Clinical Trials Register

Summary
EudraCT Number:	2010-020470-42
Sponsor's Protocol Code Number:	WN25308
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-11-30
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

2010-020470-42

A.3

Full title of the trial

A Phase III, multi-center, randomized, 24 week, double-blind, parallel-group, placebocontrolled study to evaluate efficacy and safety of RO4917838 in stable patients with persistent, predominant negative symptoms of schizophrenia treated with antipsychotics followed by a 28 week, double-blind treatment period.

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

WN25308

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	F. Hoffmann - La Roche Ltd.
B.1.3.4	Country	Switzerland
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.3.1	Product name	GlyT1(1)
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.8	INN - Proposed INN	non ancora disponibile
D.3.9.1	CAS number	845614-11-1
D.3.9.2	Current sponsor code	RO4917838/F18
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	10
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.3.1	Product name	GlyT1(1)
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.8	INN - Proposed INN	non ancora disponibile
D.3.9.1	CAS number	845614-11-1
D.3.9.2	Current sponsor code	RO4917838/F18
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	20
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	Film-coated tablet
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	Film-coated tablet
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

Treatment of negative symptoms for patients with schizophrenia treated with antipsychotics.

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	10039626

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• Evaluate efficacy of 24 weeks treatment with RO4917838 in the PANSS negative symptom factor score in patients with persistent, predominant negative symptoms of schizophrenia treated with antipsychotics; • Evaluate safety and tolerability of 24 weeks treatment with RO4917838 in patients with persistent, predominant negative symptoms of schizophrenia treated with antipsychotics.

E.2.2

Secondary objectives of the trial

• To evaluate efficacy of 24 weeks treatment with RO4917838 in personal and social functioning using PSP total score in patients with persistent, predominant negative symptoms of schizophrenia treated with antipsychotics.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A patient may be included into Prospective Stabilization Period if the answer to all of the following statements is “yes”: Demographic 1. Male and female patients, aged 18 and above. 2. Female patients who are not either surgically sterile (e.g., tubal ligation or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year confirmed by a negative hormone panel) must agree for the entire study duration to use one of the following forms of contraception: (1) systemic hormonal treatment (2) an IUD which was implanted at least 2 months prior to screening or (3) ``doublebarrier`` contraception (condom, diaphragm and spermicide are each considered a barrier), or (4) agree to remain sexually abstinent during the entire study period (when contraception is not acceptable for cultural or religious beliefs). Procedural 3. Sign written informed consent after the scope and nature of the investigation have been explained to them before screening evaluations and willing to comply with the study restrictions. 4. Are fluent in the language of the investigator, study staff (including raters), and the informed consent. 5. Have a caregiver (e.g., family member, social worker, caseworker, or nurse that spends > 4 hours/week with the patient) considered reliable by the investigator in providing support to the patient to ensure compliance with study treatment, assessment visits, and protocol procedures; and, who will be able to provide input helpful for completing study rating scales, i.e. PANSS and PSP. The caregiver needs to be able and willing to attend study/clinic visits with the patients or to provide input via the phone. The caregiver must provide written consent to participate in this study. Neuropsychiatric 6. Based on the screening SCID-CT, a DSM-IV- TR diagnosis of schizophrenia, paranoid (295.30), disorganized (295.10), residual (295.60), undifferentiated (295.90) or catatonic subtype (295.20). 7. A score of 40 or greater on the sum of the 14 PANSS negative and disorganized thought factor items (items scored 1-7 for a maximum possible score of 98). Et al..

E.4

Principal exclusion criteria

A patient will be excluded from Prospective Stabilization Period if the answer to any of the following statements is “yes”. Medical Status 1. The patient has evidence of clinically significant, uncontrolled or unstable cardiovascular, renal, hepatic (incl. AST or ALT at or above 3x ULN, or bilirubin at or above 2x ULN), gastrointestinal, hematologic, immunological, neurological, endocrine, metabolic or pulmonary disease, anorexia [body mass index (BMI) < 18.5] or obesity [BMI > 40] (as determined by medical history, clinical laboratory or ECG results, or physical examination) that would increase the risk associated with taking study medication or would confound the interpretation of the study results. 2. Hemoglobin less than 130 g/L (13 g/dL) in males or less than 120 g/L (12 g/dL) in females. 3. The patient has history of hemolytic anemia including hemoglobinopathies (e.g., thalassemia major, sickle-cell anemia), RBC membrane diseases (e.g., hereditary sphreocytosis), and G6PDH (glucose-6-phosphate dehydrogenase) deficiency or anemia of any cause. 4. Any clinically significant abnormal laboratory data, vital signs, physical examination at screening or baseline which in the opinion of the investigator, would interfere with safety assessments. 5. Clinically significant electrocardiogram (ECG) abnormality at screening, including sinus bradycardia (resting heart rate < 50 beats per minute), atrial fibrillation, 2nd or 3rd degree atrioventricular block, prolonged QTc (QTcF ≥ 450 ms in males and ≥ 470 ms in females) history of congenital long QT syndromes, or risk of Torsades de Pointes because of family history of sudden death, etc. 6. Positive result on the serum pregnancy test or are breast feeding at screening, or intend to become pregnant during the course of the trial. 7. History of neuroleptic malignant syndrome (NMS). Neuropsychiatric 8. Depressive symptoms, defined as a score of 9 or greater on the Calgary Depression Rating Scale for Schizophrenia (CDSS). 9. A score of 3 or greater on the global Parkinsonism item of the ESRS-A. 10. Based on the DSM-IV-TR criteria and screening SCID-CT have: o other current DSM-IV-TR Axis I diagnosis, such as but not limited to Major Depression, Bipolar, Obsessive Compulsive or Schizoaffective Disorders; o alcohol or substance dependence within 12 months or abuse within 3 months with the exception of nicotine;o dementia, delirium and other amnestic disorder per DSMIV- TR. 11. Diagnosis of mental retardation or severe organic brain syndromes. 12. In the investigator’s judgment, a significant risk of suicide or violent behavior. 13. A prior or current general medical condition that may be impairing cognition or other neuropsychiatric functioning (documented head trauma with a loss of consciousness > 1 hour or clear cognitive or behavioral sequelae, seizure disorder, stroke, neurodegenerative diseases, etc.). 14. Treated with electroconvulsive therapy (ECT) within the 5 months prior to the Prospective Stabilization Period. Et al..

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy: • Mean change from baseline in the PANSS negative symptom factor score at week 24.

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

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

tollerabilita`, qualita` della vita e biomarcatori.

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.6

Cross over

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

Last patient to complete last visit four weeks after the last dose.

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

E.8.9.2

In all countries concerned by the trial days

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)

Yes

F.2 Gender

F.2.1

Female

Yes

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

Yes

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

i pazienti devono avere un caregiver come da criteri di inclusione.

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

170

F.4.2.2

In the whole clinical trial

633

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Ai pazienti che completano il periodo di trattamento di 56 settimane sara` offerta la possibilita` di ricevere il trattamento attivo RO4917838 nella fase di estensione a lungo termine.

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

2010-11-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-11-04

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-04-14

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