A Safety Study of NNZ-2566 in Patients With Fragile X Syndrome
The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of Fragile X Syndrome in adolescent and adult males.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study of NNZ-2566 in Fragile X Syndrome|
- Adverse events [ Time Frame: Through to Day 56 ] [ Designated as safety issue: Yes ]Incidence of adverse events (AE), including Serious adverse events (SAE), will be evaluated between the two NNZ-2566 doses and placebo. Incidence of AEs from randomized dosing through to Day 56 post randomization. Incidence of SAEs from randomization through to Day 56 post randomization.
- Physiological changes [ Time Frame: Baseline through to Day 56 ] [ Designated as safety issue: No ]Serum levels and changes of standard hematology, and chemistry parameters (including thyroid function) will be calculated from Baseline through to Day 56. Fundoscopy and tonsil size will be documented at Baseline, and Days 14, 28, 42 and 56. Flow cytometry will be used to assess the phosphorylation status of the enzymes Akt and extracellular signal-regulated kinase (ERK) in peripheral lymphocytes, on blood samples obtained on Days 14, 28, 42 and 56. Electrocardiogram (ECG) will be assessed at Screening, Days 14, 21, 28, 35, 42 and 56.
- Behavior [ Time Frame: Baseline through to Day 56 ] [ Designated as safety issue: No ]Symptom severity according to the Fragile X Symptom Rating Scale, Clinician Domain Specific Top Three Concerns-VAS, Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scale (VABS), Child and Adolescent Symptom Inventory-Anxiety Scale (CASI-16), Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS-PDD), Expressive Language Sampling and Clinical Global Impression of Severity (CGI-S).
- Global and Functional outcome Measures [ Time Frame: Baseline through to Day 56 ] [ Designated as safety issue: No ]
Global outcome as measured by the change in scores in the Clinical Global Impression - Severity and Improvement scales (CGI-S and -I) and the KiTap measure of cognition from baseline, during treatment, and post treatment.
Global and Functional outcome as measured by changes in scores in the Fragile X Symptom Rating Scale, Clinician Domain Specific Top Three Concerns-VAS, Caregiver Top Three Concerns (related to the subject's Fragile X syndrome) as assessed via a Visual Analogue Scale (VAS), CASI-20, CYBOCS-PDD, Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scales (VABS) and Expressive Language Sampling will be assessed during treatment.
- Pharmacokinetics [ Time Frame: During treatment ] [ Designated as safety issue: No ]The following pharmacokinetic measures will be calculated from NNZ-2566 concentrations in whole blood: Cmax (Peak), Cmin (trough), C0-6 at steady state, and area under the curve (AUC).
- Computerized eye-tracking [ Time Frame: During treatment ] [ Designated as safety issue: No ]Computer-based eye tracking assessments will be done on Days 14, 28 and 42.
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (2g in 50 milliliter vials) for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.
Other Name: NNZ-2566
Placebo Comparator: Placebo (strawberry flavored solution)
Strawberry flavored solution and Water
Strawberry flavored solution
Other Name: Strawberry flavored solution 0.5% v/v in Water for Injection
Fragile X Syndrome is a genetically determined neurological disorder in which affected individuals are intellectually handicapped to varying degrees and display a variety of associated psychiatric symptoms. Clinically, Fragile X Syndrome is characterized by intellectual handicap, hyperactivity and attentional problems, autism spectrum symptoms, emotional lability and epilepsy. The epilepsy seen in Fragile X Syndrome is most commonly present in childhood, but then gradually remits towards adulthood. Physical features such as prominent ears and jaw, and hyper-extensibility of joints are frequently present but are not diagnostic. Intellectual handicap is the most common feature defining the phenotype. Treatment for the disorder is symptomatic - focusing on the management of symptoms - and supportive, requiring a multidisciplinary approach.
This study will investigate the safety and tolerability of treatment with oral administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescent or adult males with Fragile X Syndrome. The study also will also investigate measures of efficacy during treatment.
|Contact: Joseph Horrigan, MDemail@example.com|
|Contact: Nancy Jones, PhDfirstname.lastname@example.org|
|United States, Colorado|
|Children's Hospital Colorado||Not yet recruiting|
|Denver, Colorado, United States, 80045|
|Contact: Nanastasia Welnick 720-777-8608 Nanastasia.Welnick@childrenscolorado.org|
|Principal Investigator: Nicole Tartaglia, MD|
|United States, Georgia|
|Emory University||Not yet recruiting|
|Atlanta, Georgia, United States, 30033|
|Contact: Krista Charen 404-778-8479 email@example.com|
|Principal Investigator: Jeannie Visootsak, MD|
|United States, Illinois|
|Rush University Medical Center||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Rebecca Levin 312-563-6640 Rebecca_Levin@rush.edu|
|Contact: Jamie A Chin (312) 942-0025 Jamie_A_Chin@rush.edu|
|Principal Investigator: Elizabeth M Berry-Kravis, MD|
|United States, Massachusetts|
|University of Massachusetts Medical School||Not yet recruiting|
|Worcester, Massachusetts, United States, 01655|
|Contact: Kara Manchester 774-455-4115 firstname.lastname@example.org|
|Principal Investigator: Jean Frazier, MD|
|United States, New York|
|Mount Sinai School of Medicine||Not yet recruiting|
|New York, New York, United States, 10029|
|Contact: Stacey Lurie 212-241-3692 email@example.com|
|Principal Investigator: Alexander Kolevzon, MD|
|United States, Pennsylvania|
|Suburban Research Associates||Recruiting|
|Media, Pennsylvania, United States, 19063|
|Contact: Nathan Blubaugh 610-891-9024 ext 103 firstname.lastname@example.org|
|Contact: Nikki Thomas 610-891-7200 Nthomas@suburbanresearch.com|
|Principal Investigator: Shivkumar Hatti, MD|
|Principal Investigator:||Elizabeth M Berry-Kravis, MD||Rush University Medical Center|
|Principal Investigator:||Jeannie Visootsak, MD||Emory University|
|Principal Investigator:||Alexander Kolevzon, MD||Mount Sinai School of Medicine|
|Principal Investigator:||Nicole Tartaglia, MD||Children's Hospital Colorado|
|Principal Investigator:||Jean Frazier, MD||University of Massachusetts, Worcester|
|Principal Investigator:||Shivkumar Hatti, MD||Suburban Research Associates|