Fragile X Syndrome
Conditions
Keywords
fragile X syndrome, irritability, behavior problems
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.
Interventions
DRUGSTX209
Variable dose from 1 mg bid to 10 mg tid, Capsule, Oral, 4 weeks
DRUGPlacebo
variable dose (same flexible dose titration protocol), bid to tid, capsule, Oral, 4 weeks
Sponsors
Seaside Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 40 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| STX209 STX209 Variable dose, 1mg bid to 10mg tid, oral capsules, 4weeks | 30 |
| Placebo placebo variable dose (same flexible dose titration protocol) bid to tid, oral, 4weeks | 33 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Placebo Then STX209 | Adverse Event | 2 | 0 |
| Placebo Then STX209 | Protocol Violation | 0 | 1 |
| STX209 Then Placebo | Adverse Event | 1 | 0 |
| STX209 Then Placebo | Lost to Follow-up | 0 | 1 |
| STX209 Then Placebo | unable to return due to travel | 0 | 1 |
| STX209 Then Placebo | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | STX209 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 24 Participants | 22 Participants | 46 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 17 Participants |
| Age Continuous | 13.9 years STANDARD_DEVIATION 6.39 | 14.2 years STANDARD_DEVIATION 7.29 | 14.1 years STANDARD_DEVIATION 6.78 |
| Region of Enrollment United States | 33 participants | 30 participants | 63 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 27 Participants | 28 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 42 / 63 | 31 / 63 |
| serious Total, serious adverse events | 1 / 63 | 0 / 63 |
Outcome results
Primary
Aberrant Behavior Checklist Irritability Subscore
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| STX209:Placebo | Aberrant Behavior Checklist Irritability Subscore | -5.1 Points on a scale | Standard Error 0.95 |
| Placebo:STX209 | Aberrant Behavior Checklist Irritability Subscore | -5.3 Points on a scale | Standard Error 0.95 |
p-value: 0.05ANCOVA
Post Hoc
ABC-FXS Social Avoidance Subscore
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| STX209:Placebo | ABC-FXS Social Avoidance Subscore | -1.2 Points on a scale | Standard Error 0.24 |
| Placebo:STX209 | ABC-FXS Social Avoidance Subscore | -0.1 Points on a scale | Standard Error 0.24 |
p-value: 0.008ANCOVA