Clinical trial NCT00569062: A Study of GW856553X For the Treatment of Depression
Official title: A Randomized, Double Blind, Placebo Controlled Study to Explore the Antidepressant Properties of P38a Kinase Inhibitor GW856553X 15mg Compared to PBO in Subjects With Major Depressive Disorder Exhibiting Symptoms of Loss of Energy and Interest and Psychomotor Retardation, for a Six Week Treatment Period
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Depressive Disorder, Major
Keywords: Psychomotor retardation
cytokines
GW856553
Major Depressive Disorder (MDD)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-12-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: GW856553 is a novel compound, currently in development for the treatment of Major Depressive Disorder (MDD), and other indications. GW856553 inhibits a protein which is responsible for the production of some pro-inflammatory molecules, called cytokines. Increased blood levels of these molecules were seen in populations of MDD patients and this was more apparent in subjects with severe symptoms, psychomotor retardation and loss of energy. Aim of the present study is to assess whether GW856553, by inactivating this protein, is able to suppress the production of the cytokines, and ultimately relieving depression symptoms. In this study GW856553 or placebo is given to MDD patients 7.5md twice daily for 6 weeks.

Detailed description: A randomised, double-blind, placebo-controlled study to explore the antidepressant properties of the P38a kinase inhibitor GW856553X 15mg compared to placebo in subjects with Major Depressive Disorder exhibiting symptoms of loss of energy and interest, and psychomotor retardation, for a six week treatment period.

Eligibility criteria: Inclusion Criteria:

* Male or female = 18 years of age and \< 60 years,
* routine laboratory results within normal ranges,
* Body Mass Index within the range 18.5-35.0 kg/m2 inclusive.
* Subject must have had at least one previous major depressive episode with a diagnosis of MDD in his/her history, and had a successful pharmacological treatment of that episode, and is currently experiencing a recurrence of MDD presently un-medicated.
* Subjects must met the diagnosis of an episode of Major Depressive Disorder in the past 12 weeks but not greater than 24 months.

Exclusion Criteria:

* The subject has any history of liver disease.
* The subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that, in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial.
* The subject has a history of autoimmune diseases.
* The subject has any active infectious diseases, including active tuberculosis or a history of active tuberculosis.
* The subject has a history of malignancy, except for surgically cured basal cell carcinoma or females with cured cervical carcinoma (\> 2 yrs prior).
* The subject has a history of HIV or other immunosuppressive disease.
* The subject has uncontrolled diabetes.
* The subject is pregnant or nursing.
* Subject has no contact with an adult on a daily basis (i.e., subjects who are not living with at least one other adult or subjects who do not have an adult who contacts them on a daily basis).
* Subject has initiated psychotherapy within three months prior to the Screening visit, or plans to initiate psychotherapy during the trial.
* Subject has received electroconvulsive therapy or transcranial magnetic stimulation or vagal nerve stimulation within the six months prior to the Screening.
* The subject is currently receiving a chronic biological or pharmacologic anti-inflammatory therapy; interferon therapy at any dose or did receive them within 6 months prior randomisation.
* Subjects who have donated a unit of blood within the previous month or intends to donate in the month after completing the study

Primary outcomes:
measure: Change from Randomization at Week 6 in Bech subscale (6-item of 17-item Hamilton depression rating [HAMD-17] scale) score
timeFrame: Day 1 (Randomization, Week 0) and Week 6
measure: Change from Randomization (Week 0) at Week 6 in Inventory for Depressive Symptomatology-Clinician rated (IDS-C) scale total score
timeFrame: Day 1 (Randomization, Week 0) and Week 6
measure: Change from randomization (Week 0) at Week 6 in Quick Inventory of Depressive symptomatology 16 item self report (QIDS-SR16) scale total score
timeFrame: Day 1 (Randomization, Week 0) and Week 6
measure: Change from Randomization (Week 0) at Week 6 in the morning serum levels of the pro-inflammatory biomarkers
timeFrame: Day 1 (Randomization, Week 0) and Week 6
Secondary outcomes:
measure: Number of participants with any Adverse events (AEs), Serious adverse events (SAEs) or Death
timeFrame: Up to Follow-up (Up to 53 days)
measure: Mean Suicidality Tracking Scale (STS) scores over period
timeFrame: Week 0 up to Week 6
measure: Number of participants with abnormal chemistry values
timeFrame: Up to Follow-up (Up to 53 days)
measure: Number of participants with abnormal hematology values
timeFrame: Up to Follow-up (Up to 53 days)
measure: Number of participants with abnormal urinalysis results
timeFrame: Up to Follow-up (Up to 53 days)
measure: Number of participants of vital signs outside range of Potential Clinical Importance (PCI)
timeFrame: Up to Follow-up (Up to 53 days)
measure: Number of participants of abnormal electrocardiogram (ECG) values
timeFrame: Up to Follow-up (Up to 53 days)
measure: Change from randomization (Week 0) at Week 1, 2, 3, 4 and 5 in Bech subscale (6-item of HAMD-17 scale) score
timeFrame: Day 1 (Randomization, Week 0) up to Week 5
measure: Change from Randomization (Week 0) at Week 1, 2, 3, 4 and 5 in IDS-C scale total score
timeFrame: Day 1 (Randomization, Week 0) up to Week 5
measure: Change from randomization (Week 0) at Week 2 and 4 in QIDS-SR16 scale total score
timeFrame: Day 1 (Randomization, Week 0) up to Week 4
measure: Change from randomization (Week 0) at Week 1, 2, 3, 4, 5 and 6 in HAMD-17 scale total score
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Percentage of participants with Bech subscale (6-item HAMD-17) score responder and remitter at Week 6
timeFrame: Week 6
measure: Percentage of participants with IDS-C scale total score responder and remitter at Week 6
timeFrame: Week 6
measure: Percentage of participants with QIDS-SR16 scale total score responder and remitter at Week 6
timeFrame: Week 6
measure: Change from Randomization in Psychomotor Retardation subscale of the IDS-C scale over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in Psychomotor Retardation subscale of the QIDS-SR16 scale over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in Psychomotor Retardation-Psychomotor Slowing item 23 of the IDS-C scale over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in Psychomotor Retardation-Psychomotor Slowing item 15 of QIDS-SR16 scale over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Functional assessment of Fatigue and Sleepiness over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in Visual Analogue Scale (VAS) of Fatigue/Tiredness and Sleepiness (at time of cytokine sampling) over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in Fatigue-Energy item 20 of the IDS-C scale over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in Energy/Fatigue item 14 of the QIDS-SR16 scale over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in plasma cortisol over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in serum TNFα/IL-10 ratio over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in high sensitivity C-reactive protein (hs-CRP) over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Change from Randomization in number of leukocytes over Week 6
timeFrame: Day 1 (Randomization, Week 0) up to Week 6
measure: Plasma concentration of GW856553X and GSK198602
timeFrame: Pre-dose and 4 h post-dose at Week 2 and Week 6
measure: Maximum plasma concentration (Cmax) of GW856553X and GSK198602
timeFrame: Pre-dose and 4 h post-dose at Week 2 and Week 6
measure: Median time to Cmax (tmax) and the terminal phase half-life (t1/2)
timeFrame: Pre-dose and 4 h post-dose at Week 2 and Week 6
measure: The area under the plasma concentration-time curve (AUC)
timeFrame: Pre-dose and 4 h post-dose at Week 2 and Week 6
Other outcomes:
Locations:
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Bangalore
country: India
facility: GSK Investigational Site
city: Bangalore
country: India
facility: GSK Investigational Site
city: Ludhiana
country: India
facility: GSK Investigational Site
city: Manipal,
country: India
facility: GSK Investigational Site
city: Mumbai
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Nizhny Novgorod
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
city: St.Petersburg
country: Russian Federation
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: