A Study of GW856553X For the Treatment of Depression

NCT00569062 | Terminated Phase 2

• 1 other identifier: PKI108574
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 15

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.

Conditions

Depressive Disorder, Major

Keywords

Psychomotor retardation; cytokines; GW856553; Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (4)

• Change from Randomization at Week 6 in Bech subscale (6-item of 17-item Hamilton depression rating [HAMD-17] scale) score

  HAMD is an instrument for evaluating severity of symptoms of depression, was completed by the participant. The instrument used in this study was the 17-item version (HAM-D17). The Bech subscale of the HAMD-17 is composed of 6 identified items out of the 17 items rated in HAMD-17 scale. Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4). The following symptoms were rated on a 5-point scale (0-4): depressed mood, low self-esteem (guilt), work and interests, psychomotor retardation, and anxiety (psychic). The following symptom was rated on a 3-point scale (0-2): somatic symptoms (general). Total score ranged from 0 to 22, with 0 indicating absence of symptoms and a higher score indicating greater severity of symptoms. Randomization value was defined as the assessment done on Day 1 (Week 0). Change from Randomization was calculated by subtracting the Randomization value from the post-Randomization (Week 6) value.

  Day 1 (Randomization, Week 0) and Week 6

• Change from Randomization (Week 0) at Week 6 in Inventory for Depressive Symptomatology-Clinician rated (IDS-C) scale total score

  The IDS-C is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. In order to calculate the total score of IDS-C, the following procedures were used: either item 11 or 12 were scored; either item 13 or 14 were scored; if both items 11 and 12 (or 13 and 14) were scored, the highest of the items was scored. The total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Randomization value was defined as the assessment done on Day 1 (Week 0). Change from Randomization was calculated by subtracting the Randomization value from the post-Randomization (Week 6) value.

  Day 1 (Randomization, Week 0) and Week 6

• Change from randomization (Week 0) at Week 6 in Quick Inventory of Depressive symptomatology 16 item self report (QIDS-SR16) scale total score

  The QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by the participant. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. The total score was obtained by adding the scores of the items of depressed mood, decreased interest, fatigue, guilt, concentration, suicidal ideation, the highest score on any 1 of the 4 sleep items, the highest score on any 1 appetite/weight item and the highest score on either of the 2 psychomotor items. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating the most severe depression. Randomization value was defined as the assessment done on Day 1 (Week 0). Change from Randomization was calculated by subtracting the Randomization value from the post-Randomization (Week 6) value.

  Day 1 (Randomization, Week 0) and Week 6

• Change from Randomization (Week 0) at Week 6 in the morning serum levels of the pro-inflammatory biomarkers

  The pro-inflammatory biomarkers include the cytokines interleukin 6 (IL-6), IL-10, interleukin 2 receptor alpha (IL-2ra) and tumour necrosis factor alpha (TNFα). Increased circulating levels of IL-6 and TNFα were consistently described in populations of participants suffering from MDD during the symptomatic episode. The assessments were done at Week 0, Week 2 and Week 6. Serum samples for the assessment were taken at 8:00-9:00 h (before dosing and safety blood/urine sampling), 10:00-11:00 h and 12:00-13:00 h (+/-30 minutes). Randomization value was defined as the assessment done on Day 1 (Week 0, pre-dose). Change from Randomization was calculated by subtracting the Randomization value from the post-Randomization (Week 6) value.

  Day 1 (Randomization, Week 0) and Week 6

Secondary Outcomes (30)

• Number of participants with any Adverse events (AEs), Serious adverse events (SAEs) or Death

  Up to Follow-up (Up to 53 days)

• Mean Suicidality Tracking Scale (STS) scores over period

  Week 0 up to Week 6

• Number of participants with abnormal chemistry values

  Up to Follow-up (Up to 53 days)

• Number of participants with abnormal hematology values

  Up to Follow-up (Up to 53 days)

• Number of participants with abnormal urinalysis results

  Up to Follow-up (Up to 53 days)

Study Arms (2)

Arm 1

EXPERIMENTAL

GW856553X 7.5mg BID for 6 weeks

Drug: GW856553X

Placebo

PLACEBO COMPARATOR

Placebo to match, BID, 6 weeks

Other: Placebo

Interventions

GW856553X DRUG

GW856553X 7.5mg BID for 6 weeks

Arm 1

Placebo OTHER

Placebo to match GW856553X

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Tartu, 50417, Estonia

Location

GSK Investigational Site

Bangalore, 560029, India

Location

GSK Investigational Site

Bangalore, 560034, India

Location

GSK Investigational Site

Ludhiana, 141001, India

Location

GSK Investigational Site

Manipal, 576 104, India

Location

GSK Investigational Site

Mumbai, 400010, India

Location

GSK Investigational Site

Pune, 411004, India

Location

GSK Investigational Site

Moscow, 107076, Russia

Location

GSK Investigational Site

Moscow, 115522, Russia

Location

GSK Investigational Site

Moscow, 119992, Russia

Location

GSK Investigational Site

Moscow, 123367, Russia

Location

GSK Investigational Site

Nizhny Novgorod, 603115, Russia

Location

GSK Investigational Site

Saint Petersburg, 193167, Russia

Location

GSK Investigational Site

Saint Petersburg, Russia

Location

GSK Investigational Site

Smolensk, 214 019, Russia

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Depressive Disorder, Major; Psychomotor Disorders

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2007
• First Posted: December 6, 2007
• Study Start: September 12, 2007
• Primary Completion: June 25, 2008
• Study Completion: June 25, 2008
• Last Updated: July 18, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

IN (6); ES (1); RU (8)