Clinical Trials Register

Summary
EudraCT Number:	2012-003445-15
Sponsor's Protocol Code Number:	ALK9072-003
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-11-01
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

Bulgarian Drug Agency

A.2

EudraCT number

2012-003445-15

A.3

Full title of the trial

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of ALKS 9072 in Subjects with Acute Exacerbation of Schizophrenia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to assess how safe and efficient ALKS 9072 is for the treatment of acute exacerbation of schizophrenia

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

ALK9072-003

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01469039

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Alkermes, Inc.
B.1.3.4	Country	United States
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	Alkermes, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Alkermes, Inc
B.5.2	Functional name of contact point	Clinical Developement
B.5.3	Address:
B.5.3.1	Street Address	852 Winter Street
B.5.3.2	Town/ city	Waltham
B.5.3.3	Post code	MA 02451
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 781-609 6542
B.5.5	Fax number	+1 781-609 6542
B.5.6	E-mail	Lisa.Corey@alkermes.com

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	NA
D.3.2	Product code	ALKS 9072
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	aripiprazole lauroxil
D.3.9.1	CAS number	1259305-29-7
D.3.9.2	Current sponsor code	ALKS 9072
D.3.9.3	Other descriptive name	USAN: Aripiprazole Lauroxil; RDC-3317
D.3.9.4	EV Substance Code	SUB05564MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	265
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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	aripiprazole
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
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	ARIPIPRAZOLE
D.3.9.1	CAS number	129722-12-9
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	over-encapsulated aripiprazole
D.3.9.4	EV Substance Code	SUB05564MIG
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	15
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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	Emulsion for injection
D.8.4	Route of administration of the placebo	Intramuscular 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
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

acute exacerbation of schizophrenia

E.1.1.1

Medical condition in easily understood language

mental disease called schizophrenia

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10001064
E.1.2	Term	Acute schizophrenia
E.1.2	System Organ Class	100000004873

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10046152
E.1.2	Term	Unspecified schizophrenia, chronic state with acute exacerbation
E.1.2	System Organ Class	100000004873

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10039630
E.1.2	Term	Schizophrenia exacerbated
E.1.2	System Organ Class	100000004873

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 determine the efficacy of ALKS 9072 for the treatment of schizophrenia in subjects experiencing an acute exacerbation

E.2.2

Secondary objectives of the trial

To determine the safety and tolerability of ALKS 9072

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Genotype Sampling: If a subject consents, a second sample will be collected and stored for future use to explore potential genetic associations with efficacy, adverse effects, symptoms or outcomes.

E.3

Principal inclusion criteria

1.Willing and able to provide informed consent; subject has signed the informed consent form before initiation of any study specific procedures
2.Male or female age 18 to 70 years
3.Diagnosis of schizophrenia according to DSM-IV-TR criteria
-Currently experiencing an acute exacerbation or relapse with onset of less than 2 months prior to screening
-If inpatient at screening, has been hospitalized for less than 2 weeks for the current exacerbation
- ≥ 2 years have elapsed since initial onset of active-phase schizophrenia symptoms
4.Has previously had a clinically significant beneficial response (improvement in schizophrenia symptoms), as determined by the investigator, to treatment with an antipsychotic medication other than clozapine
5.Has been able to achieve outpatient status for more than 3 months in the past year
6.PANSS that meets the following criteria at screening and baseline:
•Total score between 70 and 120, inclusive
•Score of ≥ 4 (moderate or greater) for ≥ 2 of the following Positive Scale (P) items:
o Item 1 (P1; delusions)
o Item 2 (P2; conceptual disorganization)
o Item 3 (P3; hallucinatory behavior)
o Item 6 (P6; suspiciousness/persecution)
7.GI-S score ≥ 4 at screening and baseline
8.BMI of 18.5 to 40.0 kg/m2 (inclusive)
9.Resides in a stable living situation, in the opinion of the investigator
10.Has an identified reliable informant, in the opinion of the investigator
11. Meets contraceptive requirements defined in the protocol
12. Fluent (oral and written) in the language in which standardized tests will be administered, and can be reliably rated
13. Willing and able to be confined to an inpatient study unit for 2 weeks (or longer if clinically indicated)

E.4

Principal exclusion criteria

1. History of poor or inadequate clinical response to treatment with aripiprazole
2. History of treatment resistance, defined as failure to respond to 2 adequate trials of different antipsychotic medications (a minimum of 4 weeks at the subject's maximum tolerated dose)
3. Known or suspected intolerance of, allergy, or hypersensitivity to aripiprazole, its excipients, other antipsychotic agent, or INTRALIPID® (including peanuts, soy, egg, or glycerol)
4.History of neuroleptic malignant syndrome, clinically significant tardive dyskinesia, tardive dystonia, or other medical condition that would convey undue risk or interfere with study assessments. Clinically significant extrapyramidal symptoms at screening or baseline
5.Answer “Yes” on items 4 or 5 of the C-SSRS (ideation) with the most recent episode occurring within the past 2 months, or answer “Yes” to any of the 5 items (behavior) with an episode occurring within the last year
6.Diagnosis (according to DSM-IV-TR criteria) of substance (including alcohol) dependence currently or within 6 months before screening or abuse within 3 months before screening (exception: nicotine and caffeine are allowable)
7.Comorbid neuropsychiatric disorders including;
• Life time diagnosis of schizoaffective disorder or bipolar disorder, or current, untreated or unstable major depressive disorder.
• Clinically significant cognitive difficulties including dementia, delirium, or amnestic syndromes that have been present within the past 2 years and would interfere with participation in the study.
• Any other psychiatric condition that would, in the judgment of the investigator, interfere with participation in the study.
8. Clinically significant or unstable medical illness/condition/disorder that would be anticipated, in the investigator’s opinion, to potentially compromise subject safety or adversely affect the evaluation of efficacy, including (but not necessarily limited to) the following:
•Clinically significant hypotension or hypertension not stabilized by medical therapy
•Unstable thyroid dysfunction in the past 6 months
• Insufficiently controlled diabetes mellitus in the judgment of the investigator
•Clinically significant renal insufficiency
•Malignant tumor within the last 5 years
•Neurologic conditions including the following:
−History of seizure disorder or condition associated with seizures
−History of brain tumor, subdural hematoma or other clinically significant neurological condition within the past 12 months
−Head trauma with loss of consciousness within 12 months before screening
−Active acute or chronic central nervous system infection
−Stroke within 6 months before screening
•Cardiac conditions including the following:
•Clinically significant cardiac arrhythmia, cardiomyopathy, or cardiac conduction defect, history of myocardial infarction or unstable angina within the last 3 months before screening, or clinically significant abnormality on screening or baseline ECG including but not limited to the following:
−QTcF >465 msec if male or >485 msec if female
9. Laboratory abnormality that, in the opinion of the investigator, or any of the following laboratory abnormalities at screening or baseline:
•Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value ≥2 times the upper limit of the laboratory normal reference range
•Hemoglobin A1c (HbA1c) >9%
• Absolute neutrophil count ≤ 1.5 × 103 μL
•Platelet count ≤ 75 × 103 μL
•Serum creatinine > 2.5 mg/dL
•Positive test result for human immunodeficiency virus, hepatitis B surface antigen, or anti-hepatitis C virus antibody
•Positive pregnancy test result
•Urine drug screen at screening or baseline shows a positive result for any of the tested substances
−Exception: results positive for benzodiazepine or opiates may not be exclusionary if the investigator confirms that such medication was medically indicated and consults the INC Research medical monitor before enrolling a subject with such a finding.
10. Pregnant, lactating, or breastfeeding
11. Inadequate gluteal muscle or excessive gluteal fat, as determined by the investigator, that would interfere with gluteal IM injection using a 1.5- or 2-inch needle
12. Receipt of any long-acting antipsychotic medication by IM injection within 60 days before screening
13. Use of a prohibited medication
14. Current involuntary hospitalization or incarceration
15. Hospitalized for more than 30 days during the 90 days before screening
16. Participation in another clinical trial in which the subject received an experimental or investigational drug or agent within 6 months before screening
17. Participation in a clinical study with ALKS 9072 at any time
18. Study site personnel and/or persons employed by Alkermes or INC Research or by the investigator or study site, or is an immediate family member of such persons

E.5 End points

E.5.1

Primary end point(s)

•PANSS total score change from baseline to Day 85
(PANSS total score is defined as the sum of scores on the PANSS positive, negative, and general psychopathology subscale)

E.5.1.1

Timepoint(s) of evaluation of this end point

Screening, Day 1, Day 8, Day 15, Day 22, Day 29, Day 57,Day 85

E.5.2

Secondary end point(s)

• Clinician Global Impression - Improvement (CGI-I) scores at Day 85

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 8, Day 15, Day 22, Day 29, Day 57,Day 85

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

Yes

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

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)

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

Yes

E.8.2.3.1

Comparator description

2 different doses of ALKS 9072

E.8.2.4

Number of treatment arms in the trial

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

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

Bulgaria

Philippines

Malaysia

Romania

Russian Federation

Ukraine

Serbia

United States

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

LVLS

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.1.2.1

Number of subjects for this age range:

450

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

100

F.4.2.2

In the whole clinical trial

540

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)

According to the standard of care and based on the treating physician judgement.
Another option is subjects who successfully complete the Day 85 visit of the study ALK9072-003 and continue to meet eligibility criteria and sign an informed consent form are eligible to enroll in an extension study under protocol ALK9072-003EXT.

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

2013-02-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-03-11

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