A Multicenter, 52-week, Open-label Study to Assess the Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Patients With Major Depressive Disorder
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 173
- 主要终点
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs), Severe (Grade 3 or Higher) TEAEs, and Discontinuations From the Trial Due to TEAEs
研究概览
简要总结
This is a multicenter, 52-week, open-label study designed to assess the safety and tolerability of an oral aripiprazole/escitalopram combination therapy in outpatients with major depressive disorder (MDD). Enrollment into the study will be from eligible participants who have completed participation in Protocol 31-08-255 [NCT01111539], 31-08-256 [NCT01111552], or 31-08-263 [NCT01111565] ("rollover" participants).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 66 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who participated in Protocol 31-08-255, 31-08-256, or 31-08-263.
排除标准
- •Participants with a current need for involuntary commitment or who have been hospitalized ≤ 28 days of the Baseline Visit for the current major depressive episode.
- •Participants with a diagnosis of delirium, dementia, amnestic or other cognitive disorder, schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder, eating disorder (including anorexia nervosa or bulimia), obsessive compulsive disorder, panic disorder, or posttraumatic stress disorder.
- •Participants with a diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
- •Participants experiencing hallucinations, delusions, or any psychotic symptomatology in the current depressive episode.
- •Participants who have met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for substance abuse in the past 6 months (prior to the Baseline Visit) and/or dependence up to and including the past 12 months (prior to the Baseline Visit), including alcohol and benzodiazepines, but excluding caffeine and nicotine. Participants with two positive drug results for cocaine should be excluded from the study.
- •Participants with hypothyroidism or hyperthyroidism.
- •Participants with a significant risk of committing suicide based on history, investigator's judgment, and/or evaluation based on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders.
- •Participants with insulin-dependent diabetes mellitus (IDDM).
- •Participants with epilepsy or significant history of seizure disorders, except for a single childhood febrile seizure, post-traumatic, etc.
研究组 & 干预措施
Prior Aripiprazole/Escitalopram Combination Therapy
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the maximum tolerated dose (MTD) by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.
干预措施: Aripiprazole (Drug)
Prior Aripiprazole/Escitalopram Combination Therapy
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the maximum tolerated dose (MTD) by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.
干预措施: Escitalopram (Drug)
Prior Escitalopram
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.
干预措施: Aripiprazole (Drug)
Prior Escitalopram
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.
干预措施: Escitalopram (Drug)
Prior Aripiprazole
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.
干预措施: Aripiprazole (Drug)
Prior Aripiprazole
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.
干预措施: Escitalopram (Drug)
Prior Single-blind Escitalopram
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
干预措施: Aripiprazole (Drug)
Prior Single-blind Escitalopram
Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
干预措施: Escitalopram (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs), Severe (Grade 3 or Higher) TEAEs, and Discontinuations From the Trial Due to TEAEs
时间窗: From first dose up to 30 days post last dose (Up to approximately 40 weeks)
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-patient hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention. TEAE is defined as an adverse event that started after start of study drug treatment. The Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was used to determine the severity wherein Grade 1=mild AE, Grade 2=moderate AE, Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death related to AE.
次要结局
- Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score(Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before))
- Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score(Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before))
- Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities(Up to 40 weeks)
- Mean Change From Baseline in Laboratory Test Results: Hemoglobin A1c (HbA1c)(Baseline, Week 8, and End of the study visit (Week 43 or before))
- Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities(Up to 40 weeks)
- Mean Change From Baseline in Body Weight(Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before))
- Mean Change From Baseline in Body Mass Index (BMI)(Baseline, Week 26 and End of the study visit (Week 43 or before))
- Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities(Up to 40 weeks)
- Mean Change From Baseline in Laboratory Test Results: Prolactin(Baseline, Weeks 8, 26, and End of the study visit (Week 43 or before))
- Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline; Weeks 1, 2, 4, 6, 8, 14 and Last Visit (Week 43 or before))
- Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score(Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before))
- Mean Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) Overall General Subscore(Baseline, Week 8, 26 and End of the study visit (Week 43 or before))
- Number of Participants With Potentially Clinically Significant Physical Examination Findings(Up to 40 weeks)
- Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score(Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before))
- Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score(Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before))
- Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score(Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before))
- Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Total Score(Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before))
- Mean Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score(Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before))