Clinical trial NCT00976560: Clinical Study to Test a New Drug to Treat Major Depression
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Keywords: Lack of interest and energy
Psychomotor retardation
Cytokines
Major Depressive disorder
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-09-14
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key Inclusion Criteria:

* 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

Key Exclusion Criteria:

* 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

Primary outcomes:
measure: 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.
timeFrame: At Week 6
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 6 Weeks
measure: Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score
timeFrame: Upto Week 6
measure: Number of Participants With Abnormal Haematology and Clinical Chemistry Values
timeFrame: Upto Week 6
measure: Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate)
timeFrame: Up to follow-up Visit (Day 53)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to follow-up Visit (Day 53)
measure: 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
timeFrame: Upto Week 6
measure: Change From Randomisation Bech Total Score: Bech Score
timeFrame: Up to Follow-up visit (Day 53)
measure: Mean HAMD-17 Total Score
timeFrame: Up to Follow-up visit (Day 53)
measure: Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score
timeFrame: Up to Follow-up visit (Day 53)
measure: Mean IDS-SR Total Score
timeFrame: Up to Week 6
measure: 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)
timeFrame: Weeks 0, 2, 4 and 6
measure: Percentage of IDS-C Responders (Participants With a Reduction in Total Score of ≥50% From Randomization at Week 6/Study Exit).
timeFrame: Week 6
measure: Percentage of IDS-C Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
timeFrame: Week 6
measure: Percentage of IDS-SR Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
timeFrame: Week 6
measure: Percentage of IDS-SR Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
timeFrame: Week 6
measure: Percentage of QIDS-SR16 Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
timeFrame: Week 6
measure: Percentage of QIDS-SR16 Remitters (Subjects Whose Total Score Was ≤ 5 at Week 6/Study Exit).
timeFrame: Week 6
measure: Percentage of Bech Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
timeFrame: Week 6
measure: Percentage of Bech Remitters (Participants Whose Total Score Was ≤ 4 at Week 6/Study Exit).
timeFrame: Week 6
measure: 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.
timeFrame: Weeks 1, 2, 3, 4, 5 and 6
measure: Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks
timeFrame: Upto Week 6
Other outcomes:
Locations:
city: Hoffman Estates
country: United States
facility: GSK Investigational Site
state: Illinois
city: Park Ridge
country: United States
facility: GSK Investigational Site
state: Illinois
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Pazardzhik
country: Bulgaria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Ruse
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Huettenberg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Achim
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Westerstede
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bielefeld
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St-Petersburg
country: Russian Federation
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: