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

Huntington's Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02342548
• Other study ID #: A8241022
• Secondary ID: 2014-004900-31OP
• Status: Terminated
• Phase: Phase 2
• First received: January 15, 2015
• Last updated: March 23, 2018
• Start date: February 25, 2015
• Est. completion date: February 6, 2017

Study information

• Verified date: March 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 188
• Est. completion date: February 6, 2017
• Est. primary completion date: February 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 66 Years

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

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

Locations

Country	Name	City	State
Canada	CHUM-Notre-Dame Hospital	Montreal	Quebec
Canada	CHUM-Notre-Dame, Pharmacie	Montreal	Quebec
Canada	Center For Movement Disorders	Toronto	Ontario
Canada	The Centre For Huntington Disease, The University of British Columbia	Vancouver	British Columbia
Germany	Uniklinik RWTH Aachen	Aachen
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	St. Josef Hospital	Bochum
Germany	Friedrich-Alexander-Universität	Erlangen
Germany	Universität zu Lübeck	Lübeck
Germany	Philipps Universitat Marburg	Marburg
Germany	Technische Universität München	Munchen
Germany	George-Huntington-Institut	Münster
Germany	Kbo-Isar-Amper-Klinikum gGmbH	Taufkirchen
Germany	Universitätsklinikum Ulm	Ulm
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg
Poland	Copernicus Podmiot Leczniczy sp.zo.o	Gdansk
Poland	Krakowska Akademia Neurologii Sp. zo.o	Krakow
Poland	Solumed Centrum Medyczne	Poznan
Poland	Instytut Psychiatrii i Neurologii, I Klinika Neurologiczna	Warszawa
United Kingdom	NHS Grampian, Aberdeen Royal Infirmary, Clinical Genetics Centre	Aberdeen
United Kingdom	Bimingham & Solihull Mental Health NHS Foundation Trust Department of Neuropsychiatry	Birmingham	WEST Midlands
United Kingdom	Institute of Psychological Medicine and Clinical Neurosciences	Cardiff
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	St Nicholas Hospital	Gosforth	Newcastle UPON TYNE
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust	London
United Kingdom	University College London Hospitals Huntington's Diesease	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United Kingdom	The National Institute for Health Research / Wellcome Trust Clinical Research Facility	Manchester
United Kingdom	Newcastle Magnetic Resonance Centre	Newcastle upon Tyne
United Kingdom	Oxford University Hospitals NHS Trust	Oxford
United Kingdom	Central Manchester University Hospitals NHS Foundation Trust	Oxford Road	Manchester
United Kingdom	Sheffield Teaching Hospital NHS Foundation Trust	Sheffield
United Kingdom	University Hospital Southampton NHS Foundation Trust, Wessex Neurological Centre	Southampton
United States	Albany Medical College	Albany	New York
United States	The Kirkland Clinic of UAB Hospital	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	The Ohio State University	Columbus	Ohio
United States	The Wexner Medical Center at the Ohio State University	Columbus	Ohio
United States	The Wright Center of Innovation- The Ohio State University	Columbus	Ohio
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	University of Florida Center for Movement Disorders & Neurorestoration	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Health Neuroscience Center	Indianapolis	Indiana
United States	University of California, Irvine	Irvine	California
United States	Ronald Reagan UCLA Medical Center Drug Information Center	Los Angeles	California
United States	UCLA Neurology Clinic	Los Angeles	California
United States	UCLA Radiology	Los Angeles	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score	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.	Baseline (Day 1), Month 6, and Month 12
Secondary	Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score	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.	Baseline (Day 1), Month 6, and Month 12
Secondary	Absolute Value in Clinical Global Impression of Improvement (CGI-I) Score	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.	Month 6 and Month 12

External Links

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