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Clinical Trial Results:
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

Summary
EudraCT number	2014-004900-31
Trial protocol	DE
Global end of trial date	06 Feb 2017

Results information
Results version number	v1(current)
This version publication date	10 Feb 2018
First version publication date	10 Feb 2018
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

A8241022

ISRCTN number

US NCT number

NCT02342548

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer, Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer Clinical Trials.gov Call Center Pfizer Clinical Trials.gov Call Center, Pfizer, Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

06 Feb 2017

Is this the analysis of the primary completion data?

Yes

Primary completion date

06 Feb 2017

Global end of trial reached?

Yes

Global end of trial date

06 Feb 2017

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective of this study was to assess long-term safety and tolerability of 20 mg twice daily (BID) of PF-02545920 in subjects with Huntington's Disease (HD).

Protection of trial subjects

This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Feb 2015

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

1 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 15

Country: Number of subjects enrolled

Germany: 65

Country: Number of subjects enrolled

Poland: 22

Country: Number of subjects enrolled

United Kingdom: 42

Country: Number of subjects enrolled

United States: 44

Worldwide total number of subjects

188

EEA total number of subjects

129

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

182

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This was an open-label extension study conducted in subjects 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 subjects began receiving the same dose level from Day 22.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

20 mg PF-02545920

Arm description

Subjects 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.

Arm type

Experimental

Investigational medicinal product name

PF-02545920

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received blinded PF-02545920 20 mg twice daily (BID) from Day 1 to Day 22. Starting from Day 22, the subjects received open-label PF-02545920 20 mg BID to Month 12. Four 5-mg tablets were administered orally each time.

5 mg PF-02545920 Titration up to 20 mg

Arm description

Subjects 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).

Arm type

Experimental

Investigational medicinal product name

PF-02545920

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received PF-02545920 orally according to a double-blind titration schedule: 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) from Day 1 to Day 21. Starting from Day 22, the subjects received open-label PF-02545920 20 mg BID to Month 12 (four 5-mg tablets).

Placebo and Titration up to 20 mg PF-02545920

Arm description

Subjects 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).

Arm type

Experimental

Investigational medicinal product name

PF-02545920

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Started	51	71	66
Completed	17	9	23
Not completed	34	62	43
Consent withdrawn by subject	1	3	4
Adverse event, non-fatal	12	17	13
Study terminated by sponsor	20	39	25
Unspecified	1	1	1
Lost to follow-up	-	1	-
Protocol deviation	-	1	-

Baseline characteristics

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Reporting group title

20 mg PF-02545920

Reporting group description

Reporting group title

5 mg PF-02545920 Titration up to 20 mg

Reporting group description

Reporting group title

Placebo and Titration up to 20 mg PF-02545920

Reporting group description

Reporting group values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920	Total
Number of subjects	51	71	66	188
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	48	69	65	182
From 65-84 years	3	2	1	6
85 years and over	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	50.2 ± 9.4	48.4 ± 8.6	51.3 ± 9.4	-
Sex: Female, Male
Units: Subjects
Female	25	33	43	101
Male	26	38	23	87

End points

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Reporting group title

20 mg PF-02545920

Reporting group description

Reporting group title

5 mg PF-02545920 Titration up to 20 mg

Reporting group description

Reporting group title

Placebo and Titration up to 20 mg PF-02545920

Reporting group description

Primary: Number of Subjects With Treatment-Emergent Adverse Events and Serious Adverse Events

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End point title

Number of Subjects With Treatment-Emergent Adverse Events and Serious Adverse Events ^[1]

End point description

An adverse event (AE) was any untoward medical occurrence in a clinical investigation subject 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. Safety analysis population was used for analysis, which included all subjects who entered the extension study with at least 1 dose of study medication.

End point type

Primary

End point timeframe

1 year

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	66
Units: subjects
AEs	39	63	62
SAEs	7	9	5

No statistical analyses for this end point

Primary: Number of Subjects With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

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End point title

Number of Subjects With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) ^[2]

End point description

Lab test included: hematology (hemoglobin, hematocrit, red blood cell, platelet and 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 and alanine aminotransferase, lactate dehydrogenase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (color, appearance, specific gravity, pH, qualitative glucose, protein and blood, ketones, nitrites, leukocyte esterase and microscopy), and other tests (follicle stimulating hormone, urine drug screen, urine pregnancy, serum beta human chorionic gonadotropin). Abnormality was determined by the investigator. Safety analysis population was used for analysis, which included all subjects who entered the extension study with at least 1 dose of study drug.

End point type

Primary

End point timeframe

1 year

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	66
Units: subjects	19	27	28

No statistical analyses for this end point

Primary: Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria

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End point title

Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria ^[3]

End point description

Number of subjects with data meeting the following criteria is given: supine systolic blood pressure (SBP)<90mmHg; standing SBP<90mmHg; supine diastolic blood pressure (DBP)<50mmHg; standing DBP<50mmHg; supine pulse rate<40 beats per minute (bpm); supine pulse rate>120bpm; standing pulse rate<40 bpm; standing pulse rate>140bpm; max increase from baseline in supine SBP>=30 mmHg; max increase from baseline in standing SBP>= 30mmHg; max increase from baseline in supine DBP>=20 mmHg; max increase from baseline in standing DBP>=20 mmHg; max decrease from baseline in supine SBP>=30mmHg; max decrease from baseline in standing SBP>=30mmHg; max decrease from baseline in supine DBP>=20mmHg; max decrease from baseline in standing DBP>=20mmHg. Analysis population included all subjects who entered the extension study with at least 1 dose of study drug. n in parentheses represents the number of subjects with data contributing to that category for each reporting arm.

End point type

Primary

End point timeframe

1 year

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	66
Units: subjects
Supine SBP <90 mmHg (n=49, 69, 65)	0	0	0
Standing SBP <90 mmHg (n=49, 69, 65)	0	1	0
Supine DBP <50 mmHg (n=49, 69, 65)	0	1	0
Standing DBP <50 mmHg (n=49, 69, 65)	0	1	0
Supine pulse rate <40 bpm (n=49, 69, 65)	0	0	0
Supine pulse rate >120 bpm (n=49, 69, 65)	0	0	0
Standing pulse rate <40 bpm (n=49, 69, 65)	0	0	0
Standing pulse rate >140 bpm (n=49, 69, 65)	0	0	0
Supine SBP increase >=30 mmHg (n=49, 69, 65)	3	1	6
Standing SBP increase >=30 mmHg (n=48, 69, 64)	1	6	4
Supine DBP increase >=20 mmHg (n=49, 69, 65)	4	2	6
Standing DBP increase >=20 mmHg (n=48, 69, 65)	3	8	2
Supine SBP decrease >=30 mmHg (n=49, 69, 65)	2	1	4
Standing SBP decrease >=30 mmHg (n=48, 69, 64)	0	1	2
Supine DBP decrease >=20 mmHg (n=49, 69, 65)	0	2	7
Standing DBP decrease >=20 mmHg (n=48, 69, 64)	1	4	6

No statistical analyses for this end point

Primary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria

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End point title

Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria ^[4]

End point description

Maximum absolute values and increases from baseline were summarized for PR interval (interval between start of ECG P wave and start of QRS complex corresponding to the time between onset of atrial depolarization and onset of ventricular depolarization), QRS complex (time from Q wave to end of S wave corresponding to ventricular depolarization), and QTcF interval (time from ECG Q wave to end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia’s formula). Number of subjects with data meeting the following criteria is given: PR >=300 msec; QRS >=140 msec; QTcF: 450 to <480 msec; QTcF: 480 to <500 msec; QTcF >=500 msec; PR increase >=25/50 percent; QRS increase >=50 percent; QTcF increase: 30 to <60 msec; QTcF increase >=60 msec. Analysis population included all subjects who entered the extension study with at least 1 dose of study drug. n in parentheses represents the number of subjects with data contributing to that category for each reporting arm.

End point type

Primary

End point timeframe

1 year

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	66
Units: subjects
PR interval >=300 msec (n=50, 69, 66)	0	0	0
QRS complex >=140 msec (50, 69, 66)	0	0	0
QTcF interval: 450 to <480 msec (n=50, 69, 66)	2	2	2
QTcF interval: 480 to <500 msec (n=50, 69, 66)	0	0	1
QTcF interval >=500 msec (n=50, 69, 66)	0	0	0
PR increase >=25/50 percent (n=50, 66, 66)	0	0	0
QRS increase >=50 percent (n=50, 66, 66)	0	0	0
QTcF increase: 30 to <60 msec (n=50, 66, 66)	3	5	4
QTcF increase >=60 msec (n=50, 66, 66)	0	0	0

No statistical analyses for this end point

Primary: Number of Subjects With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality)

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End point title

Number of Subjects With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality) ^[5]

End point description

Number of subjects 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. Safety analysis population was used for analysis, which included all subjects who entered the extension study with at least 1 dose of study medication.

End point type

Primary

End point timeframe

1 year

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	65
Units: subjects
WBC < 0.6*LLN	0	0	0
WBC > 1.5*ULN	1	0	1
ANC < 0.8*LLN	1	0	0
ANC > 1.2*ULN	3	4	7

No statistical analyses for this end point

Primary: Number of Subjects With Laboratory Test Abnormalities (Normal Baseline)

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End point title

Number of Subjects With Laboratory Test Abnormalities (Normal Baseline) ^[6]

End point description

End point type

Primary

End point timeframe

1 year

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	66
Units: subjects	13	22	23

No statistical analyses for this end point

Primary: Number of Subjects With Adverse Events Related to Extrapyramidal Symptoms by Severity

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End point title

Number of Subjects With Adverse Events Related to Extrapyramidal Symptoms by Severity ^[7]

End point 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 subject's usual function. Moderate means the AE interfered to some extent the subject's usual function. Severe means the AE interfered significantly with the subject's usual function.

End point type

Primary

End point timeframe

1 year

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	66
Units: subjects
Mild dystonia	0	1	0
Moderate dystonia	0	1	1
Severe dystonia	0	0	0
Mild akathisia	1	1	0
Moderate akathisia	0	1	3
Severe akathisia	0	0	1
Mild dyskinesia	0	2	4
Moderate dyskinesia	1	1	2
Severe dyskinesia	0	0	0

No statistical analyses for this end point

Primary: Number of Subjects in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category

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End point title

Number of Subjects in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category ^[8]

End point 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 subjects with any of the following behaviors occurring since last visit was summarized: completed suicide; suicide attempt; preparatory acts towards imminent suicidal behavior; suicidal ideation; self-injurious behavior, no suicidal intent. Safety analysis population was used for analysis, which included all subjects who entered the extension study with at least 1 dose of study medication. n in parentheses represents the number of subjects with data contributing to that category for each reporting arm.

End point type

Primary

End point timeframe

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)

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this end point.

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	51	71	66
Units: subjects
Day 1 (n=51, 71, 66)	0	1	1
Week 2 (n=51, 69, 64)	0	0	1
Week 4 (n=50, 66, 63)	0	1	1
Month 3 (n=42, 61, 57)	1	0	1
Month 6 (n=35, 37, 42)	1	0	1
Month 9 (n=26, 20, 29)	0	1	0
Month 12 (n=48, 69, 65)	6	0	3
Follow-up visit (n=23, 13, 26)	1	0	0

No statistical analyses for this end point

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Motor Score

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End point title

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

End point 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. Full analysis set (FAS) was used for analysis, which included all subjects who had a baseline efficacy evaluation and completed at least Week 2 visit with a valid UHDRS TMS score, and took >=1 dose of study medication. n in parentheses represents the number of subjects with data contributing to that category for each reporting arm.

End point type

Secondary

End point timeframe

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

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	50	70	62
Units: units on a scale
arithmetic mean (standard deviation)
Month 6 (n=33, 39, 40)	2.4 ± 7.21	3.5 ± 7.61	0.7 ± 7.43
Month 12 (n=15, 9, 22)	4.9 ± 10.17	3.3 ± 6.71	0.6 ± 8.24

No statistical analyses for this end point

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score

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End point title

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

End point 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. Full analysis set was used for analysis, which included all subjects who had a baseline efficacy evaluation and completed at least Week 2 visit with a valid UHDRS TMS score, and took >=1 dose of study drug. n in parentheses represents the number of subjects with data contributing to that category for each reporting arm.

End point type

Secondary

End point timeframe

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

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	50	70	62
Units: Units on a scale
arithmetic mean (standard deviation)
Month 6 (n=33, 39, 40)	0.1 ± 3.12	1.3 ± 3.97	1.4 ± 4.14
Month 12 (n=15, 9, 22)	0.1 ± 4.92	0.8 ± 1.64	0.7 ± 3.51

No statistical analyses for this end point

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

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End point title

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

End point description

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 by interviewing the subject. 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 subject’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. Full analysis set was used for analysis, which included all subjects who had a baseline efficacy evaluation and completed at least Week 2 visit with a valid UHDRS TMS score, and took >=1 dose of study drug. n in parentheses represents the number of subjects with data contributing to that category for each reporting arm.

End point type

Secondary

End point timeframe

Month 6 and Month 12

End point values	20 mg PF-02545920	5 mg PF-02545920 Titration up to 20 mg	Placebo and Titration up to 20 mg PF-02545920
Number of subjects analysed	50	70	62
Units: units on a scale
arithmetic mean (standard deviation)
Month 6 (n=33, 39, 41)	3.9 ± 1.04	4.2 ± 1.03	3.7 ± 1.19
Month 12 (n=15, 9, 22)	3.5 ± 1.30	4.6 ± 1.13	4.0 ± 1.21

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

1 year

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

20 mg PF-02545920

Reporting 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.

Reporting group title

5 mg PF-02545920 Titration up to 20 mg

Reporting group description

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).

Reporting group title

Placebo and Titration up to 20 mg PF-02545920

Reporting group description

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).

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
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 51 (13.73%)	9 / 71 (12.68%)	5 / 66 (7.58%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
General disorders and administration site conditions
Complication associated with device
subjects affected / exposed	1 / 51 (1.96%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Prostatomegaly
subjects affected / exposed	1 / 51 (1.96%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 51 (0.00%)	0 / 71 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	1 / 51 (1.96%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Panic attack
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 51 (1.96%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Cervical vertebral fracture
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Huntington's disease
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Chorea
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyperkinesia
subjects affected / exposed	2 / 51 (3.92%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Dysphagia
subjects affected / exposed	0 / 51 (0.00%)	0 / 71 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 51 (0.00%)	0 / 71 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 51 (0.00%)	0 / 71 (0.00%)	1 / 66 (1.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Urinary tract disorder
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 51 (1.96%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	1 / 51 (1.96%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 51 (1.96%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 51 (0.00%)	1 / 71 (1.41%)	0 / 66 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-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
Total subjects affected by non serious adverse events
subjects affected / exposed	32 / 51 (62.75%)	53 / 71 (74.65%)	54 / 66 (81.82%)
Investigations
Weight decreased
subjects affected / exposed	3 / 51 (5.88%)	7 / 71 (9.86%)	11 / 66 (16.67%)
occurrences all number	3	7	11
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	6 / 51 (11.76%)	15 / 71 (21.13%)	8 / 66 (12.12%)
occurrences all number	10	20	11
Nervous system disorders
Akathisia
subjects affected / exposed	1 / 51 (1.96%)	2 / 71 (2.82%)	4 / 66 (6.06%)
occurrences all number	1	4	6
Chorea
subjects affected / exposed	11 / 51 (21.57%)	11 / 71 (15.49%)	14 / 66 (21.21%)
occurrences all number	12	15	14
Dizziness
subjects affected / exposed	0 / 51 (0.00%)	9 / 71 (12.68%)	5 / 66 (7.58%)
occurrences all number	0	15	5
Dyskinesia
subjects affected / exposed	1 / 51 (1.96%)	3 / 71 (4.23%)	6 / 66 (9.09%)
occurrences all number	2	4	6
Headache
subjects affected / exposed	1 / 51 (1.96%)	5 / 71 (7.04%)	3 / 66 (4.55%)
occurrences all number	1	5	4
Hyperkinesia
subjects affected / exposed	7 / 51 (13.73%)	0 / 71 (0.00%)	2 / 66 (3.03%)
occurrences all number	11	0	3
Sedation
subjects affected / exposed	1 / 51 (1.96%)	2 / 71 (2.82%)	5 / 66 (7.58%)
occurrences all number	1	2	9
Somnolence
subjects affected / exposed	1 / 51 (1.96%)	4 / 71 (5.63%)	9 / 66 (13.64%)
occurrences all number	1	6	10
General disorders and administration site conditions
Fatigue
subjects affected / exposed	2 / 51 (3.92%)	9 / 71 (12.68%)	9 / 66 (13.64%)
occurrences all number	2	13	9
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 51 (3.92%)	6 / 71 (8.45%)	4 / 66 (6.06%)
occurrences all number	2	10	7
Dysphagia
subjects affected / exposed	2 / 51 (3.92%)	3 / 71 (4.23%)	4 / 66 (6.06%)
occurrences all number	2	4	4
Nausea
subjects affected / exposed	2 / 51 (3.92%)	9 / 71 (12.68%)	8 / 66 (12.12%)
occurrences all number	2	14	9
Vomiting
subjects affected / exposed	1 / 51 (1.96%)	5 / 71 (7.04%)	3 / 66 (4.55%)
occurrences all number	2	5	9
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 51 (3.92%)	5 / 71 (7.04%)	7 / 66 (10.61%)
occurrences all number	2	6	8
Depression
subjects affected / exposed	3 / 51 (5.88%)	3 / 71 (4.23%)	5 / 66 (7.58%)
occurrences all number	3	3	5
Insomnia
subjects affected / exposed	2 / 51 (3.92%)	4 / 71 (5.63%)	9 / 66 (13.64%)
occurrences all number	2	5	11
Restlessness
subjects affected / exposed	1 / 51 (1.96%)	2 / 71 (2.82%)	5 / 66 (7.58%)
occurrences all number	1	4	6
Sleep disorder
subjects affected / exposed	3 / 51 (5.88%)	3 / 71 (4.23%)	2 / 66 (3.03%)
occurrences all number	3	3	2
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	3 / 51 (5.88%)	6 / 71 (8.45%)	4 / 66 (6.06%)
occurrences all number	3	6	4
Muscle spasms
subjects affected / exposed	3 / 51 (5.88%)	0 / 71 (0.00%)	0 / 66 (0.00%)
occurrences all number	4	0	0
Infections and infestations
Viral upper respiratory tract infection
subjects affected / exposed	4 / 51 (7.84%)	3 / 71 (4.23%)	7 / 66 (10.61%)
occurrences all number	5	3	9

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

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.

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Clinical trials

Clinical Trial Results:
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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects With Treatment-Emergent Adverse Events and Serious Adverse Events

Primary: Number of Subjects With Treatment-Emergent Adverse Events and Serious Adverse Events

Primary: Number of Subjects With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Laboratory Test Abnormalities (Normal Baseline)

Primary: Number of Subjects With Laboratory Test Abnormalities (Normal Baseline)

Primary: Number of Subjects With Adverse Events Related to Extrapyramidal Symptoms by Severity

Primary: Number of Subjects With Adverse Events Related to Extrapyramidal Symptoms by Severity

Primary: Number of Subjects in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category

Primary: Number of Subjects in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Motor Score

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Motor Score

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects With Treatment-Emergent Adverse Events and Serious Adverse Events

Primary: Number of Subjects With Treatment-Emergent Adverse Events and Serious Adverse Events

Primary: Number of Subjects With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria

Primary: Number of Subjects With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality)

Primary: Number of Subjects With Laboratory Test Abnormalities (Normal Baseline)

Primary: Number of Subjects With Laboratory Test Abnormalities (Normal Baseline)

Primary: Number of Subjects With Adverse Events Related to Extrapyramidal Symptoms by Severity

Primary: Number of Subjects With Adverse Events Related to Extrapyramidal Symptoms by Severity

Primary: Number of Subjects in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category

Primary: Number of Subjects in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Motor Score

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Motor Score

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score

Secondary: Change From Baseline in Unified Huntington’s Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
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