Phase 2
N=128
Clinical Study to Test a New Drug to Treat Major Depression
Depressive Disorder, Major
Bottom Line
View on ClinicalTrials.gov: NCT00976560 ↗Enrolled (actual)
128
Serious AEs
1.6%
Results posted
Nov 2017
Primary outcome: Primary: 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. — -6.5; -5.6 Scores on scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GW856553 (Drug); Placebo (Other)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jul 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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. |
-6.5; -5.6 | — |
| SECONDARY Number of Participants With Adverse Events |
28; 26; 1; 1 | — |
| SECONDARY Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score |
55; 57; 54; 55; 49; 54 | — |
| SECONDARY Number of Participants With Abnormal Haematology and Clinical Chemistry Values |
1; 0; 1; 0 | — |
| SECONDARY Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate) |
1; 0; 1; 0 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings |
0; 0 | — |
| SECONDARY 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 |
-1.06; -0.27; -1.86; -1.57; -0.67; -0.96 | — |
| SECONDARY Change From Randomisation Bech Total Score: Bech Score |
-1.2; -1.6; -2.5; -2.2; -3.9; -3.4 | — |
| SECONDARY Mean HAMD-17 Total Score |
21.7; 21.2; 18.9; 19.7; 16.5; 17.8 | — |
| SECONDARY Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score |
39.7; 39.2; 35.2; 35.9; 30.9; 32.4 | — |
| SECONDARY Mean IDS-SR Total Score |
34.7; 38.1; 29.2; 32.8; 24.7; 27.5 | — |
| SECONDARY 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) |
18.0; 17.8; 13.0; 14.1; 10.6; 11.8 | — |
| SECONDARY Percentage of IDS-C Responders (Participants With a Reduction in Total Score of ≥50% From Randomization at Week 6/Study Exit). |
50; 41 | — |
| SECONDARY Percentage of IDS-C Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit). |
38; 18 | — |
| SECONDARY Percentage of IDS-SR Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit). |
49; 47 | — |
| SECONDARY Percentage of IDS-SR Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit). |
37; 19 | — |
| SECONDARY Percentage of QIDS-SR16 Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit). |
55; 45 | — |
| SECONDARY Percentage of QIDS-SR16 Remitters (Subjects Whose Total Score Was ≤ 5 at Week 6/Study Exit). |
31; 13 | — |
| SECONDARY Percentage of Bech Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit). |
62; 49 | — |
| SECONDARY Percentage of Bech Remitters (Participants Whose Total Score Was ≤ 4 at Week 6/Study Exit). |
38; 20 | — |
| SECONDARY 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. |
10; 8; 28; 14; 41; 39 | — |
| SECONDARY Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks |
0; 1.59; 0; 1.69; 1.96; 3.51 | — |
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
Data sourced from ClinicalTrials.gov (NCT00976560). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.