Last updated: 11/07/2018 05:32:18
Clinical Study to test a new drug to treat Major DepressionPKI113009
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
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:
Number of participants with adverse events
Timeframe: 6 Weeks
Number of participants with suicidality as assessed by the Columbia Suicidality Severity Rating scale score
Timeframe: Upto Week 6
Number of participants with abnormal haematology and clinical chemistry values
Timeframe: Upto Week 6
Number of participants with abnormal Vital signs (blood pressure, Heart rate)
Timeframe: Up to follow-up Visit (Day 53)
Number of participants with abnormal Electrocardiogram (ECG) findings
Timeframe: Up to follow-up Visit (Day 53)
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
Change from Randomisation Bech Total Score: Bech score
Timeframe: Up to Follow-up visit (Day 53)
Mean HAMD-17 Total Score
Timeframe: Up to Follow-up visit (Day 53)
Mean Inventory of Depressive Symptomatology clinician (IDS-C) total score
Timeframe: Up to Follow-up visit (Day 53)
Mean IDS-SR total score
Timeframe: Up to Week 6
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
Percentage of IDS-C responders (participants with a reduction in total score of ≥50% from Randomization at Week 6/study exit).
Timeframe: Week 6
Percentage of IDS-C remitters (participants whose total score was ≤ 15 at Week 6/study exit).
Timeframe: Week 6
Percentage of IDS-SR responders (participants with a reduction in total score of ≥ 50% from Randomization at Week 6/study exit).
Timeframe: Week 6
Percentage of IDS-SR remitters (participants whose total score was ≤ 15 at Week 6/study exit).
Timeframe: Week 6
Percentage of QIDS-SR16 responders (participants with a reduction in total score of ≥ 50% from Randomization at Week 6/study exit).
Timeframe: Week 6
Percentage of QIDS-SR16 remitters (subjects whose total score was ≤ 5 at Week 6/study exit).
Timeframe: Week 6
Percentage of Bech responders (participants with a reduction in total score of ≥ 50% from Randomization at Week 6/study exit).
Timeframe: Week 6
Percentage of Bech remitters (participants whose total score was ≤ 4 at Week 6/study exit).
Timeframe: Week 6
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
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks
Timeframe: Upto Week 6
Interventions:
Drug: GW856553
Other: Placebo
Enrollment:
128
Observational study model:
Not applicable
Primary completion date:
2010-07-07
Time perspective:
Not applicable
Clinical publications:
Amir Inamdar, Emilio Merlo-Pich, Michelle Gee, Clare Makumi, Prafull Mistry, Jon Robertson, Erik Steinberg, Stefano Zamuner, Susan Learned, Robert Alexander, Emiliangelo Ratti.Evaluation of antidepressant properties of p38 MAP kinase inhibitor losmapimod (GW856553) in adults with major depressive disorder: a report of 2 randomized, placebo-controlled double-blind, multicenter Phase II studies .J Psychopharmacol.2014;28(6):570-581
Medical condition
Depressive Disorder, Major
Product
losmapimod
Collaborators
Not applicable
Study date(s)
September 2009 to July 2010
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 60 years
Accepts healthy volunteers
No
- 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
- 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
Inclusion and exclusion criteria
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
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
Trial location(s)
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19053
Status
Study Complete
Location
GSK Investigational Site
Hoffman Estates, Illinois, United States, 60169
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10128
Status
Study Complete
Location
GSK Investigational Site
Bielefeld, Nordrhein-Westfalen, Germany, 33647
Status
Study Complete
Location
GSK Investigational Site
Westerstede, Niedersachsen, Germany, 26655
Status
Study Complete
Location
GSK Investigational Site
Park Ridge, Illinois, United States, 60068
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2010-07-07
Actual study completion date
2010-07-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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