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

NCT02342548 | Terminated Phase 2 Results DMC

• 3 other identifiers: A82410222014-004900-31OPEN LABEL TO A8241021
• Study Type: interventional
• Target: 188
• Locations: 5 countries
• Sites: 50

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

Conditions

Huntington's Disease

Keywords

Huntington; chorea; total motor score; CAG repeat: total functional capacity; motor cognitive and behavioral symptoms

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events

  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.

  1 year

• Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

  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.

  1 year

• Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria

  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.

  1 year

• Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria

  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.

  1 year

• Number of Participants With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality)

  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.

  1 year

• Number of Participants With Laboratory Test Abnormalities (Normal Baseline)

  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.

  1 year

• Number of Participants With Adverse Events Related to Extrapyramidal Symptoms by Severity

  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.

  1 year

• Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category

  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).

  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)

Secondary Outcomes (3)

• Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score

  Baseline (Day 1), Month 6, and Month 12

• Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score

  Baseline (Day 1), Month 6, and Month 12

• Absolute Value in Clinical Global Impression of Improvement (CGI-I) Score

  Month 6 and Month 12

Study Arms (2)

20 mg BID PF-02545920 non-titrated

EXPERIMENTAL

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

20mg BID PF-02545920 titrated

EXPERIMENTAL

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

Interventions

20 mg BID of PF-02545920 DRUG

All subject who completed A8241021 will receive 20 mg BID (with or without titration)

20 mg BID PF-02545920 non-titrated; 20mg BID PF-02545920 titrated

Eligibility Criteria

• Age: 30 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (50)

The Kirkland Clinic of UAB Hospital

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

Ronald Reagan UCLA Medical Center Drug Information Center

Los Angeles, California, 90095, United States

Location

UCLA Neurology Clinic

Los Angeles, California, 90095, United States

Location

UCLA Radiology

Los Angeles, California, 90095, United States

Location

Rocky Mountain Movement Disorders Center

Englewood, Colorado, 80113, United States

Location

University of Florida Center for Movement Disorders & Neurorestoration

Gainesville, Florida, 32607, United States

Location

Indiana University Health Neuroscience Center

Indianapolis, Indiana, 46202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

The Wexner Medical Center at the Ohio State University

Columbus, Ohio, 43221, United States

Location

The Wright Center of Innovation- The Ohio State University

Columbus, Ohio, 43221, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

The Centre For Huntington Disease, The University of British Columbia

Vancouver, British Columbia, V6T 2B5, Canada

Location

Center For Movement Disorders

Toronto, Ontario, M3B 2S7, Canada

Location

CHUM-Notre-Dame Hospital

Montreal, Quebec, H2L 4M1, Canada

Location

CHUM-Notre-Dame, Pharmacie

Montreal, Quebec, H4L 4M1, Canada

Location

Uniklinik RWTH Aachen

Aachen, 52074, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

St. Josef Hospital

Bochum, 44791, Germany

Location

Friedrich-Alexander-Universität

Erlangen, 91054, Germany

Location

Universität zu Lübeck

Lübeck, 23562, Germany

Location

Philipps Universitat Marburg

Marburg, 35043, Germany

Location

Technische Universität München

München, 81675, Germany

Location

George-Huntington-Institut

Münster, 48149, Germany

Location

Kbo-Isar-Amper-Klinikum gGmbH

Taufkirchen, 84416, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Copernicus Podmiot Leczniczy sp.zo.o

Gdansk, 80462, Poland

Location

Krakowska Akademia Neurologii Sp. zo.o

Krakow, 31505, Poland

Location

Solumed Centrum Medyczne

Poznan, 60-529, Poland

Location

Instytut Psychiatrii i Neurologii, I Klinika Neurologiczna

Warsaw, 02957, Poland

Location

Central Manchester University Hospitals NHS Foundation Trust

Oxford Road, Manchester, M13 9WL, United Kingdom

Location

St Nicholas Hospital

Gosforth, Newcastle UPON TYNE, NE3 3XT, United Kingdom

Location

Bimingham & Solihull Mental Health NHS Foundation Trust Department of Neuropsychiatry

Birmingham, WEST Midlands, B15 2FG, United Kingdom

Location

NHS Grampian, Aberdeen Royal Infirmary, Clinical Genetics Centre

Aberdeen, AB25 2ZA, United Kingdom

Location

Institute of Psychological Medicine and Clinical Neurosciences

Cardiff, CF14 4XW, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, G51 4TF, United Kingdom

Location

Guy's and St. Thomas' NHS Foundation Trust

London, SE19RT, United Kingdom

Location

University College London Hospitals Huntington's Diesease

London, wc1b 5eh, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, WC1N 3BG, United Kingdom

Location

The National Institute for Health Research / Wellcome Trust Clinical Research Facility

Manchester, M13 9WL, United Kingdom

Location

Newcastle Magnetic Resonance Centre

Newcastle upon Tyne, NE4 5PL, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, OX3 9DU, United Kingdom

Location

Sheffield Teaching Hospital NHS Foundation Trust

Sheffield, S10 2JF, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust, Wessex Neurological Centre

Southampton, SO16 6YD, United Kingdom

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Huntington Disease; Chorea; Behavioral Symptoms

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Limitations and Caveats

This study was terminated on 15 December 2016 due to study A8241021 showing no significant difference on primary endpoint between PF-02545920 and placebo. No safety concerns were associated with this termination.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 21, 2015
• Study Start: February 25, 2015
• Primary Completion: February 6, 2017
• Study Completion: February 6, 2017
• Last Updated: April 23, 2018
• Results First Posted: April 23, 2018

Record last verified: 2018-03

Locations

PL (4); US (17); GB (14); DE (11); CA (4)