopital Pitie-Salpetriere
City
Paris
ZIP/Postal Code
75651 cedex 13
Country
France
Facility Name
St. Josef Hospital GmbH
City
Bochum
State/Province
Nordrhein-westfalen
ZIP/Postal Code
44791
Country
Germany
Facility Name
Praxis Oehlwein Outpatient clinic for PD, DBS, Movement Disorders
City
Gera
ZIP/Postal Code
07551
Country
Germany
Facility Name
Klinik Haag i. OB
City
Haag I. OB
ZIP/Postal Code
83527
Country
Germany
Facility Name
Paracelsus-Elena-Klinik Kassel
City
Kassel
ZIP/Postal Code
34128
Country
Germany
Facility Name
Universitätsklinikum Gießen und Marburg GmbH
City
Marburg
ZIP/Postal Code
35043
Country
Germany
Facility Name
University hospital Tuebingen
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Universitaetsklinik Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Edith Wolfson Medical Center
City
Holon
ZIP/Postal Code
58100
Country
Israel
Facility Name
Pharmacy, Edith Wolfson Medical Center
City
Holon
ZIP/Postal Code
58100
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
32201505
Citation
Riesenberg R, Werth J, Zhang Y, Duvvuri S, Gray D. PF-06649751 efficacy and safety in early Parkinson's disease: a randomized, placebo-controlled trial. Ther Adv Neurol Disord. 2020 Mar 6;13:1756286420911296. doi: 10.1177/1756286420911296. eCollection 2020.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=B7601011
Description
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Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients at Early Stage of the Disease
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