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: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase IIa Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study of NNZ-2566 in Fragile X Syndrome|
- Adverse events [ Time Frame: Through to Day 84 ] [ 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 dosing through to Day 84 post randomization. Incidence of SAEs from randomization through to Day 84 post randomization.
- Physiological changes [ Time Frame: Baseline through to Day 70 ] [ 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 70. Fundoscopy and tonsil size will be documented at Baseline, and Days 14, 28, 42, 56 and 70. 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, 56, and 70. Electrocardiogram (ECG) will be assessed at Screening, Baseline, Days 28, 42, 56 and 70.
- Behavior [ Time Frame: Baseline through to Day 70 ] [ 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 70 ] [ 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 score in the Fragile X Symptom Rating Scale, Clinician Domain Specific Top Three Concerns-VAS, the caregiver assessment of the top three causes for concern (related to the subject's Fragile X syndrome) as assessed via a Visual Analogue Scale (VAS), CASI-16, CYBOCS-PDD, Aberrant Behavior Checklist (ABC), Vineland Adaptive Behavior Scales (VABS) and Expressive Language Sampling will be assessed from baseline and during treatment.
- Pharmacokinetics [ Time Frame: Baseline through to Day 70 ] [ Designated as safety issue: No ]The following pharmacokinetic measures will be calculated from NNZ-2566 concentrations in whole blood: Cmax (Peak), Cmin (trough) C0-4 at steady state, and area under the curve (AUC).
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||October 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 for Injection
Strawberry flavored solution and Water for Injection
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, MDfirstname.lastname@example.org|
|Contact: Nancy Jones, PhDemail@example.com|
|United States, Illinois|
|Rush University Medical Center||Not yet recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Elizabeth M Berry-Kravis, MD Elizabeth_Berry-Kravis@rush.edu|
|Principal Investigator:||Elizabeth M Berry-Kravis, MD||Rush University Medical Center|