A 2-Period Crossover Study of BPN14770 in Adults Males With Fragile X Syndrome
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|ClinicalTrials.gov Identifier: NCT03569631|
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : June 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Fragile X Syndrome FXS Fra(X) Syndrome||Drug: BPN14770 Drug: Placebo||Phase 2|
A total of 30 subjects will be enrolled. The study consists of a screening period of up to 28 days prior to initial treatment, followed by two double-blind treatment periods, each 12 weeks long. A final follow-up visit or phone contact for safety is planned one week after the conclusion of Period 2.
Eligible subjects will be randomized in a blinded, balanced (1:1) fashion to receive either 25 mg BPN14770 capsules or matching placebo capsules during Period 1, followed by the opposite treatment during Period 2. One capsule will be taken twice daily during both double-blind periods.
Subjects will return to the clinic at the end of Weeks 2, 6, and 12 of each study period. Cognitive and behavioral evaluations will be repeated at Weeks 6 and 12 of each Period. Additionally, patients will be monitored for adverse events via a telephone call at the end of Week 1 of each Period, and one week following completion of Period 2 or following early discontinuation.
During clinic visits, adverse effects will be assessed, and laboratory measures, vital signs, and ECGs will be performed. Suicidality risk will also be evaluated at each clinic visit; if a concern is detected, the subject will be referred for further evaluation and treatment. Cognitive and behavioral assessments will be performed during each clinic visit. Pharmacodynamic measures of CNS function will be obtained to evaluated effects of the drug in the brain. Pharmacokinetic samples will be collected to confirm that study drug is present and to estimate plasma exposure at Week 12 of each Period.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study of BPN14770 in Adult Males With Fragile X Syndrome|
|Actual Study Start Date :||June 25, 2018|
|Estimated Primary Completion Date :||August 31, 2019|
|Estimated Study Completion Date :||August 31, 2019|
25mg BPN14770 capsules, one capsule taken twice daily for 12 weeks
25 mg BPN14770 capsules
Placebo Comparator: Placebo
Matching placebo capsules, one capsule taken twice daily for 12 weeks
Placebo capsules to mimic 25 mg BPN14770 capsules
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: up to 24 weeks ]Number of subjects with treatment-related adverse events as assessed by MedDRA
- NIH-TCB: NIH Toolbox Cognitive Battery for Intellectual Disabilities [ Time Frame: Change from Baseline to Week 6 and Week 12 of each Period for each of 7 assessments ]A set of 7 cognition assessments administered on an iPad
- KiTAP Test of Attentional Performance [ Time Frame: Change from Baseline to Week 6 and Week 12 of each Period ]A set of 4 subtests designed in the form of short games
- CGI-S: Clinical Global Impression-Severity [ Time Frame: Change from Baseline to Week 6 and Week 12 of each Period ]The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
- CGI-I: Clinical Global Impression-Improvement [ Time Frame: Change from Baseline to Week 6 and Week 12 of each Period ]The CGI is a clinician-rated scale utilizing history from the caregiver and incorporating it into a clinical rating, first for severity, and then for clinical follow-up. The CGI-S will be used at the baseline assessment to judge symptom severity as 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; and 7 = Among the most extremely ill. The CGI-I will be used at the Week 8 and End of Treatment/Week 16 visits to judge the change in clinical impression as 1 = Very Much Improved; 2 = Much Improved; 3 = Minimally Improved; 4 = No Change; 5 = Minimally Worse; 6 = Much Worse; and 7 = Very Much Worse.
- VAS: Visual Analog Rating Scale [ Time Frame: Change from Baseline to Week 6 and Week 12 of each Period ]The VAS will be used to measure the severity of three specific behavioral symptoms targeted in this study: behavior problems, language abilities, and eating behavior. For each behavior the caregiver is instructed to mark their impression of the behavior at the baseline visit and again at the Week 8 and End of Treatment/Week 16 visits. The calculated distance in cm between the visit marks thereby demonstrates whether each behavior stayed the same, improved, or worsened during the study and by how much. The scale is from 0 cm (defined as "worst behavior") to 10 cm ("behavior not a problem").
- ABC: Aberrant Behavior Checklist [ Time Frame: Change from Baseline to Week 12 of each Period ]The Aberrant Behavior Checklist (ABC) is a 58-item rating scale used to assess maladaptive behaviors across five original subscales: Irritability (15 items from 0-45), Social Withdrawal (16 items from 0-48), Stereotypy (7 items from 0-21), Hyperactivity (16 items from 0-48), Inappropriate Speech (4 items from 0-12). Additionally, Social Avoidance, a newly developed four-item subscale (from 0-12) of the ABC that captures core social avoidance aspects of Fragile X Syndrome is reported. All items on the ABC are rated from 0 (not at all a problem) to 3 (the problem is severe in degree). Higher scores indicate greater maladaptive behaviors. Differences between Baseline and Week 10 are used as an indicator of change.
- ADAMS: Anxiety, Depression, and Mood Scale [ Time Frame: Change from Baseline to Week 12 of each Period ]The ADAMS (Anxiety, Depression, and Mood Scale) is a 28-item behavior-based informant instrument designed to assess anxiety, depression and mood disorders in individuals with intellectual disability. Items are rated on a scale of 0 ("behavior has not occurred, or is not a problem") to 3 ("behavior occurs a lot, or is a severe problem"). The scale is composed of 5 factors which address: Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety and Obsessive/Compulsive Behavior.
- Vineland-3 Rating Scale [ Time Frame: Change from Baseline to 12 of each Period ]The VABS-III is a caregiver survey interview that measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Adaptive Behavior Composite (ABC) score is calculated from the caregiver responses using age-adjusted scoring tables. ABC scores range from 20 to 160 and indicate low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.
- ERP: Event Related Potentials [ Time Frame: Change from Baseline to Week 12 of each Period ]An EEG (electroencephalogram) maps timing of a subject's responses to sounds heard in a headset.
- Eye Tracking [ Time Frame: Change from Baseline Week 12 of each Period ]Subjects will view pictures shown on the screen. Each assessment begins with presentation of a scrambled face image followed immediately by its matched face image. Measurements include looking time to the eye region of interest (ROI), and number of fixations to the eye ROI, as well as pupil dilatation by pupilometry.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03569631
|Contact: Melissa R Baer, MS, CCRC||312.563.6636||Melissa_R_Baer@rush.edu|
|United States, Illinois|
|Rush University Medical Center||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Melissa R Baer, MS, CCRC 312-563-6636 Melissa_R_Baer@rush.edu|
|Principal Investigator: Elizabeth Berry-Kravis, MD,PhD|