Clinical Study to Assess the Pharmacokinetics, Safety and Tolerability of Single and Multiple Oral Doses of AFQ056 in Children With Fragile X Syndrome (FXS)

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

Official Title
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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)

Conditions
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Fragile X Syndrome

Intervention / Treatment
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* Drug: AFQ056


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Study subjects<br> | Drug: AFQ056<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume] (AUCinf) |  | 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 | 
| 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) |  | 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 | 
| Maximum observed plasma concentration (Cmax) |  | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical examination |  | Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7 | 
| Vital signs and body measurements |  | Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7 | 
| Electrocardiograms |  | Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7 | 
| hematology |  | Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7 | 
| blood chemistry |  | Screening: once anytime between Day -30 and Day -1; once anytime between 24-72 hours after Day 7 | 
| neurological examination |  | Screening: once anytime between Day -30 and Day -1; once on Day 7 | 
| Adverse events (AE) monitoring |  | During the study (total of approximately 32 days) and 3 days after study completion | 
| Serious adverse events (SAE) monitoring |  | During the study (total of approximately 32 days) and 30 days after study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fragile X Syndrome, pharmacokinetics, safety and tolerability