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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

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

Condition or disease Intervention/treatment Phase
Huntington's Disease Drug: 20 mg BID of PF-02545920 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 25, 2015
Actual Primary Completion Date : February 6, 2017
Actual Study Completion Date : February 6, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: 20 mg BID of PF-02545920
All subject who completed A8241021 will receive 20 mg BID (with or without titration)

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)
Drug: 20 mg BID of PF-02545920
All subject who completed A8241021 will receive 20 mg BID (with or without titration)




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 66 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT02342548


  Hide Study Locations
Locations
United States, Alabama
The Kirkland Clinic of UAB Hospital
Birmingham, Alabama, United States, 35233
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
University of California, Irvine
Irvine, California, United States, 92697
Ronald Reagan UCLA Medical Center Drug Information Center
Los Angeles, California, United States, 90095
UCLA Neurology Clinic
Los Angeles, California, United States, 90095
UCLA Radiology
Los Angeles, California, United States, 90095
United States, Colorado
Rocky Mountain Movement Disorders Center
Englewood, Colorado, United States, 80113
United States, Florida
University of Florida Center for Movement Disorders & Neurorestoration
Gainesville, Florida, United States, 32607
United States, Indiana
Indiana University Health Neuroscience Center
Indianapolis, Indiana, United States, 46202
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Albany Medical College
Albany, New York, United States, 12208
United States, North Carolina
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43221
The Wexner Medical Center at the Ohio State University
Columbus, Ohio, United States, 43221
The Wright Center of Innovation- The Ohio State University
Columbus, Ohio, United States, 43221
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Canada, British Columbia
The Centre For Huntington Disease, The University of British Columbia
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Ontario
Center For Movement Disorders
Toronto, Ontario, Canada, M3B 2S7
Canada, Quebec
CHUM-Notre-Dame Hospital
Montreal, Quebec, Canada, H2L 4M1
CHUM-Notre-Dame, Pharmacie
Montreal, Quebec, Canada, H4L 4M1
Germany
Uniklinik RWTH Aachen
Aachen, Germany, 52074
Charité - Universitätsmedizin Berlin
Berlin, Germany, 10117
St. Josef Hospital
Bochum, Germany, 44791
Friedrich-Alexander-Universität
Erlangen, Germany, 91054
Universität zu Lübeck
Lübeck, Germany, 23562
Philipps Universitat Marburg
Marburg, Germany, 35043
Technische Universität München
Munchen, Germany, 81675
George-Huntington-Institut
Münster, Germany, 48149
Kbo-Isar-Amper-Klinikum gGmbH
Taufkirchen, Germany, 84416
Universitätsklinikum Ulm
Ulm, Germany, 89081
Universitaetsklinikum Wuerzburg
Wuerzburg, Germany, 97080
Poland
Copernicus Podmiot Leczniczy sp.zo.o
Gdansk, Poland, 80462
Krakowska Akademia Neurologii Sp. zo.o
Krakow, Poland, 31505
Solumed Centrum Medyczne
Poznan, Poland, 60-529
Instytut Psychiatrii i Neurologii, I Klinika Neurologiczna
Warszawa, Poland, 02957
United Kingdom
Central Manchester University Hospitals NHS Foundation Trust
Oxford Road, Manchester, United Kingdom, M13 9WL
St Nicholas Hospital
Gosforth, Newcastle UPON TYNE, United Kingdom, NE3 3XT
Bimingham & Solihull Mental Health NHS Foundation Trust Department of Neuropsychiatry
Birmingham, WEST Midlands, United Kingdom, B15 2FG
NHS Grampian, Aberdeen Royal Infirmary, Clinical Genetics Centre
Aberdeen, United Kingdom, AB25 2ZA
Institute of Psychological Medicine and Clinical Neurosciences
Cardiff, United Kingdom, CF14 4XW
NHS Greater Glasgow and Clyde
Glasgow, United Kingdom, G51 4TF
Guy's and St. Thomas' NHS Foundation Trust
London, United Kingdom, SE19RT
University College London Hospitals Huntington's Diesease
London, United Kingdom, wc1b 5eh
University College London Hospitals NHS Foundation Trust
London, United Kingdom, WC1N 3BG
The National Institute for Health Research / Wellcome Trust Clinical Research Facility
Manchester, United Kingdom, M13 9WL
Newcastle Magnetic Resonance Centre
Newcastle upon Tyne, United Kingdom, NE4 5PL
Oxford University Hospitals NHS Trust
Oxford, United Kingdom, OX3 9DU
Sheffield Teaching Hospital NHS Foundation Trust
Sheffield, United Kingdom, S10 2JF
University Hospital Southampton NHS Foundation Trust, Wessex Neurological Centre
Southampton, United Kingdom, SO16 6YD
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] March 29, 2017
Study Protocol  [PDF] October 23, 2014


Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02342548     History of Changes
Other Study ID Numbers: A8241022
2014-004900-31 ( EudraCT Number )
OPEN LABEL TO A8241021 ( Other Identifier: Alias Study Number )
First Posted: January 21, 2015    Key Record Dates
Results First Posted: April 23, 2018
Last Update Posted: April 23, 2018
Last Verified: March 2018

Keywords provided by Pfizer:
Huntington; chorea; total motor score; CAG repeat: total functional capacity; motor cognitive and behavioral symptoms

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders