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GSK356278

Phase 1

Huntington Disease | Small molecule | Rare Disease |GSK plc|Last Updated: Jun 20, 2017

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
RandomizedCONTROLLEDBiomarker
Total Trials2
Total Enrollment44
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01573819A Repeat Dose Study in Healthy Volunteers Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK356278PHASE1 COMPLETED 36 — — Nov 24, 2011Apr 2, 2012Jun 15, 20171 Netherlands
NCT01602900Healthy Volunteer Positron Emission Tomography (PET) Brain Occupancy Study of a Phosphodiesterase 4 (PDE4) Inhibitor in Huntington's DiseasePHASE1 COMPLETED 8 — — Nov 22, 2011Apr 12, 2012Jun 20, 20172 United Kingdom
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Study Endpoints
Primary Endpoints
Composite (or Profile) of Pharmacokinetics
Cohort 1 for 288 hours post dose; Cohort 2 for 384 hours post dose; Cohort 3 single dose session for 72 hours; Cohort 3 repeat dose session for 744 hours post dose.

The primary pharmacokinetic endpoints following oral administration are: peak plasma concentration (Cmax), time of peak plasma concentration (tmax), area under the plasma concentration-time curve over the dose interval , and area under the plasma concentration-time curve from time-zero extrapolated to infinite time, accumulation ratio (Ro), terminal half-life (t½ ), apparent oral clearance (CL/F) and trough concentration.

Safety and tolerability parameters including change from baseline measures for vital signs
Cohort 1 for 15 days post dose; Cohort 2 for 19 days post dose; Cohort 3 single dose session for 4 days post dose; Cohort 3 repeat dose for 33 days post dose.
Safety and tolerability parameters including change from baseline for 12-lead ECGs
Cohort 1 for 15 days post dose; Cohort 2 for 19 days post dose; Cohort 3 single dose session for 4 days post dose; Cohort 3 repeat dose for 33 days post dose.
Safety and tolerability parameters including change from baseline for telemetry ECGs
Cohort 1 for 8 hours 30 minutes on Day 1 and Day 10; Cohort 2 for 8 hours 30 minutes on Day 1 and Day 14; Cohort 3 single dose session for 8 hours 30 minutes on Day 1; Cohort 3 repeat dose for 8 hours 30 minutes on Day 1 on Day28.
Safety and tolerability parameters including change from baseline for clinical laboratory tests
Cohort 1 for up to 28 days; Cohort 2 for up to 32 days; Cohort 3 single dose for 2 days; Cohort 3 repeat dose for up to 46 days

hematology, chemistry, liver function enzymes, troponin, B-type natriuretic peptide, inflammatory markers (Haptoglobin, fibrinogen, CRP, IL-6) and urinalysis

Safety and tolerability parameters including change from baseline for clinical lab tests
Cohort 1 for 11 days; Cohort 2 for 15 days; Cohort 3 single dose for 2 days; Cohort 3 repeat dose for 29 days

Inflammatory markers (Haptoglobin, fibrinogen, CRP, IL-6)

Safety and tolerability parameters including change from baseline for echocardiography
Cohort 1 for 12 days; Cohort 2 for 16 days; Cohort 3 repeat dose for 30 days
Safety and tolerability parameters including change from baseline for Bond and Lader VAS
Cohort 1 for 10 days; Cohort 2 for 14 days; Cohort 3 single dose for 2-3 hours post dose on Day 1; Cohort 3 repeat dose for 28 days
Safety and tolerability parameters including change from baseline for Columbia Suicide Severity Rating Scale (C-SSRS)
Cohort 1 for 14 days; Cohort 2 for 18 days; Cohort 3 repeat dose for 32 days
Safety and tolerability parameters including change from baseline for Rhodes Index of Nausea, Vomiting and Retching
Cohort 1 for 11 days; Cohort 2 for 15 days; Cohort 3 single dose for 2 days; Cohort 3 repeat dose for 28 days
Safety and tolerability parameters including change from baseline in the collection of adverse events
Cohort 1 for 14 days; Cohort 2 for up to 32 days; Cohort 3 single dose for 4 days; Cohort 3 repeat dose for up to 46 days
Positron Gamma-ray emmision & voxel counts
60 minutes

Brain regions of interest and associated radionuclitide-activity

systemic plasma concentration
24 hours

serial sampling: GSK356278 concentration expressed as mass per unit of volume

Secondary Endpoints
Pharmacodynamic parameters including change from baseline for electroencephalography
Cohort 2 for 13 days Cohort 3 repeat dose for 25 days
Pharmacodynamic parameters including change from baseline for cognition test
Cohort 2 for 12 days Cohort 3 repeat dose for 26 days
Pharmacodynamic parameters including change from baseline for plasma Brain-derived neurotrophic factor
Cohort 1 for 11 days; Cohort 2 for 15 days; Cohort 3 single dose session for 2 days; Cohort 3 repeat dose session for 29 days
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Study Design & Arms
AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeBASIC_SCIENCE
Treatment Arms
ArmTypeDescription
Cohort 1EXPERIMENTALA dose of 2mg per day for 10 days
Cohort 2EXPERIMENTALA dose of Xmg for 14 days. the dose will be determined from Cohort 1 not to exceed 14 mg
Cohort 3EXPERIMENTALa single dose of Ymg with a wash out of 7 days followed by 28 days of repeat dosing. The dose (Ymg) will be determined from cohort 1 and 2 not to exceed 14 mg.
GSK356278EXPERIMENTALInvestigational drug
Interventions
NameTypeDescription
GSK356278DRUGCohort 1: A dose of 2mg per day for 10 days; Cohort 2: A dose of Xmg for 14 days. the dose will be determined from Cohort 1 not to exceed 14 mg; Cohort 3: a single dose of Ymg with a wash out of 7 days followed by 28 days of repeat dosing. The dose (Ymg) will be determined from cohort 1 and 2 not to exceed 14 mg.
PlaceboDRUGCohort 1, a placebo per day for 10 days Cohort 2, a placebo per day for 14 days Cohort 3, a single placebo with a wash out of 7 days followed by 28 days of repeat dosing of a placebo per day.
RolipramDRUGChallenge Agent
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Eligibility Criteria
Age Range18 Years — 65 Years
SexALL
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * AST, ALT, alkaline phosphatase and bilirubin less than and equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%). * Healthy as determined by a responsible and experienced physician, based on a m...

Countries:NetherlandsUnited Kingdom
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Competitive Landscape -Huntington's Disease 9 trials
CompanyTickerTrialsLead PhaseDrugs
Novartis AG Sponsored ADRNVS2PHASE3Votoplam
Neurocrine Biosciences, Inc.NBIX2PHASE3Valbenazine
Alnylam Pharmaceuticals, IncALNY1PHASE1ALN-HTT02
uniQure N.V.QURE2PHASE1intra-striatal rAAV5-miHTT
Sarepta Therapeutics, Inc.SRPT1PHASE1SRP-1005
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