Efficacy, Safety and Tolerability of AFQ056 in Fragile X Patients

• ClinicalTrials.gov Identifier: NCT00718341
• Recruitment Status: Completed
• First Posted: July 18, 2008
• Last Update Posted: May 6, 2010
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fragile X Syndrome	Drug: AF056; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: June 2008
• Actual Primary Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1	Drug: AF056
Placebo Comparator: 2	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Aberrant-Behavior Checklist- Community Edition

Secondary Outcome Measures :

1. 28 days treatment with AFQ056 on behavior (communication, socialization, daily living, repetitive behaviors, anxiety/avoidance, clinical global improvement)
2. 28 days treatment with AFQ056 on cognition (receptive language, attention, vigilance…)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 35 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

France

Novartis Investigator Site

Bron cedex, France, 69677

Italy

Novartis Investigator Site

Rome, Italy, 00168

Switzerland

Novartis Investigator Site

Lausanne, Switzerland, 1011

Sponsors and Collaborators

Novartis

Investigators

• Principal Investigator: Novartis; Novartis investigator site

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: External Affairs, Novartis
• ClinicalTrials.gov Identifier: NCT00718341 History of Changes
• Other Study ID Numbers: CAFQ056A2204
• First Posted: July 18, 2008
• Last Update Posted: May 6, 2010
• Last Verified: May 2010

Keywords provided by Novartis:

Fragile X Syndrome, adults, efficacy

Additional relevant MeSH terms:

Fragile X Syndrome; Syndrome; Disease; Pathologic Processes; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System