A Repeat Dose Study in Healthy Volunteers Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK356278

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01573819
• Date of registration: 16/02/2012
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: A Repeat Dose Study in Healthy Volunteers Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK356278
• Scientific title: A Randomised, Placebo Controlled, Ascending, Repeat Dose Study in Healthy Volunteers Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK356278
• Date of first enrolment: November 24, 2011
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01573819
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: Single (Participant).
• Phase: Phase 1

Countries of recruitment

Netherlands

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

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 medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring. A subject with a clinically significant abnormality or laboratory
parameters significantly outside the reference range for the population being studied
may be included only if the Investigator and the GSK Medical Monitor agree that the
finding is unlikely to introduce additional risk factors and will not interfere with
the study procedures.

- Male or female between 18 and 65 years of age inclusive, at the time of signing the
informed consent.

- A female subject is eligible to participate if she is of: Non-childbearing potential
is defined as pre-menopausal females with a documented tubal ligation or hysterectomy;
or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable
cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than
40 MlU/ml and estradiol less than 40 pg/ml (less than 147 pmol/L) is confirmatory.
Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt
will not be eligible for the study.

- Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods listed in the protocol (contraception requirements). This
criterion must be followed from the time of the first dose of study medication until
the follow up visit.

- Body weight greater than and equal to 50 kg and BMI within the range 19 - 30 kg/m2
(inclusive).

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.Average of triplicate QTcF
less than 450 msec (on an average of triplicate values)

- Normal echocardiography, plasma troponin and BNP levels confirmed before first dose

Exclusion Criteria:

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- Chronic history of liver disease, or known hepatic or biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones).

- A positive pre-study drug/alcohol screen.

- A positive test for HIV antibody.

- History of regular alcohol consumption within 6 months of the study defined as: An
average weekly intake of greater than 21 units for males or greater than 14 units for
females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 ml)
of beer, 1 glass (125ml) of wine or 1 (25 ml) measure of spirits.

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
subject safety.

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 30 day period.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco or
nicotine-containing products within 6 months prior to screening.

- Unable to refrain from consumption of red wine, seville oranges, grapefruit or
grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids from 7
daysprior to the first dose of study medication.

- Any history of suicidal behaviours or any suicidal ideation of type 4 or 5 on the CSSR
in the last six months.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Huntington Disease

Intervention(s)

Drug: Placebo

Drug: GSK356278

Primary Outcome(s)

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

Safety and tolerability parameters including change from baseline for telemetry ECGs [Time Frame: 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 Columbia Suicide Severity Rating Scale (C-SSRS) [Time Frame: 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 [Time Frame: 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 for clinical laboratory tests [Time Frame: 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]

Safety and tolerability parameters including change from baseline in the collection of adverse events [Time Frame: 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]

Composite (or Profile) of Pharmacokinetics [Time Frame: 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.]

Safety and tolerability parameters including change from baseline for echocardiography [Time Frame: 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 12-lead ECGs [Time Frame: 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 Bond and Lader VAS [Time Frame: 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 measures for vital signs [Time Frame: 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.]

Secondary Outcome(s)

Pharmacodynamic parameters including change from baseline for electroencephalography [Time Frame: Cohort 2 for 13 days Cohort 3 repeat dose for 25 days]

Pharmacodynamic parameters including change from baseline for cognition test [Time Frame: Cohort 2 for 12 days Cohort 3 repeat dose for 26 days]

Pharmacodynamic parameters including change from baseline for plasma Brain-derived neurotrophic factor [Time Frame: 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]

Secondary ID(s)

115719

Source(s) of Monetary Support

Please refer to primary and secondary sponsors