A Safety Study of NNZ-2566 in Patients With Fragile X Syndrome
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|ClinicalTrials.gov Identifier: NCT01894958|
Recruitment Status : Completed
First Posted : July 10, 2013
Last Update Posted : February 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Fragile X Syndrome||Drug: NNZ-2566 Drug: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||72 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study of NNZ-2566 in Fragile X Syndrome|
|Study Start Date :||January 2014|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||October 2015|
Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (2g in 50mL vials or 3g in 30mL bottles) for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.
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
- Adverse events [ Time Frame: Through to Day 56 ]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 ]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 ]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 ]
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 ]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: Baseline through to Day 56 ]Computer-based eye tracking assessments will be done on Days 14, 28 and 42.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01894958
|Principal Investigator:||Elizabeth M Berry-Kravis, MD||Rush University Medical Center|
|Principal Investigator:||Joseph Cubells, MD, PhD||Emory University|
|Principal Investigator:||Alexander Kolevzon, MD||Icahn School of Medicine at Mount Sinai|
|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|
|Principal Investigator:||Craig Erickson, MD||Children's Hospital Medical Center, Cincinnati|
|Principal Investigator:||Thomas Challman, MD||Autism & Developmental Medicine Institute Geisinger Health System|
|Principal Investigator:||Kevin Sanders, MD||Vanderbilt University Medical Center|
|Principal Investigator:||Diane Treadwell-Deering, MD||Baylor College of Medicine|
|Principal Investigator:||Jeffrey Innis, MD||University of Michigan|
|Principal Investigator:||Howard Needleman, MD||University of Nebraska|
|Principal Investigator:||Steve Skinner, MD||Greenwood Genetic Center|
|Principal Investigator:||Bryan King, MD||Seattle Children's Hospital|
|Principal Investigator:||Randi Hagerman, MD||UC Davis MIND Institute|
|Principal Investigator:||Robert Findling, MD||Hugo W. Moser Research Institute at Kennedy Krieger, Inc.|