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Open Label Extension Study To Investigate Long Term Safety, Tolerability And Efficacy Of Pf-02545920 In Subjects With Huntington's Disease Who Completed Study A8241021

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ClinicalTrials.gov Identifier: NCT02342548
Recruitment Status : Terminated (Study terminated on 15DEC2016 due to study A8241021 showing no significant difference on primary endpoint between PF-02545920 & placebo. No safety concerns.)
First Posted : January 21, 2015
Results First Posted : April 23, 2018
Last Update Posted : April 23, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 15, 2015
First Posted Date  ICMJE January 21, 2015
Results First Submitted Date  ICMJE February 2, 2018
Results First Posted Date  ICMJE April 23, 2018
Last Update Posted Date April 23, 2018
Actual Study Start Date  ICMJE February 25, 2015
Actual Primary Completion Date February 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 23, 2018)
  • Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events [ Time Frame: 1 year ]
    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study treatment and up to 28 calendar days after the last administration of study treatment that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs.
  • Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) [ Time Frame: 1 year ]
    The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, eosinophils, monocytes, basophils, and lymphocytes), chemistry (blood urea nitrogen/urea, creatinine, glucose, glycosylated hemoglobin [diabetics only], calcium, phosphorus, magnesium, creatine kinase, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (color, appearance, specific gravity, pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, and microscopy), and other tests (follicle stimulating hormone, urine drug screen, urine pregnancy [human chorionic gonadotropin, hCG], serum beta hCG). Abnormality was determined by the investigator.
  • Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria [ Time Frame: 1 year ]
    Number of participants with vital signs data meeting the following criteria is presented: (1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); (2) standing SBP <90 mmHg; (3) supine diastolic blood pressure (DBP) <50 mmHg; (4) standing DBP <50 mmHg; (5) supine pulse rate <40 beats per minute (bpm); (6) supine pulse rate >120 bpm; (7) standing pulse rate <40 bpm; (8) standing pulse rate >140 bpm; (9) maximum increase from baseline in supine SBP >= 30 mmHg; (10) maximum increase from baseline in standing SBP >= 30 mmHg; (11) maximum increase from baseline in supine DBP >= 20 mmHg; (12) maximum increase from baseline in standing DBP >= 20 mmHg; (13) maximum decrease from baseline in supine SBP >=30 mmHg; (14) maximum decrease from baseline in standing SBP >=30 mmHg; (15) maximum decrease from baseline in supine DBP >=20 mmHg; (16) maximum decrease from baseline in standing DBP >=20 mmHg.
  • Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria [ Time Frame: 1 year ]
    Maximum absolute values and increases from baseline were summarized for PR interval (interval between the start of the ECG 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), QRS complex (time from Q wave to the end of the S wave corresponding to ventricular depolarization), and QTcF interval (time from ECG Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula). Number of participants with ECG data meeting the following criteria is presented: (1) PR interval >=300 msec; (2) QRS complex >=140 msec; (3) QTcF interval: 450 to <480 msec; (4) QTcF interval: 480 to <500 msec; (5) QTcF interval >=500 msec; (6) PR interval increase from baseline >=25/50 percent; (7) QRS complex increase from baseline >=50 percent; (8) QTcF interval increase from baseline: 30 to <60 msec; (9) QTcF interval increase from baseline >=60 msec.
  • Number of Participants With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality) [ Time Frame: 1 year ]
    Number of participants with white blood cell (WBC) count and absolute neutrophil count (ANC) meeting the following criteria is presented: (1) WBC count <0.6 *the lower limit of normal (LLN); (2) WBC count >1.5 times the upper limit of normal (ULN); (3) ANC <0.8*LLN; and (4) ANC >1.2*ULN.
  • Number of Participants With Laboratory Test Abnormalities (Normal Baseline) [ Time Frame: 1 year ]
    The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, eosinophils, monocytes, basophils, and lymphocytes), chemistry (blood urea nitrogen/urea, creatinine, glucose, glycosylated hemoglobin [diabetics only], calcium, phosphorus, magnesium, creatine kinase, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (color, appearance, specific gravity, pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, and microscopy), and other tests (follicle stimulating hormone, urine drug screen, urine pregnancy [human chorionic gonadotropin, hCG], serum beta hCG). Abnormality was determined by the investigator.
  • Number of Participants With Adverse Events Related to Extrapyramidal Symptoms by Severity [ Time Frame: 1 year ]
    Adverse events related to extrapyramidal symptoms included dystonia, akathisia, tardive dyskinesia). Severity was assessed by the investigator. Mild means the AE didn't interfere with the participant's usual function. Moderate means the AE interfered to some extent the participant's usual function. Severe means the AE interfered significantly with the participant's usual function.
  • Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category [ Time Frame: Baseline (Day 1), Weeks 2 and 4, Months 3, 6, 9 and 12, follow-up visit (7-14 days after the last dose of Month 12) ]
    Columbia Suicide Severity Rating Scale (C-SSRS) was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior, and was used in this study. C-SSRS responses were mapped onto the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Number of participants with any of the following behaviors occurring since last visit was summarized: completed suicide; suicide attempt; preparatory acts towards suicide; suicidal ideation; self-injurious behavior (no suicidal intent).
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
  • White blood count and absolute neutrophil count [ Time Frame: Baseline to Follow-up visit (Day 365) ]
    Monitoring of ANC and WBC
  • Extrapyramidal symptoms [ Time Frame: Baseline to Follow-up visit (Day 365) ]
    Occurence of dystonia or akathisia
  • Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline to Follow-up Visit (Day 365) ]
    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").
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2018)
  • Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score [ Time Frame: Baseline (Day 1), Month 6, and Month 12 ]
    The UHDRS is a clinical rating scale developed to provide a uniform assessment of the clinical features and course of Huntington's disease (HD). The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. Total Motor Score (TMS) assesses motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural ability. The total motor impairment scores was the sum of all the individual 31 motor sub-items (each rated from 0 to 4), with higher scores indicating more severe motor impairment than lower scores. The range of TMS is 0-124.
  • Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score [ Time Frame: Baseline (Day 1), Month 6, and Month 12 ]
    The UHDRS is a clinical rating scale developed to provide a uniform assessment of the clinical features and course of Huntington's disease (HD). The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. Total Maximum Chorea (TMC) is a subset of the TMS assessment, and composed of the scoring of 7 chorea assessments (face, orobuccolingual, trunk, right and left upper extremities, right and left lower extremities). Each assessment is rated from 0 to 4 (absent to prolonged). TMC is obtained by adding up each of the separate scores, leading to max score of 28. The minimum score is 0. The higher the score, the worse the symptoms.
  • Absolute Value in Clinical Global Impression of Improvement (CGI-I) Score [ Time Frame: Month 6 and Month 12 ]
    The Clinical Global Impression of Improvement (CGI-I) is a global measure of improvement or change based on the clinician's assessment of all available clinical data obtained from interviewing the participant. The CGI-I consists of a single 7-point rating of total improvement or change from baseline severity, regardless of whether or not the change is due entirely to drug treatment. Raters select 1 response based on the following question, "Compared to your participant's condition at the beginning of treatment, how much has he/she changed?" Scores are: 1: Very much improved; 2: Much improved; 3: Minimally improved; 4: No change; 5: Minimally worse; 6: Much worse; or 7: Very much worse.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
  • Change from baseline in UHDRS Total Motor Score (TMS) after 6 and 12 months of treatment [ Time Frame: Baseline, 6 months and 12 months of treatment in the Open label ]
  • Change from baseline in UHDRS Total Maximum Chorea (TMC) after 6 and 12 months of treatment [ Time Frame: Baseline, 6 months and 12 months of treatment in the Open label ]
  • Change from baseline in • Clinical Global Impression-Improvement score after 6 and 12 months of treatment [ Time Frame: Baseline, 6 months and 12 months of treatment in the Open label ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open Label Extension Study To Investigate Long Term Safety, Tolerability And Efficacy Of Pf-02545920 In Subjects With Huntington's Disease Who Completed Study A8241021
Official Title  ICMJE An Open Label Extension Study To Investigate The Long Term Safety, Tolerability And Efficacy Of Pf-02545920 In Subjects With Huntington's Disease Who Previously Completed Study A8241021
Brief Summary This study is a 12 month open label extension study of PF-02545920 20 mg dosed BID following study A8241021 in subjects with HD. Primary endpoints will be to assess long-term safety and tolerability of 20 mg BID of PF-02545920. Secondary endpoints will be the change from baseline in the Total Motor Score (TMS)assessment, and/ior the Total maximum Chorea (TMC) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 6 and 12 months of treatment, and Clinical Global Impression-Improvement score after 6 and 12 months of treatment. Subjects, who were assigned to the 20 mg PF-02545920 dose group in the preceding A8241021 study, will receive 20 mg PF-02545920 without any titration. All other subjects will be titrated to the 20 mg BID dose as follows: 5 mg BID for 7 days, 10 mg BID for 7 days, 15 mg BID for 7 days, then 20 mg BID for the remainder of the treatment phase. Up to 260 subjects may take part in this open label extension
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Huntington's Disease
Intervention  ICMJE Drug: 20 mg BID of PF-02545920
All subject who completed A8241021 will receive 20 mg BID (with or without titration)
Study Arms  ICMJE
  • Experimental: 20 mg BID PF-02545920 non-titrated
    Subjects who received 20 mg BID in completed study A8241021 will continue to receive 20 mg BID PF-02545920
    Intervention: Drug: 20 mg BID of PF-02545920
  • Experimental: 20mg BID PF-02545920 titrated
    Subjects who received either Placebo or 5mg BID of PF-02545920 in completed study A8241021 will be titrated up to 20 mg with 5mg increment per week, over 4 weeks (5mg increment/wk)
    Intervention: Drug: 20 mg BID of PF-02545920
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: March 9, 2017)
188
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2015)
260
Actual Study Completion Date  ICMJE February 6, 2017
Actual Primary Completion Date February 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must have completed study A8241021
  • Diagnosis of HD, including ≥36 CAG repeats.

Exclusion Criteria:

  • Significant neurological disorder other than Huntington's disease.
  • WBC ≤ 3500/mm3 AND/OR ANC ≤ 2000/mm3 and history of neutropenia or myeolo-proliferative disorders.
  • Any drug related SAE experienced during study A8241021 which were not approved as acceptable for enrollment in A8241022.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 66 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,   Germany,   Poland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02342548
Other Study ID Numbers  ICMJE A8241022
2014-004900-31 ( EudraCT Number )
OPEN LABEL TO A8241021 ( Other Identifier: Alias Study 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 March 2018

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