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Study Evaluating The Safety, Tolerability And Brain Function Of 2 Doses Of PF-0254920 In Subjects With Early Huntington's Disease

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ClinicalTrials.gov Identifier: NCT01806896
Recruitment Status : Completed
First Posted : March 7, 2013
Results First Posted : December 14, 2017
Last Update Posted : December 14, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE March 6, 2013
First Posted Date  ICMJE March 7, 2013
Results First Submitted Date  ICMJE July 11, 2016
Results First Posted Date  ICMJE December 14, 2017
Last Update Posted Date December 14, 2017
Study Start Date  ICMJE September 2013
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2017)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 38 ]
    An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of treatment and up to the follow-up period that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-serious AEs.
  • Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern (Without Regard to Baseline Abnormality) [ Time Frame: Baseline up to Day 38 ]
    The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total and direct bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein/albumin, hemoglobin/blood, ketones/acetone, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (urine/serum pregnancy test, glycosylated hemoglobin [HbA1c, if diabetic]).
  • Number of Participants With Potentially Clinically Significant Vital Signs Findings [ Time Frame: Baseline up to Day 38 ]
    Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate less than (<)40 or greater than (>)120 beats per minute (bpm), standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of greater than or equal to (>=)30 millimeters of mercury (mmHg) change from baseline or SBP <90 mmHg, diastolic blood pressure (DBP) >=20 mmHg change from baseline or DBP <50 mmHg.
  • Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Baseline up to Day 38 ]
    ECG parameters included PR interval, QRS complex, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval ≥200 milliseconds (msec) or ≥25% increase when baseline is >100 msec; QRS interval ≥50% increase from baseline when baseline is less than or equal to (<=)200 msec; and QTcF ≥450 msec or ≥30 msec increase from baseline.
  • Number of Participants With Change From Baseline in Body Weight of >=7% [ Time Frame: Baseline up to Day 38 ]
    Weight assessment was performed by a study physician or a trained study nurse and was included in the physical examination.
  • Categorical Summary of Participants Meeting Stopping Criteria [ Time Frame: Baseline up to Day 38 ]
    Absolute neutrophil count (ANC) and WBC were monitored for safety. Participants with WBC <3000 but >=2000 cells/mm^3 or ANC <1500 but >=1000 cells/mm^3 were to have study treatment suspended. Participants with WBC <2000 or ANC <1000 cells/mm^3 were to be discontinued from study participation.
  • Change From Baseline in Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score at Day 28 [ Time Frame: Baseline, Day 28 ]
    The UHDRS is a clinical rating scale to provide a uniform assessment of the clinical features and course of Huntington Disease. The Total Motor Score (TMS) is 1 of the 6 components of UHDRS, includes 31 items, and ranges from a scale of 0 to 124 (higher scores indicate more severe disease).
  • Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Baseline [ Time Frame: Baseline (Day 1) ]
    C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts towards imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.
  • Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 7 [ Time Frame: Day 7 ]
    C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.
  • Number of Participants With Suicidal Tendencies (C-SSRS Mapped to C-CASA) at Day 28 [ Time Frame: Day 28 ]
    C-SSRS is a participant rated questionnaire to assess suicidal ideation, suicidal behavior, actual attempts (yes or no responses), and intensity of ideation (rated 1=low severity to 5=high severity). Yes/No responses are mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. A participant could have a yes or no response in more than 1 category.
Original Primary Outcome Measures  ICMJE
 (submitted: March 6, 2013)
Change from Baseline to Day 28 of Unified Huntington Disease Rating Scale -Total Motor Score (TMS) [ Time Frame: Screening, Day 1, Day 28 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2017)
  • Change From Baseline in Functional Magnetic Resonance Imaging (fMRI) in Monetary Incentive Delay (MID) Task at Day 28 [ Time Frame: Baseline (Day 1), Day 28 ]
    The monetary incentive delay (MID) task is established as a reliable method to elicit ventral striatal (VS) activity in relation to reward/punishment anticipation and tracked with dysfunctionalities across a range of conditions in which incentive motivation is thought to be abnormal (schizophrenia, depression, substance abuse, and pathological gambling). Pharmacological intervention has demonstrated reversal of observed deficit. The beta contrast value of 'REW' is for analysis of reward-related activity in VS within the task-related 'reward network' during the gain condition (relative to neutral) of the MID task. The changes in beta contrasts (fMRI) provided are changes in parameter estimates and do not have a unit of measure.
  • Change From Baseline in Grip Strength Incentive Motivation Task at Day 28: Percent of Maximum Voluntary Contraction (MVC) [ Time Frame: Baseline, Day 28 ]
    This incentive force task was developed to independently dissociate the degree to which a participant responds to reward motivation versus emotional motivation. The task itself included 12 repetitions of 9 trial types, for a total of 108 trials, grouped in a single session lasting about 20 minutes. The trial types were generated according to a combination of 3 emotional categories (negative, neutral, and positive pictures presented) and to 3 monetary incentives (0.01, 0.1, and 1€). Emotional categories and monetary incentives were randomly distributed over the trials and the sequence was fixed such that all subjects were assessed on the exact same task. For each trial, the subject was first presented with an emotional picture displayed on screen for 3000 milliseconds (ms).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2013)
  • Change from Baseline to Day28 in fMRI parameter estimates and percent signal change during Monetary Incentive Delay [ Time Frame: Baseline, Day28 ]
  • Change from Baseline to Day28 in Grip Strength Incentive Motivation task score [ Time Frame: Baseline predose, Baseline postdose, Day28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating The Safety, Tolerability And Brain Function Of 2 Doses Of PF-0254920 In Subjects With Early Huntington's Disease
Official Title  ICMJE A Phase 2, Double-blind Randomized, Sequential Treatment Group, Placebo-controlled Study To Evaluate The Safety, Tolerability And Brain Cortico-striatal Function Of 2 Doses Of Pf-02545920 In Subjects With Early Huntington's Disease
Brief Summary This study will evaluate the Safety, Tolerability and Brain Function of 2 doses of PF-0254920 in Subjects with Early Huntington's Disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Huntington's Disease
Intervention  ICMJE
  • Drug: PF-02545920
    • Dose will be titrated up every 2 days by 5mg increments: 5mg Days 1-2, 10mg days 3-4, 15mg days 5-6, and reach 20 mg from Days 7 to Day28.
    • Orally, approx. Q12H (range 10-14 hours), administered at least one hour prior to, or two hours after meals.
    • Treatment for 28 days.
  • Drug: Placebo

    - Orally, approx. Q12H (range 10-14 hours), administered at least one hour prior to, or two hours after meals.

    Dosing for 28 days.

  • Drug: PF-02545920
    • 5mg dose
    • Orally, approx. Q12H (range 10-14 hours), administered at least one hour prior to, or two hours after meals.
    • Dosing for 28 days.
  • Drug: Placebo
    • Orally, approx. Q12H (range 10-14 hours), administered at least one hour prior to, or two hours after meals.
    • Dosing for 28 days.
Study Arms  ICMJE
  • Experimental: 20 mg Arm Cohort A
    Intervention: Drug: PF-02545920
  • Placebo Comparator: Placebo Arm Cohort A
    Intervention: Drug: Placebo
  • Experimental: 5 mg Arm Cohort B
    Intervention: Drug: PF-02545920
  • Placebo Comparator: Placebo Arm Cohort B
    Intervention: Drug: Placebo
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 Completed
Actual Enrollment  ICMJE
 (submitted: February 17, 2015)
37
Original Estimated Enrollment  ICMJE
 (submitted: March 6, 2013)
65
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must have a diagnosis of Huntington's Disease
  • a CAG repeat expansion equal or great than 39
  • a Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score equal or greater than 5 and less than 60
  • a UHDRS Total Functional Capacity equal or greater than 9

Exclusion Criteria:

  • Subjects with evidence or history of severe acute or chronic medical condition or laboratory abnormality, or significant neurological disorder other than HD.
  • Treatment with any antipsychotic medication within 5 weeks of enrollment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 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 France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01806896
Other Study ID Numbers  ICMJE A8241016
2012-004432-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
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 May 2017

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