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

• Register: EUCTR
• Last refreshed on: 13 December 2021
• Main ID: EUCTR2009-016634-27-FR
• Date of registration: 29/03/2010
• Prospective Registration: Yes
• Primary sponsor: Cephalon, Inc.
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 03/06/2010
• Target sample size: 660
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016634-27
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, France, Spain

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 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), o
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 scr

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

Health Condition(s) or Problem(s) studied

Major Depression Associated With Bipolar I Disorder

Intervention(s)

Trade Name: Nuvigil
Product Name: Armodafinil
Product Code: Nuvigil
Pharmaceutical Form: Tablet
INN or Proposed INN: Armodafinil
CAS Number: 112111-43-0
Current Sponsor code: CEP-10953
Other descriptive name: R-modafinil
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 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).

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

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 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

For full details please refer to the Protocol.

Secondary ID(s)

C10953/3072

Ethics review

Status: Approved
Approval date: 03/06/2010
Contact:

Results

• Results available: Yes
• Date Posted: 16/11/2016
• Date Completed: 21/11/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-016634-27/results