Extension Study of the Safety and Efficacy of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Depression Clinical Trial

Official title:

A 6-Month, Open-Label, Flexible-Dosage (150 to 200 mg/Day) Extension Study of the Safety and Efficacy of Armodafinil Treatment as Adjunctive Therapy in Adults With Major Depression Associated With Bipolar I Disorder

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01121536
• Other study ID #: C10953/3074
• Secondary ID: 2009-016648-38
• Status: Terminated
• Phase: Phase 3
• Start date: April 30, 2010
• Est. completion date: October 31, 2013

Study information

• Verified date: August 2018
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 867
• Est. completion date: October 31, 2013
• Est. primary completion date: October 31, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

• 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.

• 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.

• 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; olanzapine; quetiapine; aripiprazole; lamotrigine; risperidone; ziprasidone, (only if taken in combination with lithium, valproic acid, or lamotrigine). The following criteria must also be met:

1. 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.

2. The patient may be taking 2 protocol-allowed mood stabilizers only if 1 of the drugs is lithium, valproic acid, or lamotrigine.

3. The patient must be judged by the investigator to be compliant with treatment with the mood stabilizer(s).

4. The patient must be willing to continue treatment with the same protocol-allowed mood stabilizer(s) at dosages considered appropriate by the investigator.

• The patient has a Young Mania Rating Scale (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.

Key Exclusion Criteria:

• 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.

• The patient has psychotic symptoms or had psychosis during the double-blind study.

• 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.

• The patient met criteria for alcohol or substance abuse or dependence (with the exception of nicotine dependence) during the double-blind study.

• The patient has any history of homicidal ideation or significant aggression or currently has homicidal or significant aggressive ideation.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Armodafinil
Armodafinil tablets, taken orally, once daily in the morning

Locations

Country	Name	City	State
Argentina	Teva Investigational Site 134	Buenos Aires
Argentina	Teva Investigational Site 136	Buenos Aires
Argentina	Teva Investigational Site 235	Buenos Aires
Argentina	Teva Investigational Site 237	Buenos Aires
Argentina	Teva Investigational Site 450	Buenos Aires
Argentina	Teva Investigational Site 462	Buenos Aires
Argentina	Teva Investigational Site 881	Buenos Aires
Argentina	Teva Investigational Site 884	Buenos Aires
Argentina	Teva Investigational Site 135	Cordoba
Argentina	Teva Investigational Site 236	Cordoba
Argentina	Teva Investigational Site 371	La Plata
Argentina	Teva Investigational Site 138	La Plata, Buenos Aires
Argentina	Teva Investigational Site 238	Rosario
Australia	Teva Investigational Site 141	Brisbane
Australia	Teva Investigational Site 240	Malvern
Brazil	Teva Investigational Site 624	Rio de Janeiro
Bulgaria	Teva Investigational Site 248	Bourgas
Bulgaria	Teva Investigational Site 146	Kardzhali
Bulgaria	Teva Investigational Site 148	Kazanlak
Bulgaria	Teva Investigational Site 853	Pazardjik
Bulgaria	Teva Investigational Site 852	Pleven
Bulgaria	Teva Investigational Site 145	Plovdiv
Bulgaria	Teva Investigational Site 249	Plovdiv
Bulgaria	Teva Investigational Site 370	Ruse
Bulgaria	Teva Investigational Site 147	Sofia
Bulgaria	Teva Investigational Site 247	Sofia
Bulgaria	Teva Investigational Site 854	Sofia
Bulgaria	Teva Investigational Site 855	Sofia
Bulgaria	Teva Investigational Site 245	Varna
Bulgaria	Teva Investigational Site 851	Varna
Canada	Teva Investigational Site 198	Kelowna
Canada	Teva Investigational Site 196	Mississauga
Canada	Teva Investigational Site 296	Mississauga
Canada	Teva Investigational Site 299	Penticton
Croatia	Teva Investigational Site 635	Rijeka
Croatia	Teva Investigational Site 633	Zagreb
Croatia	Teva Investigational Site 634	Zagreb
France	Teva Investigational Site 286	Dole
France	Teva Investigational Site 153	Nimes
Germany	Teva Investigational Site 655	Achim
Germany	Teva Investigational Site 651	Dresden
Hungary	Teva Investigational Site 661	Budapest
Hungary	Teva Investigational Site 662	Budapest
Hungary	Teva Investigational Site 664	Budapest
Hungary	Teva Investigational Site 666	Nagykallo
Italy	Teva Investigational Site 688	Catania
Italy	Teva Investigational Site 689	Firenze
Italy	Teva Investigational Site 687	Pisa
Italy	Teva Investigational Site 692	Rome
Poland	Teva Investigational Site 259	Bialystok
Poland	Teva Investigational Site 257	Gdansk
Poland	Teva Investigational Site 258	Gdansk
Poland	Teva Investigational Site 156	Kielce
Poland	Teva Investigational Site 155	Krakow
Poland	Teva Investigational Site 256	Leszno
Poland	Teva Investigational Site 255	Skorzewo
Poland	Teva Investigational Site 861	Szczecin
Poland	Teva Investigational Site 157	Tuszyn
Serbia	Teva Investigational Site 175	Belgrade
Serbia	Teva Investigational Site 177	Belgrade
Serbia	Teva Investigational Site 831	Belgrade
Serbia	Teva Investigational Site 832	Belgrade
Serbia	Teva Investigational Site 833	Belgrade
Serbia	Teva Investigational Site 176	Kragujevac
Serbia	Teva Investigational Site 837	Nis
Serbia	Teva Investigational Site 834	Novi Knezevac
Slovakia	Teva Investigational Site 699	Bratislava
Slovakia	Teva Investigational Site 697	Rimavska Sobota
Slovakia	Teva Investigational Site 696	Roznava
Slovakia	Teva Investigational Site 698	Trencin
South Africa	Teva Investigational Site 709	Cape Town
South Africa	Teva Investigational Site 712	Cape Town
South Africa	Teva Investigational Site 708	Centurion
South Africa	Teva Investigational Site 710	Johannesburg
South Africa	Teva Investigational Site 711	Paarl
South Africa	Teva Investigational Site 706	Pretoria
Spain	Teva Investigational Site 336	Alcoy
Spain	Teva Investigational Site 434	Coslada (Madrid)
Spain	Teva Investigational Site 433	Vitoria
Spain	Teva Investigational Site 430	Vitoria-Gasteiz
Ukraine	Teva Investigational Site 181	Dnipropetrovsk
Ukraine	Teva Investigational Site 872	Donetsk
Ukraine	Teva Investigational Site 282	Kharkiv
Ukraine	Teva Investigational Site 281	Kiev
Ukraine	Teva Investigational Site 180	Lugansk
Ukraine	Teva Investigational Site 873	Lviv
Ukraine	Teva Investigational Site 280	Odessa
Ukraine	Teva Investigational Site 875	Odessa
Ukraine	Teva Investigational Site 183	Poltava
Ukraine	Teva Investigational Site 871	S. Oleksandrivka
Ukraine	Teva Investigational Site 184	Simferopol
Ukraine	Teva Investigational Site 182	Vinnytsya
United States	Teva Investigational Site 193	Albuquerque	New Mexico
United States	Teva Investigational Site 406	Allentown	Pennsylvania
United States	Teva Investigational Site 229	Anaheim	California
United States	Teva Investigational Site 116	Atlanta	Georgia
United States	Teva Investigational Site 205	Atlanta	Georgia
United States	Teva Investigational Site 111	Austin	Texas
United States	Teva Investigational Site 190	Beachwood	Ohio
United States	Teva Investigational Site 100	Bellevue	Washington
United States	Teva Investigational Site 113	Birmingham	Alabama
United States	Teva Investigational Site 225	Birmingham	Alabama
United States	Teva Investigational Site 104	Brooklyn	New York
United States	Teva Investigational Site 207	Brooklyn	New York
United States	Teva Investigational Site 213	Canton	Ohio
United States	Teva Investigational Site 217	Cerritos	California
United States	Teva Investigational Site 223	Cerritos	California
United States	Teva Investigational Site 610	Cincinnati	Ohio
United States	Teva Investigational Site 102	Dayton	Ohio
United States	Teva Investigational Site 403	DeSoto	Texas
United States	Teva Investigational Site 290	Flowood	Mississippi
United States	Teva Investigational Site 612	Friendswood	Texas
United States	Teva Investigational Site 131	Gainesville	Florida
United States	Teva Investigational Site 115	Garden Grove	California
United States	Teva Investigational Site 228	Houston	Texas
United States	Teva Investigational Site 121	Imperial	California
United States	Teva Investigational Site 224	Irving	Texas
United States	Teva Investigational Site 132	Jacksonville	Florida
United States	Teva Investigational Site 606	Jacksonville Beach	Florida
United States	Teva Investigational Site 613	Kirkland	Washington
United States	Teva Investigational Site 600	Lafayette	Indiana
United States	Teva Investigational Site 127	Lauderhill	Florida
United States	Teva Investigational Site 117	Media	Pennsylvania
United States	Teva Investigational Site 106	Memphis	Tennessee
United States	Teva Investigational Site 103	Mount Laurel	New Jersey
United States	Teva Investigational Site 212	Mount Laurel	New Jersey
United States	Teva Investigational Site 107	Naperville	Illinois
United States	Teva Investigational Site 301	Naperville	Illinois
United States	Teva Investigational Site 202	New York	New York
United States	Teva Investigational Site 119	North Miami	Florida
United States	Teva Investigational Site 219	Oakbrook Terrace	Illinois
United States	Teva Investigational Site 303	Oceanside	California
United States	Teva Investigational Site 400	Oceanside	California
United States	Teva Investigational Site 401	Oklahoma City	Oklahoma
United States	Teva Investigational Site 609	Oklahoma City	Oklahoma
United States	Teva Investigational Site 616	Oklahoma City	Oklahoma
United States	Teva Investigational Site 409	Orem	Utah
United States	Teva Investigational Site 195	Park Ridge	Illinois
United States	Teva Investigational Site 200	Pico Rivera	California
United States	Teva Investigational Site 300	Pikesville	Maryland
United States	Teva Investigational Site 105	Raleigh	North Carolina
United States	Teva Investigational Site 404	Richmond	Virginia
United States	Teva Investigational Site 129	Rochester	New York
United States	Teva Investigational Site 133	Saint Louis	Missouri
United States	Teva Investigational Site 408	Salt Lake City	Utah
United States	Teva Investigational Site 128	San Diego	California
United States	Teva Investigational Site 201	San Diego	California
United States	Teva Investigational Site 192	Santa Ana	California
United States	Teva Investigational Site 292	Santa Ana	California
United States	Teva Investigational Site 295	Sherman Oaks	California
United States	Teva Investigational Site 204	Smyrna	Georgia
United States	Teva Investigational Site 605	Spokane	Washington
United States	Teva Investigational Site 110	Staten Island	New York
United States	Teva Investigational Site 411	Staten Island	New York
United States	Teva Investigational Site 118	Tampa	Florida
United States	Teva Investigational Site 608	Tampa	Florida
United States	Teva Investigational Site 122	Temecula	California
United States	Teva Investigational Site 603	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Croatia,  France,  Germany,  Hungary,  Italy,  Poland,  Serbia,  Slovakia,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants With Treatment-Emergent Adverse Events (TEAE)	AEs were graded by the investigator for severity on a three-point scale: mild, moderate and severe. Causality is graded as either related or not related. A serious adverse event (SAE) is an AE resulting in death, a life-threatening adverse event, hospitalization, a persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may require medical intervention to prevent any of the previous results.; Protocol-defined adverse events requiring expedited reporting included skin rash, hypersensitivity reaction, emergent suicidal ideation or suicide attempt, and psychosis.	Day 1 up to Month 6
Primary	Participants With Clinically Significant Abnormal Serum Chemistry Values	Summary of serum chemistry tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row.; ULN=upper limit of normal; BUN=Blood Urea Nitrogen; Uric acid has a normal range of 125-494 µmol/L. Criterion for clinically significant abnormal are different for men and women.; GGT = gamma-glutamyl transpeptidase with a normal range of 4-61 U/L; ALT = alanine aminotransferase with a normal range of 6-43 U/L; BUN = blood urea nitrogen with a normal range of 1.4-8.6 mmol/L; AST = aspartate aminotransferase with a normal range of 9-36 U/L	Day 1 to Month 6
Primary	Participants With Clinically Significant Abnormal Hematology Values	Summary of hematology tests in which at least one participant had a during study value that was clinically significant abnormal. The test name and criterion for clinically significant abnormal appear in each row.; ULN=upper limit of normal; WBC - white blood cell counts with a normal range of 3.8-10.7 10^9/L.; Hemoglobin with a normal range of 115-181 g/L; Hematocrit with a normal range of 0.34-0.54 L/L; Platelet counts with a normal range of 130-400 10^9/L; ANC= absolute neutrophil counts with a normal range of 1.96-7.23 10^9/L	Day 1 to Month 6
Primary	Participants With Clinically Significant Abnormal Urinalysis Values	Summary of urinalysis tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal urinalysis tests was >=2 unit increase from baseline.	Day 1 to Month 6
Primary	Participants With Clinically Significant Abnormal Vital Signs Values	Summary of vital signs tests in which at least one participant had a during study value that was clinically significant abnormal. Criterion for clinically significant abnormal vital signs are based on FDA Neuropharmacological Division criteria: Pulse high: >=120 beats per minute (bpm) and increase of >=15 bpm from baseline; Pulse low: <=50 bpm and decrease of >=15 bpm from baseline; Sitting systolic blood pressure high: >=180 mm Hg and increase of >=20 mm Hg from baseline; Sitting systolic blood pressure low: <=90 mm Hg and decrease of >=20 mm Hg from baseline; Sitting diastolic blood pressure high: >=105 mm Hg and increase of >=15 mm Hg from baseline; Sitting diastolic blood pressure low: <=50 mm Hg and decrease of >=15 mm Hg from baseline	Day 1 to Month 6
Primary	Change From Baseline to Endpoint in Electrocardiogram (ECG) Values	ECG was conducted at baseline which was before the first dose of study drug in the double-blind study, and at the month-6 visit of the open-label study (or early termination).; RR= inter-beat intervals	Day 0 (baseline), Month 6 or last post-baseline observation
Primary	Physical Examination Shifts From Baseline to Endpoint	Baseline is the day prior to double-blind treatment. Assessments are summarized as normal or abnormal. The first assessment is the baseline assessment followed by the endpoint assessment. For example 'normal/abnormal' indicates participants who were normal at baseline and abnormal at endpoint.; HEENT = Head, Eye, Ear, Nose and Throat exam	Day 0 (baseline), Month 6 (or last post-baseline observation)
Primary	Change From Baseline to Endpoint in Body Weight	Baseline was the score before the first dose of study drug in the double-blind study.	Day 0 (baseline), Month 6 (or last post-baseline observation)
Primary	Change From Baseline to Endpoint in the Young Mania Rating Scale (YMRS) Total Score	The YMRS is a clinician-rated, 11-item checklist used to measure the severity of manic episodes. Information for assigning scores is gained from the participant's subjective reported symptoms over the previous 48 hours and from clinical observation during the interview. Seven items are ranked 0 through 4 and have descriptors associated with each severity level. Four items (irritability, speech, content, and disruptive-aggressive behavior) are scored 0 through 8 and have descriptors for every second increment. The total scale is 0-60. A score of =12 indicates remission of manic symptoms, and higher scores indicate greater severity of mania. Negative change from baseline scores indicate a decrease in severity of mania.; Baseline was the score before the first dose of study drug in the double-blind study.	Day 0 (baseline), Month 6 or last post-baseline observation
Primary	Participants With Findings During the Open-Label Study on the Columbia-Suicide Severity Rating Scale 'Since Last Visit' Version (C-SSRS-SLV)	The C-SSRS is a clinician-rated scale that assesses suicidality from ideation to behaviors and monitors the potential emergence of suicidality in clinical studies. The number of participants who had findings on any of the C-SSRS-SLV (SLV=since last visit) categories at any of the time frames are indicated.; - C-SSRS=Columbia Suicide Severity Rating Scale	Day 1, Week 1, Months 1, 2, 4 and 6 or last post-baseline visit
Primary	Change From Baseline to Endpoint in the Insomnia Severity Index (ISI) Total Score	The ISI is a participant-rated, 7-item questionnaire designed to assess the severity of the participant's insomnia. Each item is ranked 0 (none) through 4 (very severe) and has a descriptor associated with each severity level. Total range is 0 (no insomnia) to 28 (very severe insomnia). Responses to each item are added to obtain a total score to determine the severity of insomnia. Negative change from baseline scores indicate a decrease in severity of insomnia. Baseline was the assessment before the first dose of study drug in the double-blind study.	Day 0 (baseline), Month 6 (or last post-baseline observation)
Primary	Change From Baseline to Endpoint in the Hamilton Anxiety Scale (HAM-A) Total Score	HAM-A measures the severity of anxiety symptoms. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Negative change from baseline scores indicate a decrease in severity of anxiety.; Baseline was the score before the first dose of study drug in the double-blind study.	Day 0 (baseline), Month 6 or last post-baseline observation
Secondary	Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 30-Item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30)	The IDS-C30 is a standardized 30-item, clinician-rated scale to assess the severity of a participant's depressive symptoms. Every effort was made to have the same rater evaluate a participant across all visits.; Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression.; Baseline was the score before the first dose of study drug in the double-blind study.	Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)
Secondary	Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Total Score From the 16-Item Quick Inventory of Depressive Symptomatology-Clinician-Rated (QIDS-C16)	The QIDS-C16 was derived from specified items in the IDS-C30, clinician-rated scale to assess the severity of a participant's depressive symptoms. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating the most severe depression. Negative change from baseline values indicate improvement in the severity of depression.; Baseline was the score before the first dose of study drug in the double-blind study.	Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)
Secondary	Change From Baseline to Week 1 and Months 1, 2, 4, 6 and Endpoint in the Clinical Global Impression of Severity (CGI-S) for Depression	The CGI-S is an observer-rated scale that measures illness severity on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). Negative change from baseline values indicate improvement in the severity of depression.; Baseline was the score before the first dose of study drug in the double-blind study.	Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)
Secondary	Change From Baseline to Endpoint in the Global Assessment for Functioning (GAF) Scale	The Global Assessment of Functioning (GAF) is a numeric scale (1 through 100) used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of adults, e.g., how well or adaptively one is meeting various problems-in-living. Ratings of 1 - 10 mean the participant is in persistent danger of severely hurting self or others (e.g., recurrent violence) or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death. Ratings of 91 - 100 indicate no symptoms, and the participant exhibits superior functioning in a wide range of activities, life's problems never seem to get out of hand, is sought out by others because of his or her many positive qualities. Positive change from baseline values indicate improvement in functioning.; Baseline was the score before the first dose of study drug in the double-blind study.	Day 0 (baseline), Month 6 or the last post-baseline assessment)