The purpose of this study is to look at the safety, effectiveness, and tolerability of armodafinil when used with mood stabilizers in subjects with major depression associated with bipolar I disorder.

• Register: EUCTR
• Last refreshed on: 11 August 2014
• Main ID: EUCTR2010-023623-26-BG
• Date of registration: 18/04/2012
• Prospective Registration: Yes
• Primary sponsor: Cephalon, Inc.
• Public title: The purpose of this study is to look at the safety, effectiveness, and tolerability of armodafinil when used with mood stabilizers in subjects with major depression associated with bipolar I disorder.
• Scientific title: A Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dosage Study to Evaluate the Efficacy and Safety of Armodafinil Treatment (150 mg/day) as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder
• Date of first enrolment: 15/08/2012
• Target sample size: 370
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023623-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Brazil, Bulgaria, Croatia, Finland, Germany, Hungary, India, Italy, Poland, Slovakia, South Africa, United States

Contacts

• Name: Regulatory Affairs Department
• Affiliation: i3 Internation (UK)

• Name: Regulatory Affairs Department
• Affiliation: i3 Internation (UK)

Key inclusion & exclusion criteria

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 DSM-IV (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 2 weeks and no more than 12 months prior to the screening visit. The current depressive episode must have begun after the patient’s current mood stabilizer regime began. Date of onset of the current depressive episode
must be at least 8 weeks after resolution of any previous mood episode (ie, depressive, manic, hypomanic, or mixed episode).
(e) Inclusion criterion (e) was replaced by (e1).
(e1) The patient must have been taking 1 (or 2) of the following protocol-allowed mood stabilizers:
• lithium
• valproic acid
• lamotrigine
• aripiprazole
• olanzapine
• quetiapine
• risperidone
• ziprasidone (only if taken in combination with lithium, valproic acid, or lamotrigine)
The following criteria must also be met:
• The mood stabilizer(s) must have been taken a minimum 4 weeks before the onset of the major depressive episode and still be taken at the time of the screening visit at dose or blood level considered appropriate for maintenance therapy by the patient’s physician.
• The patient must continue to take the same mood stabilizer(s) during the screening period; no mood stabilizer may be added during the screening period.
• The mood stabilizer(s) must be taken for a minimum of 8 weeks prior to the baseline visit.
• The dosage of the mood stabilizer(s) must be stable for a minimum of 4 weeks prior to the baseline visit. Minimum required dosages and plasma concentrations, if applicable, and the lengths of time for these minimum requirements (4 or 8 weeks depending on the medication) are provided in the protocol.
• The mood stabilizer(s) must be taken in an oral formulation, with the exception of risperidone, which can be either in an oral or long-acting injection formulation.
• The patient may be taking 2 protocol-allowed mood stabilizers only if 1 of the drugs is lithium, valproic acid, or lamotrigine.
(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.
(h) The patient has a CGI-S rating (for depression) of 4 (moderately ill) or higher at the screening visit 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 w
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) Exclusion criterion (j) was replaced by (j1).
(j1) The patient has a history of any clinically significant cutaneous drug reaction or a history of clinically significant hypersensitivity reaction, including multiple 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 (q) The patient has 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 d

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Major Depression Associated With Bipolar I Disorder
MedDRA version: 16.0 Level: LLT Classification code 10004911 Term: Bipolar affective disorder, depressed System Organ Class: 100000004873

Intervention(s)

Product Name: Armodafinil
Product Code: CEP-10953
Pharmaceutical Form: Tablet
INN or Proposed INN: Armodafinil
CAS Number: 112111-43-0
Current Sponsor code: CEP-10953
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of the study is to determine whether armodafinil treatment, at a dosage of 150 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).

Secondary Objective: • To 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 CGI-S rating for depression at weeks 1, 2, 4, 6, 7, and 8, or last postbaseline observation.
• To evaluate the efficacy of armodafinil treatment compared with placebo treatment on patient functioning as assessed by the GAF Scale scores at weeks 4 and 8, or last postbaseline observation.
• To evaluate the safety and tolerability of armodafinil treatment.

Primary end point(s): The primary efficacy measure and endpoint for this study is the IDS-C30 assessed at all postbaseline visits.

Timepoint(s) of evaluation of this end point: All postbaseline visits.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • the IDS-C30 assessed at weeks 1, 2, 4, 6, 7, and 8, or last postbaseline observation
• CGI-S for depression assessed at weeks 1, 2, 4, 6, 7, and 8, or last postbaseline observation
• GAF Scale assessed at weeks 4 and 8, or last postbaseline observation

Secondary end point(s): The secondary efficacy measures and endpoints are as follows:

• the IDS-C30
• CGI-S for depression
• GAF Scale

Secondary ID(s)

C10953/3073

2010-023623-26-HU

Source(s) of Monetary Support

Cephalon, Inc