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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01802931




Registration number
NCT01802931
Ethics application status
Date submitted
4/01/2013
Date registered
4/03/2013
Date last updated
26/07/2017

Titles & IDs
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
Secondary ID [1] 0 0
117016
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK239512
Treatment: Drugs - ketoconazole

Active Comparator: Session 1 or Session 2 - Single dose sessions without ketoconazole co-administration

Active Comparator: Co-dose Session - Single dose session with ketoconazole co-administration


Treatment: Drugs: GSK239512
H3 receptor antagonist, potential victim of drug-drug interaction

Treatment: Drugs: ketoconazole
CYP3A4 inhibitor, potential perpetrator of drug-drug interaction
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AUC of GSK239512
Timepoint [1] 0 0
Predose and up to 120 hour post dose of GSK239512
Primary outcome [2] 0 0
Cmax of GSK239512
Timepoint [2] 0 0
Predose and up to 120 hour post dose of GSK239512
Secondary outcome [1] 0 0
Number of participants with adverse events as a measure of safety and tolerability
Timepoint [1] 0 0
15 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/04/2013
Sample size
Target
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The study will determine the effect of 400 mg once daily of ketoconazole at steady state on
the pharmacokinetics of a single oral dose of GSK239512 in young healthy volunteers.
Ketoconazole is a strong inhibitor of CYP3A4, which is involved in metabolism of drugs. A
two-cohort design will be applied with cohort 1 aimed at providing a first estimate of the
interaction potential of GSK239512 and ketoconazole in terms of pharmacokinetic parameters in
a small number of subjects. Data from Cohort 1 will inform the decision of which dose to use
in Cohort 2, in which a larger number of subjects will be exposed to GSK239512 without and
with ketoconazole. The target maximum exposure is aimed to be similar to the exposure by a
single dose of 80 mcg of GSK239512 without CYP3A4 inhibition. In summary, the results from
this study will help to estimate the maximum increase in exposure of GSK239512 during
concomitant use of strong CYP3A4 inhibitors and will help define the subsequent dosing
strategy around GSK239512 and co-medications with potential to inhibit CYP3A4.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01802931
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01802931