First-HD: First Time Use of SD-809 in Huntington Disease

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01795859
• Collaborator: (none)
• Enrollment: 90
• Locations: 43
• Arms: 2
• Actual Duration (Months): 16
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether SD-809 tablets are effective in the treatment of chorea associated with Huntington's Disease.

Condition or Disease	Intervention/Treatment	Phase
Chorea	Drug: SD-809; Drug: Placebo	Phase 3

Detailed Description

This is a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety and tolerability of SD-809 for the treatment of chorea associated with Huntington's Disease. Approximately 90 subjects will be randomized (1:1) into the study, with approximately 45 subjects receiving SD-809 and 45 subjects receiving placebo. The study will be conducted at approximately 30 centers in the U.S. and Canada.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-Blind, Placebo-Controlled Study of SD-809 Extended Release for the Treatment of Chorea Associated With Huntington Disease
• Actual Study Start Date: Aug 5, 2013
• Actual Primary Completion Date: Dec 5, 2014
• Actual Study Completion Date: Dec 5, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SD-809 ER Tablets SD-809 ER tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white). All are administered three times a day, with the 6 mg final dose is placebo.	Drug: SD-809; SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).; Other Names: deutetrabenazine ; Drug: Placebo; Placebo tablets are identical in appearance to SD-809 tablets.
Experimental: SD-809 Tablets SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white). All are administered three times a day, with the 6 mg final dose is placebo.	Drug: SD-809; SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).; Other Names: deutetrabenazine ; Drug: Placebo; Placebo tablets are identical in appearance to SD-809 tablets.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12 [Screening, Day 0, Weeks 9, 12]

   Total TMC score is a sum of chorea scores which range 0-28, with a decrease indicating improvement in chorea

Secondary Outcome Measures

1. Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC) [12 weeks]

   A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved

2. Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC) [12 weeks]

   A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved. The clinician was asked to comment about the subject.

3. Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12 [Baseline, 12 weeks]

   Change in the Short Form 36 Health Survey (SF-36) physical functioning score (based on items 3a to 3j) from Baseline to Week 12. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

4. Change in Berg Balance Test (BBT) [Baseline, 12 weeks]

   The Berg Balance Test (BBT) is a 14-item assessment of sitting, standing, transferring, and turning. Each task ranging from standing up from a sitting position, to standing on one foot each task is given a score of zero (unable) to four (independent), and the final measure is the sum of all of the scores.The scale range, which is 0-56, with higher scores indicating better balance/lower fall risk.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is at least 18 years of age or the age of majority (whichever is older) at Screening.

• Subject has been diagnosed with manifest HD

• Subject is able to swallow study medication whole.

• Female subjects of childbearing potential agree to use an acceptable method of contraception from screening through study completion.

• The subject has a reliable caregiver who interacts with the patient on a daily basis, oversees study drug administration, assures attendance at study visits and participates in evaluations, as required.

• Subject is able to ambulate without assistance for at least 20 yards (Note: The use of assistive devices (i.e., walker, cane) is permitted during ambulation).

Exclusion Criteria:

• Subject has a serious untreated or under-treated psychiatric illness, such as depression, at Screening or Baseline.

• Subject has active suicidal ideation at Screening or Baseline.

• Subject has history of suicidal behavior at Screening or Baseline:

• Subject has evidence for depression at Screening or Baseline.

• Subject has an unstable or serious medical or psychiatric illness at Screening or Baseline.

• Subject has been recently exposed to tetrabenazine.

• Subject has received any of the following concomitant medications within 30 days of

Screening or Baseline:

• Antipsychotics

• Metoclopramide

• Monoamine oxidase inhibitors (MAOI)

• Levodopa or dopamine agonists

• Reserpine

• Amantadine

• Memantine

• Subject has significantly impaired swallowing function at Screening.

• Subject has significantly impaired speaking at Screening.

• Subject requires treatment with drugs known to prolong the QT interval.

• Subject has a prolonged QT interval on 12-lead ECG at Screening.

• Subject has evidence of hepatic impairment at Screening.

• Subject has evidence of significant renal impairment at Screening.

• Subject has known allergy to any of the components of study medication.

• Subject has participated in an investigational drug or device trial within 30 days (or 5 drug half-lives) of Screening, whichever is longer.

• Subject is pregnant or breast-feeding at Screening or Baseline.

• Subject acknowledges present use of illicit drugs at Screening.

• Subject has a history of alcohol or substance abuse in the previous 12 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 057	Birmingham	Alabama	United States
2	Teva Investigational Site 038	Phoenix	Arizona	United States
3	Teva Investigational Site 298	Fayetteville	Arkansas	United States
4	Teva Investigational Site 050	Los Angeles	California	United States
5	Teva Investigational Site 052	Englewood	Colorado	United States
6	Teva Investigational Site 333	Washington, D.C.	District of Columbia	United States
7	Teva Investigational Site 196	Boca Raton	Florida	United States
8	Teva Investigational Site 160	Gainesville	Florida	United States
9	Teva Investigational Site 014	Miami	Florida	United States
10	Teva Investigational Site 032	Atlanta	Georgia	United States
11	Teva Investigational Site 045	Indianapolis	Indiana	United States
12	Teva Investigational Site 024	Iowa City	Iowa	United States
13	Teva Investigational Site 029	Kansas City	Kansas	United States
14	Teva Investigational Site 083	Wichita	Kansas	United States
15	Teva Investigational Site 087	Louisville	Kentucky	United States
16	Teva Investigational Site 028	Baltimore	Maryland	United States
17	Teva Investigational Site 040	Boston	Massachusetts	United States
18	Teva Investigational Site 027	Saint Louis	Missouri	United States
19	Teva Investigational Site 194	Las Vegas	Nevada	United States
20	Teva Investigational Site 328	Camden	New Jersey	United States
21	Teva Investigational Site 026	New Brunswick	New Jersey	United States
22	Teva Investigational Site 037	Albany	New York	United States
23	Teva Investigational Site 002	New York	New York	United States
24	Teva Investigational Site 342	Patchogue	New York	United States
25	Teva Investigational Site 119	Durham	North Carolina	United States
26	Teva Investigational Site 089	Cincinnati	Ohio	United States
27	Teva Investigational Site 020	Columbus	Ohio	United States
28	Teva Investigational Site 093	Toledo	Ohio	United States
29	Teva Investigational Site 341	Tulsa	Oklahoma	United States
30	Teva Investigational Site 031	Nashville	Tennessee	United States
31	Teva Investigational Site 007	Houston	Texas	United States
32	Teva Investigational Site 199	Houston	Texas	United States
33	Teva Investigational Site 100	Salt Lake City	Utah	United States
34	Teva Investigational Site 137	Burlington	Vermont	United States
35	Teva Investigational Site 220	Kirkland	Washington	United States
36	Teva Investigational Site 096	Seattle	Washington	United States
37	Teva Investigational Site 104	Milwaukee	Wisconsin	United States
38	Teva Investigational Site 144	Kew Vic		Australia
39	Teva Investigational Site 054	Sydney		Australia
40	Teva Investigational Site 098	Montreal		Canada
41	Teva Investigational Site 300	North York		Canada
42	Teva Investigational Site 231	Ottawa		Canada
43	Teva Investigational Site 300	Ottawa		Canada

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT01795859
• Other Study ID Numbers: SD-809-C-15
• First Posted: Feb 21, 2013
• Last Update Posted: Sep 20, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: Huntington disease; Chorea; Tetrabenazine
• Additional relevant MeSH terms: Huntington Disease; Chorea

Study Results

Participant Flow

Recruitment Details	A total of 90 subjects were randomized 1:1 to receive either SD-809 or placebo. All subjects were assessed for capacity to provide informed consent and written informed consent was obtained appropriately

Arm/Group Title	SD-809 Tablets	SD-809 Placebo
Arm/Group Description	SD-809: SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).	Placebo: Placebo tablets are identical in appearance to SD-809 tablets.
Period Title: Overall Study
STARTED	45	45
COMPLETED	44	43
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	SD-809 Tablets	SD-809 Placebo	Total
Arm/Group Description	SD-809: SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).	Placebo: Placebo tablets are identical in appearance to SD-809 tablets.	Total of all reporting groups
Overall Participants	45	45	90
Age, Customized (participants) [Mean (Standard Deviation) ]
SD-809	55.4 (10.32) 123.1%	52.1 (13.36) 115.8%	53.7 (11.98) 59.7%
Sex: Female, Male (Count of Participants)
Female	23 51.1%	17 37.8%	40 44.4%
Male	22 48.9%	28 62.2%	50 55.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	5 11.1%	5 5.6%
White	45 100%	38 84.4%	83 92.2%
More than one race	0 0%	2 4.4%	2 2.2%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12
Description	Total TMC score is a sum of chorea scores which range 0-28, with a decrease indicating improvement in chorea
Time Frame	Screening, Day 0, Weeks 9, 12

Outcome Measure Data

Analysis Population Description

The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one postbaseline assessment. For subjects who missed both Week 9 or Week 12 scores, the last available assessment was used

Arm/Group Title	SD-809 Tablets	SD-809 Placebo
Arm/Group Description	SD-809: SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).	Placebo: Placebo tablets are identical in appearance to SD-809 tablets.
Measure Participants	45	45
Least Squares Mean (Standard Deviation) [Units on a scale]	-4.42 (2.953)	-1.93 (2.666)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809 Tablets, SD-809 Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-2.49
	Confidence Interval	(2-Sided) 95%; -3.69 to -1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC)
Description	A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one post baseline assessment.

Arm/Group Title	SD-809 Tablets	SD-809 Placebo
Arm/Group Description	SD-809: SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).	Placebo: Placebo tablets are identical in appearance to SD-809 tablets.
Measure Participants	45	45
Count of Participants [Participants]	23 51.1%	9 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809 Tablets, SD-809 Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Difference of proportions
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	31.1
	Confidence Interval	(2-Sided) 95%; 12.4 to 49.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC)
Description	A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved. The clinician was asked to comment about the subject.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one post-baseline assessment.

Arm/Group Title	SD-809 Tablets	SD-809 Placebo
Arm/Group Description	SD-809: SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).	Placebo: Placebo tablets are identical in appearance to SD-809 tablets.
Measure Participants	45	45
Count of Participants [Participants]	19 42.2%	6 13.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809 Tablets, SD-809 Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	Difference of proportions
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	28.9
	Confidence Interval	(2-Sided) 95%; 11.4 to 46.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12
Description	Change in the Short Form 36 Health Survey (SF-36) physical functioning score (based on items 3a to 3j) from Baseline to Week 12. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The modified intent to treat (mITT) population will include all subjects in the ITT population who were randomized to treatment and received study drug. For subjects with missing value at Week 12, the last available assessment was used

Arm/Group Title	SD-809 Tablets	SD-809 Placebo
Arm/Group Description	SD-809: SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).	Placebo: Placebo tablets are identical in appearance to SD-809 tablets.
Measure Participants	45	43
Mean (Standard Deviation) [units on a scale]	0.74 (9.773)	-3.61 (9.669)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809 Tablets, SD-809 Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0308
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	4.34
	Confidence Interval	(2-Sided) 95%; 0.41 to 8.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change in Berg Balance Test (BBT)
Description	The Berg Balance Test (BBT) is a 14-item assessment of sitting, standing, transferring, and turning. Each task ranging from standing up from a sitting position, to standing on one foot each task is given a score of zero (unable) to four (independent), and the final measure is the sum of all of the scores.The scale range, which is 0-56, with higher scores indicating better balance/lower fall risk.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

The Modified ITT (mITT) Population was defined as all subjects in the ITT Population who received study drug and had at least one postbaseline assessment. For subjects with missing value at Week 12, the last available assessment was used

Arm/Group Title	SD-809 Tablets	SD-809 Placebo
Arm/Group Description	SD-809: SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).	Placebo: Placebo tablets are identical in appearance to SD-809 tablets.
Measure Participants	45	45
Least Squares Mean (Standard Deviation) [units on a scale]	2.2 (3.47)	1.3 (4.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SD-809 Tablets, SD-809 Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1415
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.3 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Placebo		SD-809
Arm/Group Description	Placebo		SD-809
All Cause Mortality
	Placebo		SD-809
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		SD-809
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/45 (2.2%)		1/45 (2.2%)
Hepatobiliary disorders
Cholecystitis chronic	0/45 (0%)	0	1/45 (2.2%)	1
Psychiatric disorders
Agitated depression	0/45 (0%)	0	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/45 (2.2%)	1	0/45 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		SD-809
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/45 (46.7%)		18/45 (40%)
Gastrointestinal disorders
Diarrhoea	0/45 (0%)	0	4/45 (8.9%)	4
Dry mouth	3/45 (6.7%)	3	4/45 (8.9%)	4
Vomiting	3/45 (6.7%)	3	0/45 (0%)	0
General disorders
Fatigue	2/45 (4.4%)	2	3/45 (6.7%)	4
Irritability	6/45 (13.3%)	6	3/45 (6.7%)	3
Injury, poisoning and procedural complications
Fall	4/45 (8.9%)	6	2/45 (4.4%)	4
Nervous system disorders
Dizziness	4/45 (8.9%)	4	2/45 (4.4%)	2
Headache	3/45 (6.7%)	3	0/45 (0%)	0
Somnolence	2/45 (4.4%)	2	5/45 (11.1%)	6
Psychiatric disorders
Depression	3/45 (6.7%)	3	1/45 (2.2%)	1
Insomnia	2/45 (4.4%)	2	3/45 (6.7%)	3
Sleep disorder	3/45 (6.7%)	3	0/45 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.