Clinical Trials Register

Summary
EudraCT Number:	2007-005088-82
Sponsor's Protocol Code Number:	CAFQ056A2204
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-04-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2007-005088-82

A.3

Full title of the trial

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

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CAFQ056A2204

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	NOVARTIS FARMA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	AFQ056
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	543906-09-8
D.3.9.2	Current sponsor code	AFQ056
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	AFQ056
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	543906-09-8
D.3.9.2	Current sponsor code	AFQ056
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Fragile X Syndrome

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10017324
E.1.2	Term	Fragile X syndrome

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of multiple oral doses of AFQ056 in reducing the global score of the Aberrant Behavior Checklist - Community Edition (ABC-C) in FZS patients. To assess the safety and tolerability of nultiple titrated oral doses of AFQ056 in FXS patients

E.2.2

Secondary objectives of the trial

-To assess the efficacy of multiple oral doses of AFQ056 in reducing social withdrawal in Fragile X patients by using the Repetitive Behavior Scale (RBS), the Vineland Adaptive Behavior Scale (VABS) and the Social Responsiveness Scale (SRS). -To assess the efficacy of multiple oral doses of AFQ056 on the global improvement of symptoms in Fragile X patients by using the Clinical Global Impression Scale (CGI) and the Visual Analogue Scale (VAS), which rates the changes in one target behavior chosen by the caregiver. -To assess the efficacy of multiple doses on AFQ056 in reducing cognitive deficits in Fragile X patients by using the Computerized CANTAB test battery.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male, non-smoking patients between 18 and 35 years of age (both inclusive). 2. Patients with confirmed diagnosis of Fragile X based upon genetic testing results (full mutation > 200 CGG repeats), a Clinical Global Impression Severity Score (CGI-S) of > 4 (moderately ill), a score of >20 in the ABC-C scale (performed at screening) and a mental age of ≥ 48 months as measured by the Standford-Binet test. 3. Patients treated with psychotropic treatment and/or anticonvulsant therapy are allowed to enter the study provided that they are on a stable regimen for at least 4 weeks prior to randomization. 4. Patients must be using a double-barrier local contraception for the entire duration of the study (from screening up to the study completion visit), and refrain from fathering a child in the 3 months following last study drug administration. 5. Patients whose legal guardian has signed an Informed Consent (for the exploratory substudy, an additional separate Informed Consent has to be signed).

E.4

Principal exclusion criteria

1. Patients with DSM-IV diagnosis of schizophrenia. 2. Patients with a history and/or presence of psychosis, confusional states and/or repeated hallucinations. 3. Patients with a history of seizures in the past 5 years without any therapeutic treatment controlling the disorders. 4. Donation or loss of 400 ml or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation. 5. Significant illness within two weeks prior to dosing. 6. A past medical history of clinically significant ECG abnormalities or a family history (grandparents, parents and siblings) of a prolonged QT-interval syndrome. 7. History of autonomic dysfunction (e.g. history of fainting, orthostatic hypotension, sinus arrhythmia). 8. History of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated) 9. History of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). 10. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the patient in case of participation in the study. The investigator should be guided by evidence of any of the following: history of ulcers, gastrointestinal or rectal bleeding; This document (090095a880ef01bb in docbase CREDI_BS) has been digitally signed with external signatures using Entrust PKI. Signatures manifested as of 10/1/2007 9:29:16 AM, signing status at this time: Completed (1 of 1 signatures) Approved for report publication by Magnone Maria-Chiara in Basel at Mon, 01 Oct 2007 09:28:11 CEST Novartis Confidential Page 43 Protocol AFQ056A2204 (Version 01) AFQ056 history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; history or clinical evidence of pancreatic injury or pancreatitis; clinical evidence of liver disease or liver injury as indicated by clinically relevant abnormal liver function tests such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin. If the total bilirubin concentration is increased above 1.5 times the upper normal limit total bilirubin should be differentiated into the direct and indirect reacting bilirubin and the Investigator will make his judgment on the clinical relevance of these data. history or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN values or abnormal urinary constituents (e.g., albuminuria); evidence of urinary obstruction or difficulty in voiding at screening; 11. Patients using (or have used within four weeks before randomization) concomitant medications that are potent inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, etc.) 12. Patients who in the opinion of the investigator, are unsuitable in any other way to participate in this study including being unable to comply with the requirements of the study or displaying abnormalities in safety assessments at baseline .

E.5 End points

E.5.1

Primary end point(s)

To assess the efficacy of multiple oral doses of AFQ056 in reducing the global score of the Aberrant Behavior Checklist – Community Edition (ABC-C) in FXS patients. To assess the safety and tolerability of multiple titrated oral doses of AFQ056 in FXS patients.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

- same IMP used at different dosage

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

category of incapacitated adultsEuropean Clinical Trials Directive EC2001/20)

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2008-06-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-03-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-02-19

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