A Six Week Randomized, Double-blind, Multi-center, Placebo-controlled, Exploratory, Adaptive Design Study to Explore the Antidepressant Properties of the p38 MAP Kinase Inhibitor GW856553 Compared to Placebo in Adult Subjects With Major Depressive Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- Change From Randomization (Week 0) Associated With GW856553 Versus Placebo at Week 6 in the Bech (6-item HAMD-17 [Hamilton Depression Rating Scale]) Score.
研究概览
简要总结
In this randomized, double-blind, multi-centre, placebo controlled, exploratory, adaptive design study, the antidepressant and plasma cytokine lowering effects of the GW856553 will be investigated in adult subjects diagnosed with MDD. Subjects will receive oral doses of GW856553 or placebo for six weeks. Safety, tolerability, pharmacokinetics and pharmacodynamics, defined as biomarkers in blood and clinical symptoms, will be assessed.
The primary endpoint is the change from baseline associated with GW856553 versus placebo at Week 6 in the Bech (6-item HAMD-17) score. Interim analyses of the primary endpoint will be performed throughout the study to potentially adapt the study design by changing the randomization ratio and/ or reducing the total number of subjects to be randomized into the study. Exploratory analyses will be performed by associating changes in cytokine levels and selected clinical symptoms; PK/PD modelling will also be used to identify the most sensitive clinical and biological markers.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects with primary diagnosis of moderate to severe MDD without psychotic features, for at least 4 weeks and one previous MDD episode
- •Males or Females who agree to use protocol specified contraception if of child bearing potential
- •BMI 18.5-35.0 kg/m2
- •Normal liver function tests
排除标准
- •History of liver disease or positive hepatitis B surface antigen or hepatitis C antibody in the last 3 months
- •Elevated liver function tests on >2 ocassions in the last 7 months
- •Significant medical illness, autoimmune disease or infectious disease
- •Pregnant or nursing females
- •Excessive and regular alcohol consumption
- •History of substance abuse or dependence in past 6 months or positive urine drug screen
- •Significant suicidal or homicidal risk
- •Currently receiving chronic biological or pharmacologic anti-inflammatory therapy or is not euthyroid
- •Psychoactive drugs within 1 week or 5 half lives of randomization visit
- •Treatment resistant subjects
研究组 & 干预措施
GW856553
GW856553 7.5 mg BID
干预措施: GW856553 (Drug)
Placebo
Matching Placebo BID
干预措施: Placebo (Other)
结局指标
主要结局
Change From Randomization (Week 0) Associated With GW856553 Versus Placebo at Week 6 in the Bech (6-item HAMD-17 [Hamilton Depression Rating Scale]) Score.
时间窗: At Week 6
HAMD-17 has 17 questions. The HAMD-17 Total Score was calculated by summing the individual response scores over the 17 individual components of the interview. The highest possible score was 52, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. There were 9 five point questions and 8 three point questions. The responses to the individual questions had values of 0-2 (three points response) or 0-4 (five points response). The BECH scale was extracted from the HAMD-17 and comprises of 6 items out of which 5 are 5 point questions and 1 is 3 point question. The Bech Total Score was calculated by summing the individual response scores and ranged from 0 to 22, with higher scores indicating more severe depression. Week 0 values were considered as Baseline.The change from randomization was analysed using suitable Bayesian mixed-effects model repeated measures (BMMRM) assuming missing at random (MAR).
次要结局
- Percentage of Participants With a Clinicians Global Impression of Improvement (CGI-I) Score of 1 ("Very Much Improved") or 2 ("Much Improved") at Weeks 1, 2, 3, 4, 5 and 6.(Weeks 1, 2, 3, 4, 5 and 6)
- Number of Participants With Abnormal Haematology and Clinical Chemistry Values(Upto Week 6)
- Number of Participants With Adverse Events(6 Weeks)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Up to follow-up Visit (Day 53))
- Percentage of IDS-SR Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).(Week 6)
- Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score(Upto Week 6)
- Changes From Randomization (Week 0)in IL-6 and TNF-alpha Associated With GW856553 Versus Placebo at Week 1 and Week 6 in the Morning Plasma Levels(Upto Week 6)
- Change From Randomisation Bech Total Score: Bech Score(Up to Follow-up visit (Day 53))
- Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score(Up to Follow-up visit (Day 53))
- Percentage of QIDS-SR16 Remitters (Subjects Whose Total Score Was ≤ 5 at Week 6/Study Exit).(Week 6)
- Percentage of Bech Remitters (Participants Whose Total Score Was ≤ 4 at Week 6/Study Exit).(Week 6)
- Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate)(Up to follow-up Visit (Day 53))
- Mean HAMD-17 Total Score(Up to Follow-up visit (Day 53))
- Mean Quick Inventory of Depressive Symptomatology Self Report-16 Item (QIDS-SR16) Total Score Derived From the IDS-SR (Only at Weeks 0, 2, 4 and 6)(Weeks 0, 2, 4 and 6)
- Percentage of IDS-C Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).(Week 6)
- Percentage of IDS-SR Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).(Week 6)
- Mean IDS-SR Total Score(Up to Week 6)
- Percentage of IDS-C Responders (Participants With a Reduction in Total Score of ≥50% From Randomization at Week 6/Study Exit).(Week 6)
- Percentage of QIDS-SR16 Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).(Week 6)
- Percentage of Bech Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).(Week 6)
- Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks(Upto Week 6)