GSK239512 DDI Study

NCT01802931 | Completed Phase 1

• 1 other identifier: 117016
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

GSK239512; H3 receptor antagonist; drug-drug interaction; pharmacokinetics; ketoconazole

Outcome Measures

Primary Outcomes (2)

• AUC of GSK239512

  Predose and up to 120 hour post dose of GSK239512

• Cmax of GSK239512

  Predose and up to 120 hour post dose of GSK239512

Secondary Outcomes (1)

• Number of participants with adverse events as a measure of safety and tolerability

  15 weeks

Study Arms (2)

Session 1 or Session 2

ACTIVE COMPARATOR

Single dose sessions without ketoconazole co-administration

Drug: GSK239512

Co-dose Session

ACTIVE COMPARATOR

Single dose session with ketoconazole co-administration

Drug: GSK239512; Drug: ketoconazole

Interventions

GSK239512 DRUG

H3 receptor antagonist, potential victim of drug-drug interaction

Co-dose Session; Session 1 or Session 2

ketoconazole DRUG

CYP3A4 inhibitor, potential perpetrator of drug-drug interaction

Co-dose Session

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male between 18 and 45 years of age inclusive, at the time of signing the informed consent.
• 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.
• ALT, alkaline phosphatase and bilirubin \< or = 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• QTcF \< 450 msec.
• 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.
• Body weight \> 50 kg, and body mass index (BMI) between 19.0 - 29.9 kg/m2 inclusive.
• Capable of giving informed consent and can comply with the study requirements and timetable.

You may not qualify if:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• Current or 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 Human Immunodeficiency Virus (HIV) antibody.
• 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.
• History of smoking cigarettes or using tobacco products or any nicotine-containing products (including nicotine patches) within 3 months of screening.
• 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.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• 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.
• 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.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 117016 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

GSK239512; Ketoconazole

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2013
• First Posted: March 4, 2013
• Study Start: January 7, 2013
• Primary Completion: April 15, 2013
• Study Completion: April 15, 2013
• Last Updated: July 26, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)