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

NCT01121536 | Terminated Phase 3 Results DMC

• 2 other identifiers: C10953/30742009-016648-38
• Study Type: interventional
• Target: 867
• Locations: 17 countries
• Sites: 158

Brief 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.

Conditions

Depression

Keywords

Bipolar I Disorder

Outcome Measures

Primary Outcomes (12)

• 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

• 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

• 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

• 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

• 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

• 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

• 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)

• 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)

• 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

• 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

• 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)

• 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 Outcomes (4)

• 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)

  Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

• 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)

  Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

• 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

  Day 0 (baseline), Week 1, Months 1, 2, 4, 6 and the last post-baseline assessment)

• Change From Baseline to Endpoint in the Global Assessment for Functioning (GAF) Scale

  Day 0 (baseline), Month 6 or the last post-baseline assessment)

Study Arms (1)

Armodafinil 150-200 mg/day

EXPERIMENTAL

Participants began taking armodafinil at a dosage of 50 mg/day; the dosage was increased by 50 mg/day on days 2 and 4, up to a dosage of 150 mg/day. At the discretion of the investigator, the dosage of armodafinil may be increased to 200 mg/day on day 6 or thereafter, and reduced to 150mg/day if the higher dose is not well tolerated. Treatment was administered for six months.

Drug: Armodafinil

Interventions

Armodafinil DRUG

Armodafinil tablets, taken orally, once daily in the morning

Also known as: CEP-10953, Nuvigil

Armodafinil 150-200 mg/day

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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, valproic acid, or lamotrigine.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (158)

Teva Investigational Site 113

Birmingham, Alabama, 35216, United States

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Teva Investigational Site 225

Birmingham, Alabama, 35226, United States

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Teva Investigational Site 229

Anaheim, California, 92804, United States

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Teva Investigational Site 217

Cerritos, California, 90703, United States

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Teva Investigational Site 223

Cerritos, California, 90703, United States

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Teva Investigational Site 115

Garden Grove, California, 92845, United States

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Teva Investigational Site 121

Imperial, California, 92251, United States

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Teva Investigational Site 303

Oceanside, California, 92056, United States

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Teva Investigational Site 400

Oceanside, California, 92056, United States

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Teva Investigational Site 200

Pico Rivera, California, 90660, United States

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Teva Investigational Site 128

San Diego, California, 92123, United States

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Teva Investigational Site 201

San Diego, California, 92126, United States

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Teva Investigational Site 192

Santa Ana, California, 92705, United States

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Teva Investigational Site 292

Santa Ana, California, 92705, United States

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Teva Investigational Site 295

Sherman Oaks, California, 91403, United States

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Teva Investigational Site 122

Temecula, California, 92591, United States

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Teva Investigational Site 131

Gainesville, Florida, 32607, United States

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Teva Investigational Site 132

Jacksonville, Florida, 32256, United States

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Teva Investigational Site 606

Jacksonville Beach, Florida, 32250, United States

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Teva Investigational Site 127

Lauderhill, Florida, 33319, United States

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Teva Investigational Site 119

North Miami, Florida, 33161, United States

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Teva Investigational Site 118

Tampa, Florida, 33613, United States

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Teva Investigational Site 608

Tampa, Florida, 33613, United States

Location

Teva Investigational Site 205

Atlanta, Georgia, 30308, United States

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Teva Investigational Site 116

Atlanta, Georgia, 30328, United States

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Teva Investigational Site 204

Smyrna, Georgia, 30080, United States

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Teva Investigational Site 107

Naperville, Illinois, 60563, United States

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Teva Investigational Site 301

Naperville, Illinois, 60563, United States

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Teva Investigational Site 219

Oakbrook Terrace, Illinois, 60181, United States

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Teva Investigational Site 195

Park Ridge, Illinois, 60068, United States

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Teva Investigational Site 600

Lafayette, Indiana, 47905, United States

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Teva Investigational Site 300

Pikesville, Maryland, 21208, United States

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Teva Investigational Site 603

Watertown, Massachusetts, 02472, United States

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Teva Investigational Site 290

Flowood, Mississippi, 39232, United States

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Teva Investigational Site 133

St Louis, Missouri, 63139, United States

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Teva Investigational Site 103

Mount Laurel, New Jersey, 08054, United States

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Teva Investigational Site 212

Mount Laurel, New Jersey, 08054, United States

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Teva Investigational Site 193

Albuquerque, New Mexico, 87109, United States

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Teva Investigational Site 207

Brooklyn, New York, 11201, United States

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Teva Investigational Site 104

Brooklyn, New York, 11235, United States

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Teva Investigational Site 202

New York, New York, 10023, United States

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Teva Investigational Site 129

Rochester, New York, 14618, United States

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Teva Investigational Site 411

Staten Island, New York, 10305, United States

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Teva Investigational Site 110

Staten Island, New York, 10312, United States

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Teva Investigational Site 105

Raleigh, North Carolina, 27609, United States

Location

Teva Investigational Site 190

Beachwood, Ohio, 44125, United States

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Teva Investigational Site 213

Canton, Ohio, 44718, United States

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Teva Investigational Site 610

Cincinnati, Ohio, 45267, United States

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Teva Investigational Site 102

Dayton, Ohio, 45408, United States

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Teva Investigational Site 401

Oklahoma City, Oklahoma, 73103, United States

Location

Teva Investigational Site 609

Oklahoma City, Oklahoma, 73112, United States

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Teva Investigational Site 616

Oklahoma City, Oklahoma, 73112, United States

Location

Teva Investigational Site 406

Allentown, Pennsylvania, 18104, United States

Location

Teva Investigational Site 117

Media, Pennsylvania, 19063, United States

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Teva Investigational Site 106

Memphis, Tennessee, 38119, United States

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Teva Investigational Site 111

Austin, Texas, 78756, United States

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Teva Investigational Site 403

DeSoto, Texas, 75115, United States

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Teva Investigational Site 612

Friendswood, Texas, 77546, United States

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Teva Investigational Site 228

Houston, Texas, 77090, United States

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Teva Investigational Site 224

Irving, Texas, 75062, United States

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Teva Investigational Site 409

Orem, Utah, 84058, United States

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Teva Investigational Site 408

Salt Lake City, Utah, 84107, United States

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Teva Investigational Site 404

Richmond, Virginia, 23230, United States

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Teva Investigational Site 100

Bellevue, Washington, 98007, United States

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Teva Investigational Site 613

Kirkland, Washington, 98033, United States

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Teva Investigational Site 605

Spokane, Washington, 99204, United States

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Teva Investigational Site 237

Buenos Aires, 1428, Argentina

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Teva Investigational Site 450

Buenos Aires, C1012AAU, Argentina

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Teva Investigational Site 881

Buenos Aires, C1058AAJ, Argentina

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Teva Investigational Site 884

Buenos Aires, C1117ABH, Argentina

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Teva Investigational Site 136

Buenos Aires, C1405BOA, Argentina

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Teva Investigational Site 134

Buenos Aires, C1425AHQ, Argentina

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Teva Investigational Site 235

Buenos Aires, C1425CDC, Argentina

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Teva Investigational Site 462

Buenos Aires, Argentina

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Teva Investigational Site 135

Córdoba, 5004ALB, Argentina

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Teva Investigational Site 236

Córdoba, X5009BIN, Argentina

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Teva Investigational Site 371

La Plata, 41515, Argentina

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Teva Investigational Site 138

La Plata, Buenos Aires, 01900, Argentina

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Teva Investigational Site 238

Rosario, 2000, Argentina

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Teva Investigational Site 141

Brisbane, 4053, Australia

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Teva Investigational Site 240

Malvern, 3144, Australia

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Teva Investigational Site 624

Rio de Janeiro, 22270-060, Brazil

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Teva Investigational Site 248

Burgas, 8000, Bulgaria

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Teva Investigational Site 146

Kardzhali, 06600, Bulgaria

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Teva Investigational Site 148

Kazanlak, 6100, Bulgaria

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Teva Investigational Site 853

Pazardzhik, 4400, Bulgaria

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Teva Investigational Site 852

Pleven, 5800, Bulgaria

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Teva Investigational Site 249

Plovdiv, 4000, Bulgaria

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Teva Investigational Site 145

Plovdiv, 4002, Bulgaria

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Teva Investigational Site 370

Rousse, 7003, Bulgaria

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Teva Investigational Site 147

Sofia, 1377, Bulgaria

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Teva Investigational Site 854

Sofia, 1431, Bulgaria

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Teva Investigational Site 855

Sofia, 1431, Bulgaria

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Teva Investigational Site 247

Sofia, 1632, Bulgaria

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Teva Investigational Site 851

Varna, 9002, Bulgaria

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Teva Investigational Site 245

Varna, 9010, Bulgaria

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Teva Investigational Site 198

Kelowna, V1Y 1Z9, Canada

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Teva Investigational Site 296

Mississauga, L5M 4N4, Canada

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Teva Investigational Site 196

Mississauga, L5M4N4, Canada

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Teva Investigational Site 299

Penticton, V2A 4M4, Canada

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Teva Investigational Site 635

Rijeka, 51000, Croatia

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Teva Investigational Site 633

Zagreb, 10090, Croatia

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Teva Investigational Site 634

Zagreb, 10090, Croatia

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Teva Investigational Site 286

Dole, 39100, France

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Teva Investigational Site 153

Nîmes, 30029, France

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Teva Investigational Site 655

Achim, 28832, Germany

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Teva Investigational Site 651

Dresden, 01307, Germany

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Teva Investigational Site 661

Budapest, 1032, Hungary

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Teva Investigational Site 664

Budapest, 1036, Hungary

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Teva Investigational Site 662

Budapest, 1083, Hungary

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Teva Investigational Site 666

Nagykálló, 4321, Hungary

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Teva Investigational Site 688

Catania, 95124, Italy

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Teva Investigational Site 689

Florence, 50134, Italy

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Teva Investigational Site 687

Pisa, 56126, Italy

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Teva Investigational Site 692

Rome, 00193, Italy

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Teva Investigational Site 259

Bialystok, 15-879, Poland

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Teva Investigational Site 258

Gdansk, 80-282, Poland

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Teva Investigational Site 257

Gdansk, 80952, Poland

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Teva Investigational Site 156

Kielce, 25-317, Poland

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Teva Investigational Site 155

Krakow, 31-526, Poland

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Teva Investigational Site 256

Leszno, 64-100, Poland

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Teva Investigational Site 255

Skorzewo, 60-185, Poland

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Teva Investigational Site 861

Szczecin, 71-460, Poland

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Teva Investigational Site 157

Tuszyn, 95-080, Poland

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Teva Investigational Site 832

Belgrade, 11 000, Serbia

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Teva Investigational Site 175

Belgrade, 11000, Serbia

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Teva Investigational Site 177

Belgrade, 11000, Serbia

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Teva Investigational Site 831

Belgrade, 11000, Serbia

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Teva Investigational Site 833

Belgrade, 11000, Serbia

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Teva Investigational Site 176

Kragujevac, 34000, Serbia

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Teva Investigational Site 837

Niš, 18000, Serbia

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Teva Investigational Site 834

Novi Kneževac, 23330, Serbia

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Teva Investigational Site 699

Bratislava, 82007, Slovakia

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Teva Investigational Site 697

Rimavská Sobota, 97901, Slovakia

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Teva Investigational Site 696

Rožňava, 04801, Slovakia

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Teva Investigational Site 698

Trenčín, 91101, Slovakia

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Teva Investigational Site 712

Cape Town, 7530, South Africa

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Teva Investigational Site 709

Cape Town, 7708, South Africa

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Teva Investigational Site 708

Centurion, 0046, South Africa

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Teva Investigational Site 710

Johannesburg, 2195, South Africa

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Teva Investigational Site 711

Paarl, 7646, South Africa

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Teva Investigational Site 706

Pretoria, 0181, South Africa

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Teva Investigational Site 336

Alcoy, 03804, Spain

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Teva Investigational Site 434

Coslada (Madrid), 28822, Spain

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Teva Investigational Site 433

Vitoria-Gasteiz, 01004, Spain

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Teva Investigational Site 430

Vitoria-Gasteiz, 01006, Spain

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Teva Investigational Site 181

Dnipropetrovsk, 49027, Ukraine

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Teva Investigational Site 872

Donetsk, 83099, Ukraine

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Teva Investigational Site 282

Kharkiv, 61068, Ukraine

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Teva Investigational Site 281

Kiev, 4080, Ukraine

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Teva Investigational Site 180

Luhansk, 91045, Ukraine

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Teva Investigational Site 873

Lviv, 79012, Ukraine

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Teva Investigational Site 280

Odesa, 65014, Ukraine

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Teva Investigational Site 875

Odesa, 65014, Ukraine

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Teva Investigational Site 183

Poltava, 36006, Ukraine

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Teva Investigational Site 871

S. Oleksandrivka, 65128, Ukraine

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Teva Investigational Site 184

Simferopol, 95006, Ukraine

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Teva Investigational Site 182

Vinnytsia, 21018, Ukraine

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MeSH Terms

Conditions

Depression

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Sponsor's Medical Expert

  Cephalon

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: May 12, 2010
• Study Start: April 30, 2010
• Primary Completion: October 31, 2013
• Study Completion: October 31, 2013
• Last Updated: September 21, 2018
• Results First Posted: January 26, 2015

Record last verified: 2018-08

Locations

CA (4); US (66); HU (4); ZA (6); AR (13); BR (1); SE (8); AU (2); IT (4); SL (4); ES (4); UA (12); CR (3); FR (2); BU (14); DE (2); PL (9)