Clinical trial NCT01482143: Clinical Study to Assess the Pharmacokinetics, Safety and Tolerability of Single and Multiple Oral Doses of AFQ056 in Children With Fragile X Syndrome (FXS)
Official title: Sequential, Two-period Study to Assess the Pharmacokinetics, Safety & Tolerability of Single and Multiple Oral Doses of AFQ056 in Patients With FXS (Fragile X Syndrome) Aged 5-11 Years (Cohort 1) and 3-4 Years (Cohort 2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fragile X Syndrome
Keywords: Fragile X Syndrome
pharmacokinetics
safety and tolerability
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-11-30
Enrollment: 21
Sex: ALL
Minimum age (years): 3
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The aim of this study is to characterize the pharmacokinetics and safety/tolerability of AFQ056 in children with Fragile X Syndrome(FXS)


Eligibility criteria: Inclusion Criteria:

* Genetically confirmed diagnosis of FXS
* At Screening and first baseline, vital signs, body weight and body mass index (BMI) must be age-specific within normal ranges.

Exclusion Criteria:

* Use of any other investigational drug within 30 days or 5 half-lives (whichever is longer) of the investigational drug prior to screening until end of study visit.
* History of hypersensitivity to AFQ056 or any mGluR antagonist.
* Female patients who are confirmed or suspected to be sexually active.
* History or presence of any clinically significant disease of any major system organ class, within the past 2 years prior to screening including but not limited to psychiatric, neurological, cardiovascular, endocrine, metabolic, renal, or gastrointestinal disorders (except for typical features of FXS).
* Smokers.
* Loss of ≥10% of total blood volume within 8 weeks (or less if required for this age group and/or by local regulation) prior to dosing or longer if required for this age group and/or by local regulation.
* Significant illness that did not completely resolve at least four weeks prior to the first baseline visit.
* Any abnormal laboratory values at screening or first baseline that are in the opinion of the investigator clinically significant and may jeopardize the safety of the study subject.
* Use of (or use within at least 5 half lives before dosing) concomitant medications that are strong/moderate inhibitors or inducers of CYP1A1/2, CYP2C9/19 or CYP3A4
* History or presence of Hepatitis B/C or HIV at screening

Primary outcomes:
measure: The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume] (AUCinf)
timeFrame: Time Frame: Day 1 (period 1): 0.5, 2, 4, 8, 12, 24 hours post-dose; Day 7 (period 2): pre-dose; 0.5, 2, 4, 8 hours post dose
measure: The area under the plasma (or serum or blood) concentration-time curve from time zero to the time of the last quantifiable concentration [mass x time / volume] (AUClast)
timeFrame: Time Frame: Day 1 (period 1): 0.5, 2, 4, 8, 12, 24 hours post-dose; Day 7 (period 2): pre-dose; 0.5, 2, 4, 8 hours post dose
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Time Frame: Day 1 (period 1): 0.5, 2, 4, 8, 12, 24 hours post-dose; Day 7 (period 2): pre-dose; 0.5, 2, 4, 8 hours post dose
Secondary outcomes:
measure: Physical examination
timeFrame: Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7
measure: Vital signs and body measurements
timeFrame: Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7
measure: Electrocardiograms
timeFrame: Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7
measure: hematology
timeFrame: Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7
measure: blood chemistry
timeFrame: Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7
measure: neurological examination
timeFrame: Screening: once anytime between Day -30 and Day -1; once on Day 7
measure: Adverse events (AE) monitoring
timeFrame: During the study (total of approximately 32 days) and 3 days after study completion
measure: Serious adverse events (SAE) monitoring
timeFrame: During the study (total of approximately 32 days) and 30 days after study completion
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Sant Cugat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: