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
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT02342548
Collaborator
(none)
188
50
2
23.4
3.8
0.2
Study Details
Study Description
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 |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
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
:
Feb 25, 2015
Actual Primary Completion Date
:
Feb 6, 2017
Actual Study Completion Date
:
Feb 6, 2017
Arms and Interventions
| 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)
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events [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) [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 [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 [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) [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) [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 [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 [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
- Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score [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 [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 [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
30 Years
to 66 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Kirkland Clinic of UAB Hospital | Birmingham | Alabama | United States | 35233 |
| 2 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
| 3 | Mayo Clinic Arizona | Scottsdale | Arizona | United States | 85259 |
| 4 | University of California, Irvine | Irvine | California | United States | 92697 |
| 5 | Ronald Reagan UCLA Medical Center Drug Information Center | Los Angeles | California | United States | 90095 |
| 6 | UCLA Neurology Clinic | Los Angeles | California | United States | 90095 |
| 7 | UCLA Radiology | Los Angeles | California | United States | 90095 |
| 8 | Rocky Mountain Movement Disorders Center | Englewood | Colorado | United States | 80113 |
| 9 | University of Florida Center for Movement Disorders & Neurorestoration | Gainesville | Florida | United States | 32607 |
| 10 | Indiana University Health Neuroscience Center | Indianapolis | Indiana | United States | 46202 |
| 11 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 12 | Albany Medical College | Albany | New York | United States | 12208 |
| 13 | Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | United States | 27157 |
| 14 | The Ohio State University | Columbus | Ohio | United States | 43221 |
| 15 | The Wexner Medical Center at the Ohio State University | Columbus | Ohio | United States | 43221 |
| 16 | The Wright Center of Innovation- The Ohio State University | Columbus | Ohio | United States | 43221 |
| 17 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 18 | The Centre For Huntington Disease, The University of British Columbia | Vancouver | British Columbia | Canada | V6T 2B5 |
| 19 | Center For Movement Disorders | Toronto | Ontario | Canada | M3B 2S7 |
| 20 | CHUM-Notre-Dame Hospital | Montreal | Quebec | Canada | H2L 4M1 |
| 21 | CHUM-Notre-Dame, Pharmacie | Montreal | Quebec | Canada | H4L 4M1 |
| 22 | Uniklinik RWTH Aachen | Aachen | Germany | 52074 | |
| 23 | Charité - Universitätsmedizin Berlin | Berlin | Germany | 10117 | |
| 24 | St. Josef Hospital | Bochum | Germany | 44791 | |
| 25 | Friedrich-Alexander-Universität | Erlangen | Germany | 91054 | |
| 26 | Universität zu Lübeck | Lübeck | Germany | 23562 | |
| 27 | Philipps Universitat Marburg | Marburg | Germany | 35043 | |
| 28 | Technische Universität München | Munchen | Germany | 81675 | |
| 29 | George-Huntington-Institut | Münster | Germany | 48149 | |
| 30 | Kbo-Isar-Amper-Klinikum gGmbH | Taufkirchen | Germany | 84416 | |
| 31 | Universitätsklinikum Ulm | Ulm | Germany | 89081 | |
| 32 | Universitaetsklinikum Wuerzburg | Wuerzburg | Germany | 97080 | |
| 33 | Copernicus Podmiot Leczniczy sp.zo.o | Gdansk | Poland | 80462 | |
| 34 | Krakowska Akademia Neurologii Sp. zo.o | Krakow | Poland | 31505 | |
| 35 | Solumed Centrum Medyczne | Poznan | Poland | 60-529 | |
| 36 | Instytut Psychiatrii i Neurologii, I Klinika Neurologiczna | Warszawa | Poland | 02957 | |
| 37 | Central Manchester University Hospitals NHS Foundation Trust | Oxford Road | Manchester | United Kingdom | M13 9WL |
| 38 | St Nicholas Hospital | Gosforth | Newcastle UPON TYNE | United Kingdom | NE3 3XT |
| 39 | Bimingham & Solihull Mental Health NHS Foundation Trust Department of Neuropsychiatry | Birmingham | WEST Midlands | United Kingdom | B15 2FG |
| 40 | NHS Grampian, Aberdeen Royal Infirmary, Clinical Genetics Centre | Aberdeen | United Kingdom | AB25 2ZA | |
| 41 | Institute of Psychological Medicine and Clinical Neurosciences | Cardiff | United Kingdom | CF14 4XW | |
| 42 | NHS Greater Glasgow and Clyde | Glasgow | United Kingdom | G51 4TF | |
| 43 | Guy's and St. Thomas' NHS Foundation Trust | London | United Kingdom | SE19RT | |
| 44 | University College London Hospitals Huntington's Diesease | London | United Kingdom | wc1b 5eh | |
| 45 | University College London Hospitals NHS Foundation Trust | London | United Kingdom | WC1N 3BG | |
| 46 | The National Institute for Health Research / Wellcome Trust Clinical Research Facility | Manchester | United Kingdom | M13 9WL | |
| 47 | Newcastle Magnetic Resonance Centre | Newcastle upon Tyne | United Kingdom | NE4 5PL | |
| 48 | Oxford University Hospitals NHS Trust | Oxford | United Kingdom | OX3 9DU | |
| 49 | Sheffield Teaching Hospital NHS Foundation Trust | Sheffield | United Kingdom | S10 2JF | |
| 50 | 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)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02342548
Other Study ID Numbers:
- A8241022
- 2014-004900-31
- OPEN LABEL TO A8241021
First Posted:
Jan 21, 2015
Last Update Posted:
Apr 23, 2018
Last Verified:
Mar 1, 2018
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | This was an open-label extension study conducted in participants who had completed study A8241021 (NCT02197130). Treatment assignment was double-blinded from Day 1 to Day 21, and became open-label from Day 22, since all participants began receiving the same dose level from Day 22. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Period Title: Overall Study | |||
| STARTED | 51 | 71 | 66 |
| COMPLETED | 17 | 9 | 23 |
| NOT COMPLETED | 34 | 62 | 43 |
Baseline Characteristics
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Total of all reporting groups |
| Overall Participants | 51 | 71 | 66 | 188 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
50.2
(9.4)
|
48.4
(8.6)
|
51.3
(9.4)
|
49.9
(9.1)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
25
49%
|
33
46.5%
|
43
65.2%
|
101
53.7%
|
| Male |
26
51%
|
38
53.5%
|
23
34.8%
|
87
46.3%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| White |
50
98%
|
68
95.8%
|
66
100%
|
184
97.9%
|
| Other |
1
2%
|
3
4.2%
|
0
0%
|
4
2.1%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events |
|---|---|
| Description | 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. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all participants who entered the extension study with at least 1 dose of study medication. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 66 |
| AEs |
39
76.5%
|
63
88.7%
|
62
93.9%
|
| SAEs |
7
13.7%
|
9
12.7%
|
5
7.6%
|
| Title | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) |
|---|---|
| Description | 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. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all participants who entered the extension study with at least 1 dose of study medication. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 66 |
| Count of Participants [Participants] |
19
37.3%
|
27
38%
|
28
42.4%
|
| Title | Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria |
|---|---|
| Description | 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. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who entered the extension study with at least 1 dose of study medication, and with available data for at least 1 category. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 66 |
| Supine SBP <90 mmHg |
0
0%
|
0
0%
|
0
0%
|
| Standing SBP <90 mmHg |
0
0%
|
1
1.4%
|
0
0%
|
| Supine DBP <50 mmHg |
0
0%
|
1
1.4%
|
0
0%
|
| Standing DBP <50 mmHg |
0
0%
|
1
1.4%
|
0
0%
|
| Supine pulse rate <40 bpm |
0
0%
|
0
0%
|
0
0%
|
| Supine pulse rate >120 bpm |
0
0%
|
0
0%
|
0
0%
|
| Standing pulse rate <40 bpm |
0
0%
|
0
0%
|
0
0%
|
| Standing pulse rate >140 bpm |
0
0%
|
0
0%
|
0
0%
|
| Supine SBP increase from baseline >=30 mmHg |
3
5.9%
|
1
1.4%
|
6
9.1%
|
| Standing SBP increase from baseline >=30 mmHg |
1
2%
|
6
8.5%
|
4
6.1%
|
| Supine DBP increase from baseline >=20 mmHg |
4
7.8%
|
2
2.8%
|
6
9.1%
|
| Standing DBP increase from baseline >=20 mmHg |
3
5.9%
|
8
11.3%
|
2
3%
|
| Supine SBP decrease from baseline >=30 mmHg |
2
3.9%
|
1
1.4%
|
4
6.1%
|
| Standing SBP decrease from baseline >=30 mmHg |
0
0%
|
1
1.4%
|
2
3%
|
| Supine DBP decrease from baseline >=20 mmHg |
0
0%
|
2
2.8%
|
7
10.6%
|
| Standing DBP decrease from baseline >=20 mmHg |
1
2%
|
4
5.6%
|
6
9.1%
|
| Title | Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria |
|---|---|
| Description | 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. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who entered the extension study with at least 1 dose of study medication, and with available data for at least 1 category. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 66 |
| PR interval >=300 msec |
0
0%
|
0
0%
|
0
0%
|
| QRS complex >=140 msec |
0
0%
|
0
0%
|
0
0%
|
| QTcF interval: 450 to <480 msec |
2
3.9%
|
2
2.8%
|
2
3%
|
| QTcF interval: 480 to <500 msec |
0
0%
|
0
0%
|
1
1.5%
|
| QTcF interval >=500 msec |
0
0%
|
0
0%
|
0
0%
|
| PR interval increase from baseline >=25/50 percent |
0
0%
|
0
0%
|
0
0%
|
| QRS complex increase from baseline >=50 percent |
0
0%
|
0
0%
|
0
0%
|
| QTcF increase from baseline: 30 to <60 msec |
3
5.9%
|
5
7%
|
4
6.1%
|
| QTcF increase from baseline >=60 msec |
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality) |
|---|---|
| Description | 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. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who entered the extension study with at least 1 dose of study medication, and with available data for at least 1 category. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 65 |
| WBC < 0.6*LLN |
0
0%
|
0
0%
|
0
0%
|
| WBC > 1.5*ULN |
1
2%
|
0
0%
|
1
1.5%
|
| ANC < 0.8*LLN |
1
2%
|
0
0%
|
0
0%
|
| ANC > 1.2*ULN |
3
5.9%
|
4
5.6%
|
7
10.6%
|
| Title | Number of Participants With Laboratory Test Abnormalities (Normal Baseline) |
|---|---|
| Description | 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. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all participants who entered the extension study with at least 1 dose of study medication. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 66 |
| Count of Participants [Participants] |
13
25.5%
|
22
31%
|
23
34.8%
|
| Title | Number of Participants With Adverse Events Related to Extrapyramidal Symptoms by Severity |
|---|---|
| Description | 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. |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all participants who entered the extension study with at least 1 dose of study medication. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 66 |
| Mild dystonia |
0
0%
|
1
1.4%
|
0
0%
|
| Moderate dystonia |
0
0%
|
1
1.4%
|
1
1.5%
|
| Severe dystonia |
0
0%
|
0
0%
|
0
0%
|
| Mild akathisia |
1
2%
|
1
1.4%
|
0
0%
|
| Moderate akathisia |
0
0%
|
1
1.4%
|
3
4.5%
|
| Severe akathisia |
0
0%
|
0
0%
|
1
1.5%
|
| Mild dyskinesia |
0
0%
|
2
2.8%
|
4
6.1%
|
| Moderate dyskinesia |
1
2%
|
1
1.4%
|
2
3%
|
| Severe dyskinesia |
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category |
|---|---|
| Description | 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). |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who entered the extension study with at least 1 dose of study medication, and with available data for at least 1 time point. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 51 | 71 | 66 |
| Day 1: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Day 1: suicide attempt |
0
0%
|
0
0%
|
0
0%
|
| Day 1: preparatory acts towards suicide |
0
0%
|
0
0%
|
0
0%
|
| Day 1: suicidal ideation |
0
0%
|
1
1.4%
|
1
1.5%
|
| Day 1: self-injurious behavior |
0
0%
|
0
0%
|
0
0%
|
| Week 2: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Week 2: suicide attempt |
0
0%
|
0
0%
|
0
0%
|
| Week 2: preparatory acts towards suicide |
0
0%
|
0
0%
|
0
0%
|
| Week 2: suicidal ideation |
0
0%
|
0
0%
|
1
1.5%
|
| Week 2: self-injurious behavior |
0
0%
|
0
0%
|
0
0%
|
| Week 4: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Week 4: suicide attempt |
0
0%
|
0
0%
|
0
0%
|
| Week 4: preparatory acts towards suicide |
0
0%
|
0
0%
|
0
0%
|
| Week 4: suicidal ideation |
0
0%
|
1
1.4%
|
1
1.5%
|
| Week 4: self-injurious behavior |
0
0%
|
0
0%
|
0
0%
|
| Month 3: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Month 3: suicide attempt |
0
0%
|
0
0%
|
0
0%
|
| Month 3: preparatory acts towards suicide |
0
0%
|
0
0%
|
0
0%
|
| Month 3: suicidal ideation |
1
2%
|
0
0%
|
1
1.5%
|
| Month 3: self-injurious behavior |
0
0%
|
0
0%
|
0
0%
|
| Month 6: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Month 6: suicide attempt |
0
0%
|
0
0%
|
0
0%
|
| Month 6: preparatory acts towards suicide |
0
0%
|
0
0%
|
0
0%
|
| Month 6: suicidal ideation |
1
2%
|
0
0%
|
1
1.5%
|
| Month 6: self-injurious behavior |
0
0%
|
0
0%
|
0
0%
|
| Month 9: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Month 9: suicide attempt |
0
0%
|
0
0%
|
0
0%
|
| Month 9: preparatory acts towards suicide |
0
0%
|
0
0%
|
0
0%
|
| Month 9: suicidal ideation |
0
0%
|
1
1.4%
|
0
0%
|
| Month 9: self-injurious behavior |
0
0%
|
0
0%
|
0
0%
|
| Month 12: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Month 12: suicide attempt |
1
2%
|
0
0%
|
0
0%
|
| Month 12: preparatory acts towards suicide |
1
2%
|
0
0%
|
0
0%
|
| Month 12: suicidal ideation |
3
5.9%
|
0
0%
|
3
4.5%
|
| Month 12: self-injurious behavior |
1
2%
|
0
0%
|
0
0%
|
| Follow up: completed suicide |
0
0%
|
0
0%
|
0
0%
|
| Follow up: suicide attempt |
0
0%
|
0
0%
|
0
0%
|
| Follow up: preparatory acts towards suicide |
0
0%
|
0
0%
|
0
0%
|
| Follow up: suicidal ideation |
1
2%
|
0
0%
|
0
0%
|
| Follow up: self-injurious behavior |
0
0%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 1), Month 6, and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all participants who had an open-label extension study baseline efficacy evaluation and completed at least Week 2 visit with a valid UHDRS TMS score, and took >=1 dose of open-label study medication. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 50 | 70 | 62 |
| Month 6 |
2.4
(7.21)
|
3.5
(7.61)
|
0.7
(7.43)
|
| Month 12 |
4.9
(10.17)
|
3.3
(6.71)
|
0.6
(8.24)
|
| Title | Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Day 1), Month 6, and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all participants who had an open-label extension study baseline efficacy evaluation and completed at least Week 2 visit with a valid UHDRS TMS score, and took >=1 dose of open-label study medication. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 50 | 70 | 62 |
| Month 6 |
0.1
(3.12)
|
1.3
(3.97)
|
1.4
(4.14)
|
| Month 12 |
0.1
(4.92)
|
0.8
(1.64)
|
0.7
(3.51)
|
| Title | Absolute Value in Clinical Global Impression of Improvement (CGI-I) Score |
|---|---|
| Description | 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. |
| Time Frame | Month 6 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all participants who had an open-label extension study baseline efficacy evaluation and completed at least Week 2 visit with a valid UHDRS TMS score, and took >=1 dose of open-label study medication. |
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 |
|---|---|---|---|
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). |
| Measure Participants | 50 | 70 | 62 |
| Month 6 |
3.9
(1.04)
|
4.2
(1.03)
|
3.7
(1.19)
|
| Month 12 |
3.5
(1.30)
|
4.6
(1.13)
|
4.0
(1.21)
|
Adverse Events
| Time Frame | 1 year | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 | |||
| Arm/Group Description | Participants who received PF-02545920 20 mg twice daily (BID) in Study A8241021 continued to receive PF-02545920 20 mg BID for 12 months in this study. Four 5-mg tablets were administered orally each time. | Participants who received PF-02545920 5 mg twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | Participants who received placebo twice daily (BID) in Study A8241021 were administered PF-02545920 orally according to a double-blind titration schedule in this study: 5 mg BID for 7 days (one 5-mg tablet and 3 placebo tablets); 10 mg BID for 7 days (two 5-mg tablets and 2 placebo tablets); 15 mg BID for 7 days (three 5-mg tablets and 1 placebo tablet); 20 mg BID to Month 12 (four 5-mg tablets). | |||
All Cause Mortality |
||||||
| 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/51 (0%) | 0/71 (0%) | 0/66 (0%) | |||
Serious Adverse Events |
||||||
| 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/51 (13.7%) | 9/71 (12.7%) | 5/66 (7.6%) | |||
| Congenital, familial and genetic disorders | ||||||
| Huntington's disease | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Gastrointestinal disorders | ||||||
| Dysphagia | 0/51 (0%) | 0/71 (0%) | 1/66 (1.5%) | |||
| Pancreatitis | 0/51 (0%) | 0/71 (0%) | 1/66 (1.5%) | |||
| General disorders | ||||||
| Complication associated with device | 1/51 (2%) | 0/71 (0%) | 0/66 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 0/51 (0%) | 0/71 (0%) | 1/66 (1.5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Cervical vertebral fracture | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Fall | 0/51 (0%) | 1/71 (1.4%) | 1/66 (1.5%) | |||
| Investigations | ||||||
| Blood creatine phosphokinase increased | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Weight decreased | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 1/51 (2%) | 0/71 (0%) | 0/66 (0%) | |||
| Intervertebral disc protrusion | 1/51 (2%) | 0/71 (0%) | 0/66 (0%) | |||
| Osteoarthritis | 1/51 (2%) | 0/71 (0%) | 0/66 (0%) | |||
| Nervous system disorders | ||||||
| Chorea | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Hyperkinesia | 2/51 (3.9%) | 0/71 (0%) | 0/66 (0%) | |||
| Syncope | 0/51 (0%) | 1/71 (1.4%) | 1/66 (1.5%) | |||
| Transient ischaemic attack | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Psychiatric disorders | ||||||
| Agitation | 0/51 (0%) | 0/71 (0%) | 1/66 (1.5%) | |||
| Depression | 1/51 (2%) | 0/71 (0%) | 0/66 (0%) | |||
| Panic attack | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Suicide attempt | 1/51 (2%) | 0/71 (0%) | 0/66 (0%) | |||
| Renal and urinary disorders | ||||||
| Urinary tract disorder | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Prostatomegaly | 1/51 (2%) | 0/71 (0%) | 0/66 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/51 (0%) | 1/71 (1.4%) | 0/66 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| 20 mg PF-02545920 | 5 mg PF-02545920 Titration up to 20 mg | Placebo and Titration up to 20 mg PF-02545920 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 32/51 (62.7%) | 53/71 (74.6%) | 54/66 (81.8%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 2/51 (3.9%) | 6/71 (8.5%) | 4/66 (6.1%) | |||
| Dysphagia | 2/51 (3.9%) | 3/71 (4.2%) | 4/66 (6.1%) | |||
| Nausea | 2/51 (3.9%) | 9/71 (12.7%) | 8/66 (12.1%) | |||
| Vomiting | 1/51 (2%) | 5/71 (7%) | 3/66 (4.5%) | |||
| General disorders | ||||||
| Fatigue | 2/51 (3.9%) | 9/71 (12.7%) | 9/66 (13.6%) | |||
| Infections and infestations | ||||||
| Viral upper respiratory tract infection | 4/51 (7.8%) | 3/71 (4.2%) | 7/66 (10.6%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 6/51 (11.8%) | 15/71 (21.1%) | 8/66 (12.1%) | |||
| Investigations | ||||||
| Weight decreased | 3/51 (5.9%) | 7/71 (9.9%) | 11/66 (16.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 3/51 (5.9%) | 6/71 (8.5%) | 4/66 (6.1%) | |||
| Muscle spasms | 3/51 (5.9%) | 0/71 (0%) | 0/66 (0%) | |||
| Nervous system disorders | ||||||
| Akathisia | 1/51 (2%) | 2/71 (2.8%) | 4/66 (6.1%) | |||
| Chorea | 11/51 (21.6%) | 11/71 (15.5%) | 14/66 (21.2%) | |||
| Dizziness | 0/51 (0%) | 9/71 (12.7%) | 5/66 (7.6%) | |||
| Dyskinesia | 1/51 (2%) | 3/71 (4.2%) | 6/66 (9.1%) | |||
| Headache | 1/51 (2%) | 5/71 (7%) | 3/66 (4.5%) | |||
| Hyperkinesia | 7/51 (13.7%) | 0/71 (0%) | 2/66 (3%) | |||
| Sedation | 1/51 (2%) | 2/71 (2.8%) | 5/66 (7.6%) | |||
| Somnolence | 1/51 (2%) | 4/71 (5.6%) | 9/66 (13.6%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 2/51 (3.9%) | 5/71 (7%) | 7/66 (10.6%) | |||
| Depression | 3/51 (5.9%) | 3/71 (4.2%) | 5/66 (7.6%) | |||
| Insomnia | 2/51 (3.9%) | 4/71 (5.6%) | 9/66 (13.6%) | |||
| Restlessness | 1/51 (2%) | 2/71 (2.8%) | 5/66 (7.6%) | |||
| Sleep disorder | 3/51 (5.9%) | 3/71 (4.2%) | 2/66 (3%) | |||
Limitations/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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02342548
Other Study ID Numbers:
- A8241022
- 2014-004900-31
- OPEN LABEL TO A8241021
First Posted:
Jan 21, 2015
Last Update Posted:
Apr 23, 2018
Last Verified:
Mar 1, 2018