Clinical Trials Register

Summary
EudraCT Number:	2009-016667-11
Sponsor's Protocol Code Number:	C10953/3071
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-02-15
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

France - ANSM

A.2

EudraCT number

2009-016667-11

A.3

Full title of the trial

A Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dosage Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 and 200 mg/day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

A.4.1

Sponsor's protocol code number

C10953/3071

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	Cephalon, 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
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	Yes
D.2.1.1.1	Trade name	Nuvigil
D.2.1.1.2	Name of the Marketing Authorisation holder	Cephalon Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	ARMODAFINIL
D.3.2	Product code	Nuvigil
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	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Armodafinil
D.3.9.1	CAS number	112111-43-0
D.3.9.2	Current sponsor code	CEP-10953
D.3.9.3	Other descriptive name	R-modafinil
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Armodafinil
D.3.9.1	CAS number	112111-43-0
D.3.9.2	Current sponsor code	CEP-10953
D.3.9.3	Other descriptive name	R-modafinil
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	50
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	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

Major Depression Associated With Bipolar I Disorder

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to determine whether armodafinil treatment, at dosages of 150 and 200 mg/day, is more effective than placebo treatment as adjunctive therapy to mood stabilizers for treatment of adults with major depression associated with bipolar I disorder. Efficacy will be assessed by the mean change from baseline in the total score from the 30 Item Inventory of Depressive Symptomatology–Clinician Rated (IDS C30).

E.2.2

Secondary objectives of the trial

• To evaluate the efficTo evaluate the efficacy of armodafinil treatment compared with placebo treatment as adjunctive therapy for adults who are experiencing a major depressive episode associated with bipolar I disorder
• To evaluate the change from baseline in the Clinical Global Impression of Severity (CGI-S) of depression rating for depression at weeks 1, 2, 4, 6, and 8, or last postbaseline observation
• To evaluate the efficacy of armodafinil treatment compared with placebo treatment on patient functioning as assessed by the Global Assessment of Functioning (GAF) Scale scores at weeks 4 and 8, or last postbaseline observation
• To evaluate the safety and tolerability of armodafinil treatment

for full details please refer to protocol.

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

Pharmacokinetic

E.3

Principal inclusion criteria

(a) The patient has a diagnosis of bipolar I disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM IV TR) criteria as determined by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition – Clinical Trials (SCID CT) and is currently experiencing a major depressive episode.
(b) The investigator has established, by medical record documentation or by history from the patient and at least 1 reliable informant, that the patient has had at least 1 previous manic or mixed episode, which resulted in functional impairment and was treated (or should have been treated) with a mood stabilizer or antipsychotic medication. (Note: A manic or mixed episode that was induced by an antidepressant or stimulant (prescribed or not) does not satisfy this criterion.)
(c) The patient has had no more than 6 mood episodes in the last year.
(d) The patient’s current major depressive episode must have started no less than 4 weeks and no more than 12 months prior to the screening visit.
(e) The patient is being treated at screening with 1 or 2 of the following drugs: lithium, valproic acid, and/or olanzapine, or is willing to begin treatment with 1 or 2 of the following drugs: lithium, valproic acid, and/or olanzapine. (NOTE: If a change in medication is made by the investigator, it should be made as medically indicated, ie, because the patient was not satisfied with their previous treatment due to either lack of efficacy or poor tolerability, and not for purposes of study inclusion.) The patient must have been on a minimum dose of olanzapine (≥5 mg/day) or maintained a minimum plasma concentration level of lithium (≥0.5 mEq/L) or valproic acid (≥50 µg/mL) for at least 4 weeks prior to the baseline visit. The patient is prepared to continue taking this dosage for the duration of the study (Note: Dosage adjustments after randomization are permitted if required to maintain these concentration levels of lithium or valproic acid at the discretion of the investigator.)
(f) The patient has been on a stable dosage of all other permitted medications (with the exception of medication to be used on an as needed basis) for 2 weeks prior to the baseline visit.
(g) The patient has a score of 13 or more on the QIDS-C16 at the screening and baseline visits. (Note: The QIDS C16 will be derived from specified items in the IDS C30.)
(h) The patient has a CGI-S rating (for depression) of 4 (moderately ill) or higher at the screening visits and at the baseline visit.
(i) The patient has a YMRS total score of 10 or less at the screening and baseline visits.
(j) The patient has a YMRS score of 0 or 1 on items 1 through 3 at the screening and baseline visits.
(k) Written informed consent is obtained.
(l) The patient is a man or woman 18 through 65 years of age.
(m) The patient is in good health (except for diagnosis of bipolar I disorder) as judged by the investigator, on the basis of medical and psychiatric history, medical examination, ECG, serum chemistry, hematology, and urinalysis.
(n) Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
(o) The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.
(p) The patient has permanent accommodations and means of being contacted by the study center.
(q) The patient understands that they may enroll in this clinical study only once and may not enroll in any other clinical study while participating in this trial.

E.4

Principal exclusion criteria

(a) The patient has any Axis I disorder apart from bipolar I disorder that was the primary focus of treatment within 6 months of the screening visit or during the screening period.
(b) The patient has psychotic symptoms or has had psychosis within 4 weeks of the screening visit or during the screening period.
(c) The patient has current active suicidal ideation, is at imminent risk of self harm, or has a history of significant suicidal ideation or suicide attempt at any time in the past that causes concern at present; or, at any time during the screening period or at baseline has a score of 2 or more for item 18 on the IDS C30.
(d) The patient has any history of homicidal ideation or significant aggression or currently has homicidal or significant aggressive ideation.
(e) The patient has a history of an eating disorder or obsessive compulsive disorder (OCD) within 6 months of the screening visit or during the screening period.
(f) The patient has a history of alcohol or substance abuse or dependence (with the exception of nicotine dependence) within 3 months of the screening visit or during the screening period.
(g) The patient has borderline personality disorder or antisocial personality disorder.
(h) The patient has any other Axis II disorder that could interfere with the conduct of the study.
(i) The patient has a HAM A score of 17 or more at the baseline visit.
(j) The patient has a history of any cutaneous drug reaction or drug hypersensitivity reaction, a history of any clinically significant hypersensitivity reaction, or a history of multiple clinically relevant allergies.
(k) The patient has a past or present seizure disorder (except history of a single febrile seizure), or a history of clinically significant head trauma (eg, brain damage) or of brain surgery.
(l) The patient has left ventricular hypertrophy or the patient has mitral valve prolapse and has experienced mitral valve prolapse syndrome.
(m) The patient has human immunodeficiency virus (HIV).
(n) The patient has any clinically significant uncontrolled medical condition, treated or untreated.
(o) In the judgment of the investigator, the patient has any clinically significant deviation from normal in the physical examination.
(p) The patient has 1 or more clinical laboratory test values outside the ranges specified.
(q) The patient any other clinically significant laboratory abnormality, without prior written approval by the medical monitor.
(r) The patient has a positive urine drug screen (UDS) for anything other than cannabis unless the investigator and medical monitor agree that there is an adequate medical (therapeutic) explanation and the patient has a negative UDS prior to randomization. Patients with a positive result for cannabis may be enrolled at the discretion of the medical monitor if the investigator determines that there is no cannabis abuse (according to DSM-IV-TR criteria). The investigator will also determine that there is no regular use of cannabis and that, after counseling, the patient agrees not to use cannabis during the study. In that case the patient does not have to have a second UDS negative for cannabis before randomization.
(s) The patient has received modafinil or armodafinil within the past 5 years, or the patient has a known sensitivity to any ingredients in the study drug tablets.
(t) The patient has previously participated in a clinical study with armodafinil or has used any investigational product within 90 days of screening.
(u) The patient has used any medication known to induce metabolism via CYP3A4/5 within 14 days prior to the baseline visit.
(v) The patient is using any exclusionary medication, or has used exclusionary medication within 1 week or 5 half lives of the drug and its active metabolites, whichever is longer, of the baseline visit.
(w) The patient has received electroconvulsive therapy (ECT) within 3 months of the screening visit.
(x) The patient is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)
(y) The patient has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
(z) The patient is unlikely to comply with the study protocol or is unsuitable for any other reason, as judged by the investigator or medical monitor.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy measure and endpoint for this study is the IDS C30 assessed at all postbaseline visits.

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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

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

As in protocol

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	33
F.4.2	For a multinational trial
F.4.2.1	In the EEA	99
F.4.2.2	In the whole clinical trial	660

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

2010-04-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-04-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-03-16

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