Clinical Trials Register

Summary
EudraCT Number:	2006-005585-40
Sponsor's Protocol Code Number:	A7501021
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2007-01-29
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2006-005585-40

A.3

Full title of the trial

A randomized, parallel group, multiple dose, 6 week study to evaluate safety, tolerability, and pharmacokinetics of asenapine in elderly subjects with psychosis.

A.3.2

Name or abbreviated title of the trial where available

N/A

A.4.1

Sponsor's protocol code number

A7501021

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

N/A

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	NV Organon
B.1.3.4	Country	Netherlands
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	Asenapine
D.3.2	Product code	Org 5222
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Sublingual use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	asenapine
D.3.9.1	CAS number	85650-56-2
D.3.9.2	Current sponsor code	Org 5222
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	2
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	Asenapine
D.3.2	Product code	Org 5222
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Sublingual use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	asenapine
D.3.9.1	CAS number	85650-56-2
D.3.9.2	Current sponsor code	Org 5222
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	5
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: 3
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	Asenapine
D.3.2	Product code	Org 5222
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Sublingual use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	asenapine
D.3.9.1	CAS number	85650-56-2
D.3.9.3	Other descriptive name	Org 5222
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.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute and maintenance treatment of schizophrenia and manic episodes associated with bipolar I disorder.

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	LLT
E.1.2	Classification code	10039626
E.1.2	Term	Schizophrenia

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To evaluate the safety and tolerability 6-weeks of asenapine up to doses of 10 mg BID in elderly subjects with psychosis.
• To evaluate the pharmacokinetics of multiple dose administration of asenapine up to doses of 10 mg BID in elderly subjects with psychosis.

E.2.2

Secondary objectives of the trial

• To explore the pharmacokinetic/pharmacodynamic relationship of asenapine in elderly subjects with psychosis.
• To characterize tolerability of the 2 titration schedules.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

General Inclusion Criteria:
Subjects should:

1. be male or female subjects, 65 years of age or greater.

2. willing to sign written informed consent (subjects unable or incapable of signing may participate if the legally authorized representative provides consent and the subject affirms their participation).

3. be fluent in the language of the investigator, and study staff (including raters) and informed consent

4. have a caregiver or an identified responsible person (eg, family member, social worker, caseworker or nurse) considered reliable by the investigator in providing support to the subject to ensure compliance with study treatment, outpatient visits, and protocol procedures.

Diagnoses
Subjects should:

1. have psychotic symptoms as evidenced by a score of 4 or more on at least 1 of the following PANSS items:

P1 Delusions
P3 Hallucinatory behavior
P4 Excitement
P7 Hostility
G14 Poor Impulse Control

2. have a minimum PANSS total score >50 at screening.

3. have a Clinical Global Impression – Severity of Illness (CGI S) scale score of at least 3 at screening.
Pre-trial medication
Subjects should:

1. have responded positively to an antipsychotic medication other than clozapine (Clozaril®).

2. have discontinued depot neuroleptics prior to first dose (Day 1) (last dose of depot neuroleptics should be received more than 1 dosing interval minus 1 week prior to first dose).

E.4

Principal exclusion criteria

Subjects should be excluded from the trial if they:

Psychiatric Exclusion Criteria

1. have current (within 6 months prior to screening) DSM IV TR™ defined substance abuse/dependence (excluding nicotine and caffeine).

2. have an established diagnosis of delirium according to DSM IV TR™ criteria.

3. are at imminent risk of self-harm or are at risk of harming to others.

4. have a score of 2 on any of items 7,10, or 11 on the Modified InterSePT scale for suicidal thinking (ISST).

5. have a score of 17 or below on Mini Mental State Examination (MMSE).

Medical Exclusion Criteria

1. have an uncontrolled, unstable clinically significant medical condition (eg, renal, hepatic, endocrine, respiratory, cardiovascular, metabolic, hematologic, immunologic, cerebrovascular disease, anorexia or obesity [body mass index (BMI) ≤ 18.5 or >35] or malignancy), which, in the opinion of the investigator, may interfere with the interpretation of safety, efficacy, or pharmacokinetic evaluations. In case of BMI beyond the limits mentioned above, discussion should occur between the investigator and the sponsor before enrolling such subject(s) in the study.

2. have jaundice or total bilirubin of >2X upper limit of normal (ULN).

3. have any clinically significant abnormal laboratory, vital signs, physical examination, or electrocardiogram (ECG) findings at screening and any significant changes at randomization that, in the opinion of the investigator, precludes trial participation.

4. have narrow angle glaucoma.

5. have a seizure disorder beyond childhood or are taking any anticonvulsants to prevent seizures.

6. have known serological evidence of HIV antibody.

7. have a history of neuromalignant syndrome in the past 5 years.

8. have a life-time history of cerebrovascular accident (e.g., documented history of stroke or TIA’s).

9. have a history of myocardial infarction in past 5 years.

10. have Parkinson’s disease.

Medications

1. have been judged by the principal investigator to be medically noncompliant in the management of their disease.

2. have been judged by the principal investigator to be unable to reduce his or her daily benzodiazepine intake during inpatient phase to a maximum of 6 mg/day of lorazepam (or the equivalent dose of another short-acting benzodiazepine).

3. have been treated with clozapine in the previous 6 months;
4. have previously participated in an asenapine clinical trial.
5. have taken an investigational drug within 30 days prior to first dose (Day 1).

E.5 End points

E.5.1

Primary end point(s)

There are not primary endpoints per se as there would be in an efficacy study. This is purely a safety study. Detailed methodology for summary and statistical analysis will be found in the Statistical Analysis Plan.
Sample Size Determination
120 subjects with a 20% drop out rate will likely yield exposure data on 100 elderly subjects
Pharmacokinetic/pharmacodynamic modeling analysis
- The relationship between asenapine exposure and PANSS and CGI-S scores will be investigated
- Pharmacokinetic parameters such as Cmax, tmax, and AUC will be estimated from plasma concentration-time data
- Descriptive statistics will be used to analyze concomitant medications, adverse events, changes in ESRS-A, lab values, and vital signs parameters

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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

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

Yes

E.8.1.7.1

Other trial design description

Open label will be applicable from treatment day 5

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Asenapine in 2 different titration schedules

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

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

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

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

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

Willing to sign written informed consent (subjects unable or incapable of signing may participate if the legally authorized representative provides consent and the subject affirms their participation)

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

120

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)

There are 2 follow-up visits that occur after dosing has stopped: one at 7 days to list conmeds and Adverse Events and one at 30 days to elicit any Severe Adverse Events that may have occurred. Subjects return to their pre-protocol care situation.

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

2007-03-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-03-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2008-12-20

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials