Depressive Disorder, MajorPhase 2PKI113009NCT00976560
Clinical Study to Test a New Drug to Treat Major Depression
A Phase 2 study testing GW856553 in people with Depressive Disorder, Major, run by GlaxoSmithKline at 21 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Depressive Disorder, Major
- What is being tested?
- GW856553
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 128 participants
- Where
- 21 sitesin 5 countries
- Study dates
- 25 Sep 2009to 7 Jul 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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 locations and contacts
21 sites in 5 countries.
21 sites in 5 countries
Germany7 sites
GSK Investigational Site
Achim, Lower Saxony, 28832
GSK Investigational Site
Berlin, 10629
GSK Investigational Site
Bielefeld, North Rhine-Westphalia, 33647
GSK Investigational Site
Dresden, Saxony, 01097
GSK Investigational Site
Hüttenberg, Hesse, 35625
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, 19053
GSK Investigational Site
Westerstede, Lower Saxony, 26655
Russia5 sites
GSK Investigational Site
Moscow, 107076
GSK Investigational Site
Moscow, 125367
GSK Investigational Site
Saint Petersburg
GSK Investigational Site
Samara, 443016
GSK Investigational Site
Smolensk, 214 019
United States4 sites
GSK Investigational Site
Columbus, Ohio, 43210
GSK Investigational Site
Hoffman Estates, Illinois, 60169
GSK Investigational Site
New York, New York, 10128
GSK Investigational Site
Park Ridge, Illinois, 60068
Bulgaria4 sites
GSK Investigational Site
Pazardzhik, 4400
GSK Investigational Site
Plovdiv, 4000
GSK Investigational Site
Rousse
GSK Investigational Site
Sofia, 1113
About this study
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
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.
- Conditions
- Depressive Disorder, Major
- Being tested
- GW856553, Placebo
- Keywords
- Lack of interest and energy, Psychomotor retardation, Cytokines, Major Depressive disorder
- Medical subject headings
- Depressive Disorder, Major, Psychomotor Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GW856553Drug
Wet Granulated, film coated white, 9mm round, biconvex, plain faced tablets, containing 7.5 mg of GW856553
PlaceboOther
Film coated white, 9mm round, biconvex, plain faced tablets obtained by direct compression.
| Study group | Role | What they receive |
|---|---|---|
| GW856553 | Experimental | GW856553 7.5 mg BID Receives: Drug: GW856553 |
| Placebo | Placebo comparator | Matching Placebo BID Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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).
Measured: At Week 6
Secondary outcomes (21)
Number of Participants With Adverse Events
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. The AEs row include participants with SAEs.
Measured: 6 Weeks
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score
Suicidility was defined as participants with major depressive disorder who experienced worsening of their depression and/or the emergence of suicidal ideation and behavior. Number of partcipants who experienced suicidality were reported. On the Suicidal Ideation scale of the Columbia Suicide-Severity Rating Scale (C-SSRS) participants were scored as "non-suicidal" (00), "wish to be dead" (01), "non-specific active suicidal thoughts" (02), "active suicidal ideation with associated thoughts of methods without intent" (03), "active suicidal ideation with some intent to act on suicidal thoughts without clear plan" (04) and "active suicidal ideation with plan and intent" (05), based on the most severe score (5 being the most severe).Suicidal ideation of type 4 or 5 in the C-SSRS was categorized as suicidility here.
Measured: Upto Week 6
Number of Participants With Abnormal Haematology and Clinical Chemistry Values
Samples for haematology and clinical chemistry were collected on Weeks 1, 5 and 6. The analyzed haematological parameters were platelet count, red blood cells count, white blood cells count, reticulocyte count, hemoglobin and hematocrit. The analyzed clinical chemistry parameters were urea, creatinine, glucose (fasting), sodium, lactate dehydrogenase (LDH), potassium, chloride, calcium, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, creatine kinase (CK), total and direct bilirubin, albumin, total protein and total cholesterol. Number of participants with any abnormal haematological or clinical chemistry parametrs are summarized here.
Measured: Upto Week 6
Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate)
Vital signs including systolic and diastolic blood pressure and heart rate were taken from day 1 upto follow-up visit. Number of participants with abnormal systolic blood pressure, diastolic blood pressure and heart rate values were summarized.
Measured: Up to follow-up Visit (Day 53)
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
ECG was obtained at Week 2 and Week 6. ECG was recorded using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and Corrected QT (QTc) intervals (Bazett's correction was applied to QTc measurements). Number of participants with abnormal ECG readings are summarized.
Measured: 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
Interlukin-6 (IL-6) and Tumor Necrosis Factor-Alpha (TNF-alpha) from the participants with Major Depressive Disorder (MDD) were evaluated and analyzed using suitable mixed-effects model repeated measures (MMRM). Exploratory analysis on plasma levels of IL-6 and TNF-alpha were performed. Week 0 values were considered as Baseline.The change from Baseline was calculated by subtracting the baseline values from the individual post-randomisation values.
Measured: Upto Week 6
Change From Randomisation Bech Total Score: Bech Score
HAMD-17 has 17 questions. 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 scale was extracted from the HAMD-17 and comprised of 6 items out of which 5 were 5 point questions and 1 was 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. Due to the small number of items, missing data was not imputed for the Bech Total Score. If any of the 6 items were missing, the total score was not calculated at that visit. The change from randomization was analysed using suitable Bayesian Mixed-Effects Models for Repeated Measures (BMMRM) assuming missing at random MAR.
Measured: Up to Follow-up visit (Day 53)
Mean HAMD-17 Total Score
HAMD-17 is Hamilton Depression Rating Scale which 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. If not more than 1 response was missing, the total score was caculated as Observed Total Score * [1 + (Sum of the Maximum Score of the missing values/Sum of the Maximum Score of the non -missing values)]. There were 9 five point questions and 8 three point questions. The responses to the individual questions can have values of 0-2 (three points response) or 0-4 (five points response).
Measured: Up to Follow-up visit (Day 53)
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score
The 30 item IDS is available in two versions IDS-C and Inventory of Depressive Symptomatology self-rated (IDS-SR). To calculate the total score of IDS, 28 out of the 30 items were scored. Either weight loss or weight gain, appetite loss or appetite gain is scored because only one member of each pair is applicable to any given respondent. The standard total score is obtained by summing the ratings of 28 of the 30 items. Each of the 28 items is scored on a 0 to 3 scale (0 - the absence of pathology; 3 - severe pathology). The total scores range from 0 to 84. If more than one response was missing then the score was calculated using the formula Observed Total Score*[1+(Sum of the Maximum Score of the missing values/Sum of the Maximum Score of the non -missing values)].
Measured: Up to Follow-up visit (Day 53)
Mean IDS-SR Total Score
The 30 item IDS is available in two versions IDS-SR and IDS-C. To calculate the total score of IDS, 28 out of the 30 items were scored. Either weight loss or weight gain, appetite loss or appetite gain is scored because only one member of each pair is applicable to any given respondent. The standard total score is obtained by summing the ratings of 28 of the 30 items. Each of the 28 items is scored on a 0 to 3 scale (0 - the absence of pathology; 3 - severe pathology). The total scores range from 0 to 84. If more than one response was missing then the score was calculated using the formula Observed Total Score*[1+(Sum of the Maximum Score of the missing values/Sum of the Maximum Score of the non -missing values)].
Measured: 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)
QIDS-SR assesses symptoms severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criterion for major depressive disorder. It contains 16 separate items (corresponding to 16 items of the much longer IDS-SR), defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain. The QIDS-SR total score was calculated by summing over the domain scores. The highest possible score was 27, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score.
Measured: 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).
The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. A responder is a participant who has a ≥50% reduction from randomisation in the total score for IDS-C. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%. The change from randomization was analysed using suitable Bayesian mixed-effects model repeated measures (BMMRM) assuming missing at random (MAR).
Measured: Week 6
Percentage of IDS-C Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. IDS-C total score was calculated for each participant at each timepoint and those participants with non-missing values for IDS-C total scores were categorised as having an IDS-C for the respective endpoint of ≤ 15 or > 15. Participants whose total score was ≤ 15 were included here.
Measured: Week 6
Percentage of IDS-SR Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. A responder is a participant who has a ≥50% reduction from randomisation in the total score for IDS-SR. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%. The change from randomization was analysed using suitable BMMRM assuming missing at random.
Measured: Week 6
Percentage of IDS-SR Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
The 30 item IDS is available in two versions IDS-C and IDS-SR. To calculate the total score of IDS, 28 out of the 30 items were scored. Either item 11 or 12 (and 13 or 14) were scored. If 11 and 12 (or 13 and 14) both are scored then the item with the highest score was considered. The total score of the 28 items ranged between 0-84. IDS-SR total score was calculated for each participant at each timepoint and those participants with non-missing values for IDS-SR total scores were categorised as having an IDS-C for the respective endpoint of ≤ 15 or > 15. Participants whose total score was ≤ 15 were included here.
Measured: Week 6
Percentage of QIDS-SR16 Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
QIDS-SR assesses symptoms severity of DSM-IV diagnostic criterion for major depressive disorder. It contains 16 separate items (corresponding to 16 items of the much longer IDS-SR), defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain.The highest possible score was 27, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score. A responder is a participant who has a ≥50% reduction from randomisation in the total score for that given endpoint. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%.
Measured: Week 6
Percentage of QIDS-SR16 Remitters (Subjects Whose Total Score Was ≤ 5 at Week 6/Study Exit).
QIDS-SR assesses symptoms severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criterion for major depressive disorder. It contains 16 separate items (corresponding to 16 items of the much longer IDS-SR), defining 9 DSM-IV symptom criterion domains. A total score was obtained by summing scores on each domain. The QIDS-SR total score was calculated by summing over the domain scores. The highest possible score was 27, which represented the most severe measure of depression; the lowest possible score was 0, which represented an absence of depression. Due to the small number of items, missing data was not imputed for the QIDS-SR total score. The QIDS total score was calculated for each subject at each timepoint and those subjects with no missing value for QIDS total score was categorised as having a QIDS total score of ≤ 5 or > 5. Participants whose total score was ≤ 5 were included here.
Measured: Week 6
Percentage of Bech Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
The Bech scale was extracted from the HAMD-17 and comprised of 6 items out of which 5 were 5 point questions and 1 was 3 point question. The Bech Total Score was calculated by summing the individual response scores. Due to the small number of items, missing data was not imputed for the Bech Total Score. If any of the 6 items were missing, the total score was not calculated at that visit. A responder is a participant who has a ≥50% reduction from randomisation in the total score for that given endpoint. The total score was calculated for each participant at each timepoint and the percentage change from randomisation was then calculated as ([Total score at post randomisation visit - Total score at randomisation visit]/ Total score at randomisation visit) * 100%. Responders were those with values of ≤ -50%. The change from randomization was analysed using suitable BMMRM assuming missing at random.
Measured: Week 6
Percentage of Bech Remitters (Participants Whose Total Score Was ≤ 4 at Week 6/Study Exit).
The Bech scale was extracted from the HAMD-17 and comprised of 6 items out of which 5 were 5 point questions and 1 was 3 point question. The Bech Total Score was calculated by summing the individual response scores. Due to the small number of items, missing data was not imputed for the Bech Total Score. If any of the 6 items were missing, the total score was not calculated at that visit. The change from randomization was analysed using suitable BMMRM assuming missing at random MAR. The BECH total score was calculated for each subject at each timepoint and those perticipants with no missing value for BECH total score were categorised as having a BECH total score of ≤ 4 or > 4.
Measured: 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.
The number of participantts with a CGI-I score of either 1 ("very much improved") or 2 (much improved") were grouped together for each timepoint. Participants with no missing CGI-I scores were categorised as having a CGI-I score of ≤ 2 or > 2.
Measured: Weeks 1, 2, 3, 4, 5 and 6
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks
CGI-S assesses the severity of the participant's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill). The number of participants with a CGI-I score of either 1 ("very much improved") or 2 (much improved") were grouped together for each timepoint. Participants with no missing CGI-S scores were categorised as having a CGI-S score of ≤ 2 or > 2. The total score was calculated for each participant at each timepoint and percentage was calculated.
Measured: Upto Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2009 (estimated)
- Study start25 Sep 2009
- Primary completion7 Jul 2010
- Study completion7 Jul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00976560
- Sponsor's protocol ID
- 113009
- Acronym
- PKI113009
- Status last verified
- Oct 2017
- First submitted
- 11 Sep 2009
- Last updated
- 14 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00976560
- Acronym / sponsor ID
- PKI113009 / 113009
- Conditions
- Depressive Disorder, Major
- Keywords
- Lack of interest and energy, Psychomotor retardation, Cytokines, Major Depressive disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2009 (actual)
- Primary completion
- 7 Jul 2010 (actual)
- Study completion
- 7 Jul 2010 (actual)
- First posted
- 14 Sep 2009 (estimated)
- Results
- Posted 14 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GW856553 | Experimental | Drug: GW856553GW856553 7.5 mg BID |
| Placebo | Placebo comparator | Other: PlaceboMatching Placebo BID |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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 (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GW856553Wet Granulated, film coated white, 9mm round, biconvex, plain faced tablets, containing 7.5 mg of GW856553 | Drug | GW856553 |
| PlaceboFilm coated white, 9mm round, biconvex, plain faced tablets obtained by direct compression. | Other | Placebo |
Primary outcome
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.
Time frame: 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).
21 secondary outcomes
Number of Participants With Adverse Events
Time frame: 6 Weeks
Number of Participants With Suicidality as Assessed by the Columbia Suicidality Severity Rating Scale Score
Time frame: Upto Week 6
Number of Participants With Abnormal Haematology and Clinical Chemistry Values
Time frame: Upto Week 6
Number of Participants With Abnormal Vital Signs (Blood Pressure, Heart Rate)
Time frame: Up to follow-up Visit (Day 53)
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: 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
Time frame: Upto Week 6
Change From Randomisation Bech Total Score: Bech Score
Time frame: Up to Follow-up visit (Day 53)
Mean HAMD-17 Total Score
Time frame: Up to Follow-up visit (Day 53)
Mean Inventory of Depressive Symptomatology Clinician (IDS-C) Total Score
Time frame: Up to Follow-up visit (Day 53)
Mean IDS-SR Total Score
Time frame: 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)
Time frame: 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).
Time frame: Week 6
Percentage of IDS-C Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
Time frame: Week 6
Percentage of IDS-SR Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
Time frame: Week 6
Percentage of IDS-SR Remitters (Participants Whose Total Score Was ≤ 15 at Week 6/Study Exit).
Time frame: Week 6
Percentage of QIDS-SR16 Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
Time frame: Week 6
Percentage of QIDS-SR16 Remitters (Subjects Whose Total Score Was ≤ 5 at Week 6/Study Exit).
Time frame: Week 6
Percentage of Bech Responders (Participants With a Reduction in Total Score of ≥ 50% From Randomization at Week 6/Study Exit).
Time frame: Week 6
Percentage of Bech Remitters (Participants Whose Total Score Was ≤ 4 at Week 6/Study Exit).
Time frame: 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.
Time frame: Weeks 1, 2, 3, 4, 5 and 6
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) up to 6 Weeks
Time frame: Upto Week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
21 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GW856553 in people with Depressive Disorder, Major, run by GlaxoSmithKline at 21 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Germany, Russia, United States, Bulgaria, Estonia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: At Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2017.