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GSK372475

Phase 2

Depressive Disorder | Small molecule | Other |GSK plc|Last Updated: Feb 5, 2018

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDBiomarker
Total Trials3
Total Enrollment954
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00448058A Study Of New Medicine (GSK 372475) For The Treatment Of DepressionPHASE2 COMPLETED 396Apr 1, 2007Dec 1, 2008Oct 10, 201442 Australia, Belgium +10
NCT00420641MDD POC Study GSK372475 Subjects Depressive DiseasePHASE2 COMPLETED 492Dec 19, 2006Oct 15, 2008Feb 5, 201833 Bulgaria, Canada +8
NCT00728208GSK372475 PK Study in Healthy VolunteersPHASE1 COMPLETED 66Jul 28, 2008Dec 29, 2008Jul 13, 20171 Germany
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Study Endpoints
Primary Endpoints
Change from randomization to the end of the Treatment Phase (Week 10) on a depression rating scale.
Randomisation (week 0) And end of the treatment
Mean Change From Randomization at the End of the Treatment Phase in the MADRS Total Score
Week 0 (Randomization) and Week 10

The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score is 60; 0, no depression; 60, severely depressed. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS total score at the time point being analyzed (Week 10) to Randomization.

Change From Randomization at the End of the Treatment Phase (Week 10) in Bech Scale (6-item of 17-item Hamilton Depression Rating [HAMD-17] Scale) Score
Week 0 (Randomization) and Week 10

The HAMD is a rating instrument for evaluating severity of symptoms of depression, was completed by the participant. The rating instrument used in this study was the 17-item version (HAM-D17). The Bech scale 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, feeling of 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 value done on Week 0. Change from Randomization in total score was the difference between Bech total score at the time point being analyzed (Week 10) to Randomization.

Mean Change From Randomization at the End of the Treatment Phase (Week 10) in Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Total Score
Week 0 (Randomization) and Week 10

The IDS-CR 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-CR, 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 value done on Week 0. Change from Randomization in total score was the difference between IDS-CR total score at the time point being analyzed (Week 10) to Randomization.

Main pharmacokinetic parameters after single and repeat administration: Cmax, tmax, AUC(0-t), AUC(0-tau), Ctau and Ro.
pre-dose to 24 hours post dose
Secondary Endpoints
Endpoints related to response & remission on depression rating scales during time of treatment exposureChange during treatment & at endpoint-week 10:in Clinical Global Impression scale; in motivation, energy, & sexual functioning on patient-rated scales
Randomisation (week 0) and at weeks 1,2,4,6,8 and week 10 (end of treatment phase)
Mean Change From Randomization in IDS- Self-Rated Version (SR) Total Score Over Week 10
Week 0 (Randomization) up to Week 10
Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10
Week 0 (Randomization) up to Week 10
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Study Design & Arms
AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
GSK372475EXPERIMENTALflexible-dose design from GSK372475 1.0 mg/day to GSK372475 2.0 mg/day
VenlafaxineACTIVE_COMPARATORFlexible- dose design from Venlafaxine XR 75 mg/day to Venlafaxine XR 225 mg/day
placeboPLACEBO_COMPARATOR -
GSK372475 ArmEXPERIMENTALGSK372475 1.0- 1.5 mg/day
Paroxetine ArmEXPERIMENTALParoxetine 20-30 mg/day
Interventions
NameTypeDescription
GSK372475DRUGdaily administration during the 10-week treatment phase
venlafaxineDRUGdaily administration during the 10-week treatment phase
placeboDRUGdaily administration during the 10-week treatment phase
ParoxetineDRUGParoxetine 20-30 mg/day
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Eligibility Criteria
Age Range18 Years — 64 Years
SexALL
Healthy VolunteersNo
Study Sites42

Inclusion Criteria: * Major depressive episode (MDE) associated with Major Depressive Disorder (DSM-IV-TR criteria) * Duration of current episode is at least 12 weeks duration and less than 2 years * Symptoms of decreased energy, pleasure, and interest * Female subjects who agree to use acceptable ...

Countries:AustraliaBelgiumBulgariaCanadaEstoniaFinlandFranceGermanyIndiaPolandSlovakiaSouth AfricaChileCosta RicaCroatiaItaly
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