GSK239512 DDI Study

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01802931
• Date of registration: 04/01/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: GSK239512 DDI Study
• Scientific title: An Open Label Study in Healthy Volunteers to Investigate the Effect of Ketoconazole on the Pharmacokinetics of GSK239512
• Date of first enrolment: January 7, 2013
• Target sample size: 22
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01802931
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male between 18 and 45 years of age inclusive, at the time of signing the informed
consent.

2. 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 clinical abnormality or laboratory parameters
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.

3. ALT, alkaline phosphatase and bilirubin < or = 1.5xULN (isolated bilirubin >1.5xULN is
acceptable if bilirubin is fractionated and direct bilirubin <35%).

4. QTcF < 450 msec.

5. Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods listed in the protocol. This criterion must be followed from
the time of the first dose of study medication until 1 month post-last dose of
GSK239512.

6. Body weight > 50 kg, and body mass index (BMI) between 19.0 - 29.9 kg/m2 inclusive.

7. Capable of giving informed consent and can comply with the study requirements and
timetable.

Exclusion Criteria:

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

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

3. A positive pre-study drug/alcohol screen.

4. A positive test for Human Immunodeficiency Virus (HIV) antibody.

5. History of alcohol consumption exceeding, on average, 21 drinks/week for men (1 drink
= 100 mL of wine or 240 mL of beer or 30 mL of hard liquor in Australia) within 6
months of the first dose of study medication.

6. History of smoking cigarettes or using tobacco products or any nicotine-containing
products (including nicotine patches) within 3 months of screening.

7. The subject has participated in a clinical trial and has received an investigational
product within 30 days or 5 half lives (whichever is longer) prior to the first dosing
day in the current study.

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

9. Unable to refrain from the 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.

10. History of sensitivity to ketoconazole, or to the excipients contained in GSK239512 or
Nizoral, or a history of drug or other allergy that, in the opinion of the
investigator or GSK Medical Monitor, contraindicates their participation.

11. Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

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

13. Subject is mentally or legally incapacitated.

14. Have used the following medications within the last 30 days or 5 half-lives (whichever
is longer) prior to screening and are not able to discontinue use throughout
participation in the clinical trial:

- Any CNS stimulants (e.g., modafinil, dexamphetamine, methylphenidate).

- Known potent P-glycoprotein inhibitors (e.g. itraconazole, ketoconazole,
cyclosporin, loperamide, diltiazem, verapamil, spironolactone, quinidine,
bepridil, quinine, carvedilol).

- Known potent inhibitors or inducers of the CYP3A4 enzyme (see Appendix 3).

- CNS-penetrant antihistamines (e.g. bromopheniramine, chlorpheniramine,
clemastine, diphenhydramine, hyrdoxyzine)

- Any other medicines that are contraindications of Nizoral (see Appendix 4).

15. Unable to refrain from consumption of red wine, seville oranges, grapefruit or
grapefruit juice from 7 days prior to the first dose of study medication.

16. The subject has a history of significant psychiatric illness.

17. Presence or history of hallucinations that, in the judgement of the investigator, may
increase the safety risk to the subject.

18. At risk of suicide, as indicated by:

- A documented history of attempted suicide or significant suicidal ideation during
the 6 months preceding the screening visit, OR

- If in the investigator's judgment the subject is at risk of a suicide attempt
based on the screen visit assessment, including the C-SSRS.

19. Diagnosis of any type epilepsy

20. Night shift workers within 4 weeks of first dosing

21. Presence of significant and routine sleep disturbance that has a negative impact on
quality of life that, in the judgement of the investigator, may increase the risk of
tolerability issues during dose escalation.

- Examples of significant sleep disturbances may be: severe insomnia, nocturnal
wandering, confusion, disorientation, agitation, or vivid dreams.



Age minimum: 18 Years
Age maximum: 45 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: GSK239512

Drug: ketoconazole

Primary Outcome(s)

Cmax of GSK239512 [Time Frame: Predose and up to 120 hour post dose of GSK239512]

AUC of GSK239512 [Time Frame: Predose and up to 120 hour post dose of GSK239512]

Secondary Outcome(s)

Number of participants with adverse events as a measure of safety and tolerability [Time Frame: 15 weeks]

Secondary ID(s)

117016

Source(s) of Monetary Support

Please refer to primary and secondary sponsors