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

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)

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

Study Overview

• Status: Completed
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: AFQ056

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Catalunya
    • Sant Cugat, Catalunya, Spain, 08190
      • Novartis Investigative Site
• United States
  • California
    • Sacramento, California, United States, 95817
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Novartis Investigative Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232-7548
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All Study subjects	Drug: AFQ056

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CAFQ056B2154 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: November 21, 2011
• First Submitted That Met QC Criteria: November 29, 2011
• First Posted (Estimate): November 30, 2011

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: pharmacokinetics; Fragile X Syndrome; safety and tolerability
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome
• Other Study ID Numbers: CAFQ056B2154; 2011-004867-65 (EudraCT Number)