Clinical trial NCT00718341: Efficacy, Safety and Tolerability of AFQ056 in Fragile X Patients
Official title: A Multi-centre, Randomized, Double-blind, Placebo Controlled, Two-period, Crossover Proof-of-concept Study in Male Patients With Fragile X Syndrome to Assess the Efficacy, Safety and Tolerability of Multiple Oral Doses of AFQ056
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fragile X Syndrome
Keywords: Fragile X Syndrome, adults, efficacy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-07-18
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability and efficacy of multiple doses of AFQ056 in patients with Fragile X Syndrome. The dose range will be 50 to 150 mg b.i.d. The primary read-out of efficacy is reduction in Aberrant-Behavior Checklist score.


Eligibility criteria: Inclusion Criteria:

* Male, non-smoking patients between 18 and 35 years of age (both inclusive).
* Patients with fmr1 full mutation (\> 200 CGG repeats)
* Patients with a Clinical Global Impression Severity Score (CGI-S) of \> 4 (moderately ill)
* Patients with a score of \>20 in the ABC-C scale (at screening)
* Patients with a mental age of ≥ 48 months as measured by the Stanford-Binet test

Exclusion Criteria:

* Patients with DSM-IV diagnosis of schizophrenia, history and/or presence of psychosis, confusional states and/or repeated hallucinations.
* Patients with a history of seizures in the past 5 years without any therapeutic treatment controlling the disorders.
* Patients under stable anti-convulsant therapies that experienced seizures in the 2 years prior to randomization
* Patients with ECG abnormalities, autonomic dysfunctions, bronchospastic diseases, drug or atopic allergy
* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs
* Patients using (or have used within four weeks before randomization) concomitant medications that are potent inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, etc.)

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Aberrant-Behavior Checklist- Community Edition
Secondary outcomes:
measure: 28 days treatment with AFQ056 on behavior (communication, socialization, daily living, repetitive behaviors, anxiety/avoidance, clinical global improvement)
measure: 28 days treatment with AFQ056 on cognition (receptive language, attention, vigilance…)
Other outcomes:
Locations:
city: Bron cedex
country: France
facility: Novartis Investigator Site
city: Rome
country: Italy
facility: Novartis Investigator Site
city: Lausanne
country: Switzerland
facility: Novartis Investigator Site
Study officials:
affiliation: Novartis investigator site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, Ramos FJ, Cornish K, He Y, Paulding C, Neri G, Chen F, Hadjikhani N, Martinet D, Meyer J, Beckmann JS, Delange K, Brun A, Bussy G, Gasparini F, Hilse T, Floesser A, Branson J, Bilbe G, Johns D, Gomez-Mancilla B. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med. 2011 Jan 5;3(64):64ra1. doi: 10.1126/scitranslmed.3001708.