Safety, Tolerability and Efficacy Study of STX209 in Subjects With Fragile X Syndrome

• Sponsor: Seaside Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00788073
• Collaborator: (none)
• Enrollment: 63
• Locations: 12
• Arms: 2
• Duration (Months): 17.9
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The study objective is to explore the efficacy, safety and tolerability of STX209 for treatment of irritability in subjects with FSX. We hypothesize that STX209 will improve irritability and other typical problem behaviors associated with fragile X syndrome. We also hypothesize that STX209 will be safe and well tolerated.

Condition or Disease	Intervention/Treatment	Phase
Fragile X Syndrome	Drug: STX209; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled, Crossover, Flexible-Dose Evaluation of the Efficacy, Safety and Tolerability of STX209 in the Treatment of Irritability in Subjects With Fragile X Syndrome
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: STX209 STX209 variable dose from 1mg bid to 10mg tid, capsule, oral, 4 weeks	Drug: STX209; Variable dose from 1 mg bid to 10 mg tid, Capsule, Oral, 4 weeks; Other Names: arbaclofen
Placebo Comparator: Placebo variable dose (same flexible dose titration protocol), bid to tid, capsule, Oral, 4 weeks	Drug: Placebo; variable dose (same flexible dose titration protocol), bid to tid, capsule, Oral, 4 weeks

Outcome Measures

Primary Outcome Measures

1. Aberrant Behavior Checklist Irritability Subscore [After 4 weeks of treatment]

   The Aberrant Behavior Checklist-Community Edition (ABC-C) is a 58-item questionnaire composed of five different independent subscales. The questionnaire is completed by the parent/caregiver and lists aberrant behaviors and asks about the severity of the problem. ABC-Irritability is one of the subscales and comprises of 15 items. Minimum score is 0, maximum is 45. A decreased score indicates few aberrant behaviors and clinical improvement. The entire ABC-C assessment is administered at baseline and then at the end of each Intervention Period (4 weeks after Baseline).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female subjects 12 to 40 years of age eventually expanding to 6 years of age

• Molecular documentation of the fragile X mutation.

• Clinical Global Impression - Severity (CGI-S) rating for problem behavior of moderate or higher at screening and at Visit 1

• An Aberrant Behavior Checklist (ABC-C) Irritability Subscale score >12 and at least 3 items on the Irritability Subscale rated at least moderate or above.

• Current treatment with no more than three psychoactive medications, including anti-epileptics.

• Current pharmacological treatment regimen has been stable for at least 4 weeks.

Exclusion Criteria:

• Subjects with a history of seizure disorder who are not currently receiving treatment with antiepileptics.

• Subjects with any condition, including alcohol and drug abuse, which might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. This includes, but is not limited to impairment of renal function, evidence or history of malignancy or any significant hematological, endocrine, cardiovascular, respiratory, hepatic, or gastrointestinal disease.

• Subjects who plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.

• Subjects who are currently receiving treatment with racemic baclofen.

• Subjects currently treated with vigabatrin or tiagabine.

• Subjects taking another investigational drug currently or within the last 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southwest Autism Research & Resource Center	Phoenix	Arizona	United States	85006
2	University of California-Los Angeles Neuropsychiatric Institute	Los Angeles	California	United States	90024
3	M.I.N.D. Institute	Sacramento	California	United States	95817
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
6	Children's Hospital Boston	Boston	Massachusetts	United States	02115
7	NYS Institute for Basic Research in Developmental Disabilities	Staten Island	New York	United States	10314
8	University of North Carolina Neurosciences Hospital	Chapel Hill	North Carolina	United States	27514
9	Suburban Research Associates	Media	Pennsylvania	United States	19063
10	Vanderbilt Kennedy Center	Nashville	Tennessee	United States	37203
11	Red Oaks Psychiatry Associates, P.A.	Houston	Texas	United States	77090
12	Seattle Children's Hospital	Seattle	Washington	United States	98101

Sponsors and Collaborators

• Seaside Therapeutics, Inc.

Investigators

• Principal Investigator: Elizabeth Berry-Kravis, MD, PhD, Rush University Medical Center
• Principal Investigator: Randi Hagerman, MD, M.I.N.D. Institute
• Principal Investigator: Craig Erikson, MD, Riley Hospital for Children
• Principal Investigator: Bryan King, MD, PhD, Seattle Children's Hospital
• Principal Investigator: James McCracken, MD, University of California, Los Angeles
• Principal Investigator: Jonathan Picker, MBChB, PhD, Boston Children's Hospital
• Principal Investigator: Linmarie Sikich, MD, University of North Carolina Neurosciences Hospital
• Principal Investigator: Jeremy Veenstra-VanderWeele, MD, Vanderbilt Kennedy Center
• Principal Investigator: Ted Brown, MD, PhD, NYS institute for Basic Research in Developmental Disabilities
• Principal Investigator: Lawrence Ginsberg, MD, Red Oaks Psychiatry Associates, PA
• Principal Investigator: Shivkumar Hatti, MD, Suburban Research Associates
• Principal Investigator: Raun Melmed, MD, Southwest Autism Research & Resource Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Seaside Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT00788073
• Other Study ID Numbers: 22001
• First Posted: Nov 10, 2008
• Last Update Posted: May 6, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Seaside Therapeutics, Inc.: fragile X syndrome; irritability; behavior problems
• Additional relevant MeSH terms: Fragile X Syndrome; Syndrome

Study Results

Participant Flow

Arm/Group Title	STX209:Placebo	Placebo:STX209
Arm/Group Description	First Intervention=STX209 (STX209 variable dose from 1mg bid to 10mg tid, capsule, oral) Second Intervention=Placebo (Placebo variable dose (same flexible dose titration protocol) bid to tid, oral) Study Design: Placebo-controlled, Crossover study. First Intervention(28 Days)-> Withdrawal(14 Days) -> Washout(7 Days)-> Withdrawal (14 Days) Participants received all interventions.	First Intervention=Placebo (Placebo variable dose (same flexible dose titration protocol) bid to tid, oral) Second Intervention=STX209 (STX209 variable dose from 1mg bid to 10mg tid, capsule, oral) Study Design: Placebo-controlled, Crossover study. First Intervention(28 Days)-> Withdrawal(14 Days) -> Washout(7 Days)-> Withdrawal (14 Days) Participants received all interventions.
Period Title: STX209 Then Placebo
STARTED	30	33
COMPLETED	29	30
NOT COMPLETED	1	3
Period Title: STX209 Then Placebo
STARTED	29	30
COMPLETED	27	29
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	STX209	Placebo	Total
Arm/Group Description	STX209 Variable dose, 1mg bid to 10mg tid, oral capsules, 4weeks	placebo variable dose (same flexible dose titration protocol) bid to tid, oral, 4weeks	Total of all reporting groups
Overall Participants	30	33	63
Age (Count of Participants)
<=18 years	22 73.3%	24 72.7%	46 73%
Between 18 and 65 years	8 26.7%	9 27.3%	17 27%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.2 (7.29)	13.9 (6.39)	14.1 (6.78)
Sex: Female, Male (Count of Participants)
Female	2 6.7%	6 18.2%	8 12.7%
Male	28 93.3%	27 81.8%	55 87.3%
Region of Enrollment (participants) [Number]
United States	30 100%	33 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Aberrant Behavior Checklist Irritability Subscore
Description	The Aberrant Behavior Checklist-Community Edition (ABC-C) is a 58-item questionnaire composed of five different independent subscales. The questionnaire is completed by the parent/caregiver and lists aberrant behaviors and asks about the severity of the problem. ABC-Irritability is one of the subscales and comprises of 15 items. Minimum score is 0, maximum is 45. A decreased score indicates few aberrant behaviors and clinical improvement. The entire ABC-C assessment is administered at baseline and then at the end of each Intervention Period (4 weeks after Baseline).
Time Frame	After 4 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	STX209:Placebo	Placebo:STX209
Arm/Group Description	First Intervention=STX209 (STX209 variable dose from 1mg bid to 10mg tid, capsule, oral) Second Intervention=Placebo (Placebo variable dose (same flexible dose titration protocol) bid to tid, oral) Study Design: Placebo-controlled, Crossover study. First Intervention(28 Days)-> Withdrawal(14 Days) -> Washout(7 Days)-> Withdrawal (14 Days) Participants received all interventions.	First Intervention=Placebo (Placebo variable dose (same flexible dose titration protocol) bid to tid, oral) Second Intervention=STX209 (STX209 variable dose from 1mg bid to 10mg tid, capsule, oral) Study Design: Placebo-controlled, Crossover study. First Intervention(28 Days)-> Withdrawal(14 Days) -> Washout(7 Days)-> Withdrawal (14 Days) Participants received all interventions.
Measure Participants	63	63
Least Squares Mean (Standard Error) [Points on a scale]	-5.1 (0.95)	-5.3 (0.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	STX209:Placebo, Placebo:STX209
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Post-Hoc Outcome

Title	ABC-FXS Social Avoidance Subscore
Description	After completion of the study, but during data analysis, the ABC-C assessment was independently re-validated in Fragile X Syndrome subjects. The subscales were re-factored into a Fragile-X Syndrome specific ABC-C (ABC-FX). The ABC-FX contains the same 58 questions as the original ABC-C but there are six subscales. One of the subscales is Social Avoidance, which consists of 4 items. Minimum score is 0, maximum is 12. A decreased score indicates fewer social avoidant behaviors. A post-hoc analysis was performed from the study data examining the social avoidance subscale of the ABC-FX.
Time Frame	4 week treatment period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	STX209:Placebo	Placebo:STX209
Arm/Group Description	First Intervention=STX209 (STX209 variable dose from 1mg bid to 10mg tid, capsule, oral) Second Intervention=Placebo (Placebo variable dose (same flexible dose titration protocol) bid to tid, oral) Study Design: Placebo-controlled, Crossover study. First Intervention(28 Days)-> Withdrawal(14 Days) -> Washout(7 Days)-> Withdrawal (14 Days) Participants received all interventions.	First Intervention=Placebo (Placebo variable dose (same flexible dose titration protocol) bid to tid, oral) Second Intervention=STX209 (STX209 variable dose from 1mg bid to 10mg tid, capsule, oral) Study Design: Placebo-controlled, Crossover study. First Intervention(28 Days)-> Withdrawal(14 Days) -> Washout(7 Days)-> Withdrawal (14 Days) Participants received all interventions.
Measure Participants	63	63
Least Squares Mean (Standard Error) [Points on a scale]	-1.2 (0.24)	-0.1 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	STX209:Placebo, Placebo:STX209
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.0
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	STX209		Placebo
Arm/Group Description	STX209 variable dose from 1mg bid to 10mg tid, capsule, oral, 4 weeks		variable dose (same flexible dose titration protocol), bid to tid, capsule, Oral, 4 weeks
All Cause Mortality
	STX209		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	STX209		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/63 (1.6%)		0/63 (0%)
Psychiatric disorders
increased irritability	1/63 (1.6%)	1	0/63 (0%)	0
Other (Not Including Serious) Adverse Events
	STX209		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/63 (66.7%)		31/63 (49.2%)
Gastrointestinal disorders
diarrhea	3/63 (4.8%)	3	5/63 (7.9%)	5
vomiting	4/63 (6.3%)	4	1/63 (1.6%)	1
General disorders
fatigue	4/63 (6.3%)	4	1/63 (1.6%)	1
Infections and infestations
nasopharyngitis	2/63 (3.2%)	2	6/63 (9.5%)	6
Metabolism and nutrition disorders
increased appetite	4/63 (6.3%)	4	2/63 (3.2%)	2
Nervous system disorders
headache	5/63 (7.9%)	5	1/63 (1.6%)	1
sedation	5/63 (7.9%)	5	1/63 (1.6%)	1
Psychiatric disorders
irritability	4/63 (6.3%)	4	4/63 (6.3%)	4
aggression	3/63 (4.8%)	3	4/63 (6.3%)	4
Respiratory, thoracic and mediastinal disorders
upper respiratory tract infection	8/63 (12.7%)	8	6/63 (9.5%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Seaside Therapeutics agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.