An Exploratory, Multicenter, Placebo-controlled, Randomized, Double-blind Study to Investigate the Antidepressant Mechanism-of-action of JNJ-42847922 in Subjects With Major Depressive Disorder
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 11
- 主要终点
- Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Total Score
研究概览
简要总结
The purpose of this study is to explore if the magnitude of treatment effect (JNJ-42847922; placebo) on symptoms of depression (as measured by Hamilton rating scale for depression-17 [HDRS17], Sleep item-adjusted HDRS17, Anxiety/somatization factor score and the 6-item subscale from HDRS17 [HAM-D6]) differs across different levels of hyper-arousal status (characterized by Sleep parameters, ruminative response scale [RRS], Sleep and Worry visual analogue scale [VAS], quantitative electro-encephalography [qEEG], heart rate variability [HRV] and others).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a body mass index (BMI) between 18 and 35 kilogram per meter square (kg/m^2) inclusive (BMI = weight/height^2)
- •Participants must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and baseline
- •Population specific: Participant must meet Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-5) diagnostic criteria for MDD (international classification of diseases [ICD]-code F32.x and F33.x), without psychotic features, and confirmed by the Mini International Neuropsychiatric Interview (MINI) 7.0; have a Montgomery Asberg Depression Rating Scale (MADRS) total score greater than or equal to (>=) 25 at screening and must not demonstrate a clinically significant change (that is, an improvement of greater than (>) 20 percent (%) on their MADRS total score) from the screening to the second completion of MADRS by telephone at most 4 days before the baseline visit; Not currently receiving antidepressant drug therapy for >= 2 weeks before screening
- •Men who are sexually active with a women of childbearing potential (WOCBP) and have not had a vasectomy must agree to use a barrier method of birth control
- •A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose
- •A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after receiving the last dose of study drug
排除标准
- •Has failed more than 2 treatments (no more than 20 percent (%) response) with a differing pharmacological mode of action despite an adequate dose and duration during a previous, or the current depressive episode
- •Has a diagnosis of Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the Hypothalamus pituitary adrenal (HPA) axis
- •Is pregnant or breast feeding
- •Participant has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 60 days before the planned first dose of study drug, or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in an interventional study
- •Participant is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
- •Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
研究组 & 干预措施
Lead-in period: Placebo
Participants who successfully complete the baseline examination visit at the clinical site/unit, will be treated with placebo (2 capsules taken orally) for the duration of the lead-in period which will last up to 3 weeks. Investigators and participants will be blinded to exact duration of each participant-specific lead-in period throughout the study.
干预措施: Placebo (Drug)
Treatment period: JNJ-42847922 or Placebo
Placebo lead-in period responders and non-responders will be randomized to receive either placebo or 20 milligram (mg) JNJ-42847922 or 40 mg JNJ-42847922 for 5 Weeks. Participants will swallow JNJ-42847922 20 mg (2*10-mg capsules) or JNJ-42847922 40 mg (2*20-mg capsules) or 2 matching placebo capsules once daily for 5 Weeks.
干预措施: JNJ-42847922 20mg (Drug)
Treatment period: JNJ-42847922 or Placebo
Placebo lead-in period responders and non-responders will be randomized to receive either placebo or 20 milligram (mg) JNJ-42847922 or 40 mg JNJ-42847922 for 5 Weeks. Participants will swallow JNJ-42847922 20 mg (2*10-mg capsules) or JNJ-42847922 40 mg (2*20-mg capsules) or 2 matching placebo capsules once daily for 5 Weeks.
干预措施: JNJ-42847922 40mg (Drug)
Treatment period: JNJ-42847922 or Placebo
Placebo lead-in period responders and non-responders will be randomized to receive either placebo or 20 milligram (mg) JNJ-42847922 or 40 mg JNJ-42847922 for 5 Weeks. Participants will swallow JNJ-42847922 20 mg (2*10-mg capsules) or JNJ-42847922 40 mg (2*20-mg capsules) or 2 matching placebo capsules once daily for 5 Weeks.
干预措施: Placebo (Drug)
Withdrawal period: Placebo
Participants who will complete the treatment period prior to the end of Week 8 will enter the withdrawal period where they will be treated with placebo (2 capsules taken orally) for the remaining time of the double-blind phase of the study. Investigators and participants will be blinded to exact duration of each participant-specific withdrawal period.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Total Score
时间窗: Baseline up to Day 57
The HDRS17 is a Clinician-Administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a total score range of 0 to 52. It is the most widely used symptom severity measure for depression. Each of the 17 items is rated by the clinician on either a 3- point (0 to 2) or a 5-point scale (0 to 4). The point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Total score will be calculated by summing up the individual item score. The higher the score, the more severe the depression.
Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Sleep Item-Adjusted Total Score
时间窗: Baseline up to Day 57
The HDRS17 is a Clinician-Administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. It is the most widely used symptom severity measure for depression. Each of the 17 items is rated by the clinician on either a 3- point (0 to 2) or a 5-point scale (0 to 4). The point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. HDRS17 Sleep Item-Adjusted is derived from the HDRS17 scale excluding the 3 sleep items (4, 5, and 6) from the total score.
Change From Baseline in Hamilton Rating Scale for Depression-17 (HDRS17) Anxiety/Somatization Factor Score
时间窗: Baseline up to Day 57
The HDRS17 anxiety/somatization factor derived from Cleary and Guy's factor analysis of the HDRS scale, includes six items from the original 17-item version: the items for psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Anxious depression is often defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, as reflected in an anxiety/ somatization factor score greater than or equal to (\>=) 7. The score ranges from 0 to 18, with higher scores indicating greater severity of symptoms.
Change From Baseline in 6 Item Subscale From HDRS17 (HAM-D6) Score
时间窗: Baseline up to Day 57
The 6-Item Hamilton Depression Scale (HAMD-6), derived by the sum of HAMD-17 items (the six items in the HAM-D6 are: depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and general somatics \[tiredness and pains\]), evaluates "core" symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe). The higher the score, the more severe the depression.
次要结局
- Performance Score on a Cognitive Test Battery Evaluated by Word List Recall Test (WLRT)(Baseline)
- Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16)(Baseline up to Day 67)
- Association Between Major Depressive Disorder (MDD) Symptoms and Signals of Hyper-Arousal(Baseline up to Day 67)
- Performance Score on a Cognitive Test Battery Evaluated by Symbol Digit Matching Test (SDMaT)(Baseline)
- Performance Score on a Cognitive Test Battery Evaluated by Trail Making Test Form B (TMT-B)(Baseline)
- Change From Baseline in Bond & Lader (B&L) Visual Analogue Scale (VAS)(Baseline up to Day 57)
- Plasma Concentration of JNJ- 42847922 and its Metabolites(Day 36 to 40 (over 48 hours during Visit 6))
- Change From Baseline in Profile of Mood States (POMS)(Baseline up to Day 57)
- Percent Change From Baseline in Biomarker Levels(Day 36 to 40 (over 48 hours during Visit 6))
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability(Up to end of the study (Day 67))