E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depression Associated With Bipolar I Disorder |
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E.1.1.1 | Medical condition in easily understood language |
Major Depression Associated With Bipolar I Disorder |
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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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004911 |
E.1.2 | Term | Bipolar affective disorder, depressed |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the safety and tolerability of long-term (6 months) armodafinil treatment as adjunctive therapy to mood-stabilizing medications in adults with bipolar I disorder whose most recent episode was a depressive episode. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate long-term efficacy of armodafinil 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) for depression to week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• To evaluate the efficacy of armodafinil treatment on patient functioning as assessed by the Global Assessment of Functioning (GAF) Scale scores at month 6 (or last postbaseline observation) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are included in the study if all of the following criteria are met (NOTE: All psychiatric diagnoses are made on the basis of DSM-IV-TR criteria.):
(a) The patient has completed 8 weeks of treatment in a Cephalon-sponsored Phase 3, double-blind study of armodafinil treatment in patients with major depression associated with bipolar I disorder.
(b) Inclusion criterion (b) was replaced by (b1).
(b1) The patient met criteria for enrollment in the previous double-blind study and, in the opinion of the investigator, is in need of continued treatment for depression.
(c) Inclusion criterion (c) was replaced by (c1), and (c1) was replaced by (c2).
(c2) During the previous double-blind study, the patient must have been taking 1 (or 2) of the following protocol-allowed mood stabilizers: lithium; valproic acid; aripiprazole; olanzapine; ziprasidone taken in combination with lithium or valproic acid; lamotrigine; or risperidone as described below.
― The mood stabilizers 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 or valproic acid.
― The patient must be judged by the investigator to be compliant with treatment with the mood stabilizer(s).
― The patient must be willing to continue treatment with the same
protocol-allowed mood stabilizer(s) at dosages considered appropriate by the investigator.
Minimum dosage requirements, if applicable, and the lengths of time they are required are provided in Table 3.
(d) The patient has a YMRS total score of 14 or less at the enrollment visit. Patients who have a YMRS score of 12 through 14 must be discussed with the medical monitor to determine their suitability for enrollment.
(e) Written informed consent is obtained.
(f) The patient is a man or woman 18 through 65 years of age at the time of enrollment in the double-blind study.
(g) 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 results.
(h) Inclusion criterion (h) was replaced by (h1).
(h1) Women of childbearing potential (women who have not reached menopause, women who are less than 2 years postmenopausal, and women who are not surgically sterile) who are sexually active 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, intrauterine device (IUD), and
steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
(i) The patient is willing and able to comply with study restrictions and to attend regularly scheduled clinic visits as specified in this protocol.
(j) The patient has permanent accommodations and means of being contacted by the study center.
(k) The patient agrees not to enroll in any other clinical study while participating in this study.
(l) The patient may temporarily reside in a clinic or hospital, or may currently be treated in an over-night medical facility at the beginning of and throughout the study, in a manner consistent with medical practices as related to the treatment of depression associated with bipolar I disorder. (NOTE: The patient must not require extended treatment due to the seriousness or worsening of symptoms; such patients are not appropriate for this trial [see exclusion criterion (p1)]). |
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E.4 | Principal exclusion criteria |
Patients are excluded from participating in this study if 1 or more of the following criteria are met (NOTE: All psychiatric diagnoses are made on the basis of DSM-IV-TR criteria.):
(a) The patient has any Axis I or Axis II disorder apart from bipolar I disorder that became the primary focus of treatment during the double-blind study.
(b) The patient has psychotic symptoms or had psychosis during the double-blind study.
(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 enrollment has a score of 2 or more for item 18 on the IDS-C30.
(d) The patient met criteria for alcohol or substance abuse or dependence (with the exception of nicotine dependence) during the double-blind study.
(e) The patient has any history of homicidal ideation or significant aggression or currently has homicidal or significant aggressive ideation.
(f) 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.
(g) 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.
(h) The patient has left ventricular hypertrophy or the patient has mitral valve prolapse and has experienced mitral valve prolapse syndrome.
(i) The patient has human immunodeficiency virus (HIV).
(j) The patient has any clinically significant uncontrolled medical condition, treated or untreated.
(k) In the judgment of the investigator, the patient has any clinically significant deviation from normal in the physical examination.
(l) The patient has evidence of current non-medical substance use on urine drug screen (UDS) or by history.
(m) The patient is a pregnant or lactating woman. (Any woman becoming pregnant during the study will be withdrawn from the study.)
(n) The patient has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (ADME) (including gastrointestinal surgery).
(o) 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.
(p) Exclusion criterion (p) is replaced by (p1).
(p1) The patient is an inpatient without consent or is institutionalized for reasons other than the conditions stipulated in inclusion criterion a. (NOTE: Also refer to inclusion criterion (l).) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy endpoints for this study are as follows:
• The IDS-C30
• The QIDS-C16
• The CGI-S for depression
• The GAF Scale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• The IDS-C30 assessed at week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• The QIDS-C16 (which will be derived from the IDS-C30) assessed at week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• The CGI-S for depression assessed at week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• The GAF Scale assessed at month 6 (or last postbaseline observation) |
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E.5.2 | Secondary end point(s) |
Safety endpoints are as follows:
• clinical laboratory tests (serum chemistry, hematology, and urinalysis)
• vital signs (blood pressure and pulse)
• ECGs
• physical examinations
• body weight
• concomitant medication usage
• YMRS
• C-SSRS-SLV
• ISI
• HAM-A |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• clinical laboratory tests (serum chemistry, hematology, and urinalysis) assessed at month 6 (or last postbaseline observation)
• vital signs (blood pressure and pulse) at week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• ECGs at month 6 (or last postbaseline observation)
• physical examinations at month 6 (or last postbaseline observation)
• body weight at month 6 (or last postbaseline observation)
• concomitant medication usage throughout study
• YMRS at week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• C-SSRS-SLV at week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• ISI at week 1 and months 1, 2, 4, and 6 (or last postbaseline observation)
• HAM-A at month 6 (or last postbaseline observation) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | No |
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 |
Brazil |
Croatia |
Czech Republic |
Finland |
Germany |
Hungary |
India |
Italy |
Slovakia |
South Africa |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |