Multiple SclerosisPhase 1NCT01802931
GSK239512 DDI Study
A Phase 1 study testing GSK239512 and ketoconazole in people with Multiple Sclerosis, run by GlaxoSmithKline at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- GSK239512 and ketoconazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteAustralia
- Study dates
- 7 Jan 2013to 15 Apr 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 29Show fewer
- 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).
- 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).
- 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.
- The subject has a history of significant psychiatric illness.
- Presence or history of hallucinations that, in the judgement of the investigator, may increase the safety risk to the subject.
- 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.
- Diagnosis of any type epilepsy
- Night shift workers within 4 weeks of first dosing
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label Study in Healthy Volunteers to Investigate the Effect of Ketoconazole on the Pharmacokinetics of GSK239512
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
- Being tested
- GSK239512, ketoconazole
- Keywords
- GSK239512, H3 receptor antagonist, drug-drug interaction, pharmacokinetics, ketoconazole
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK239512Drug
H3 receptor antagonist, potential victim of drug-drug interaction
ketoconazoleDrug
CYP3A4 inhibitor, potential perpetrator of drug-drug interaction
| Study group | Role | What they receive |
|---|---|---|
| Session 1 or Session 2 | Active comparator | Single dose sessions without ketoconazole co-administration Receives: Drug: GSK239512 |
| Co-dose Session | Active comparator | Single dose session with ketoconazole co-administration Receives: Drug: GSK239512; Drug: ketoconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC of GSK239512
Measured: Predose and up to 120 hour post dose of GSK239512
Cmax of GSK239512
Measured: 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
Measured: 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2013 (estimated)
- Study start7 Jan 2013
- Primary completion15 Apr 2013
- Study completion15 Apr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01802931
- Sponsor's protocol ID
- 117016
- Status last verified
- Jul 2017
- First submitted
- 4 Jan 2013
- Last updated
- 26 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study in Healthy Volunteers to Investigate the Effect of Ketoconazole on the Pharmacokinetics of GSK239512
- ClinicalTrials.gov ID
- NCT01802931
- Acronym / sponsor ID
- 117016
- Conditions
- Multiple Sclerosis
- Keywords
- GSK239512, H3 receptor antagonist, drug-drug interaction, pharmacokinetics, ketoconazole
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 7 Jan 2013 (actual)
- Primary completion
- 15 Apr 2013 (actual)
- Study completion
- 15 Apr 2013 (actual)
- First posted
- 4 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Session 1 or Session 2 | Active comparator | Drug: GSK239512Single dose sessions without ketoconazole co-administration |
| Co-dose Session | Active comparator | Drug: GSK239512, Drug: ketoconazoleSingle dose session with ketoconazole co-administration |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK239512H3 receptor antagonist, potential victim of drug-drug interaction | Drug | Co-dose Session, Session 1 or Session 2 |
| ketoconazoleCYP3A4 inhibitor, potential perpetrator of drug-drug interaction | Drug | Co-dose Session |
Primary outcome
AUC of GSK239512
Time frame: Predose and up to 120 hour post dose of GSK239512
Cmax of GSK239512
Time frame: Predose and up to 120 hour post dose of GSK239512
1 secondary outcome
Number of participants with adverse events as a measure of safety and tolerability
Time frame: 15 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2017.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 117016 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Related trials for Multiple Sclerosis
Recruiting
Dry Needling in Multiple Sclerosis
Multiple Sclerosis
RecruitingObservational study
Study of the Disease Process of Lymphangioleiomyomatosis
Lung Disease, Pneumothorax
RecruitingPhase 2
A Study to Evaluate Pharmacokinetics (PK) and Safety of Subcutaneous (SC) Ublituximab Administered at Various Injection Sites and Relative Bioavailability Via Autoinjector (AI) Versus Syringe Subcutaneously in Participants With Multiple Sclerosis (MS)
Multiple Sclerosis
Active, not recruitingPhase 2
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Tuberous Sclerosis Complex, Epilepsy
RecruitingObservational study
Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
Progressive Multifocal Leukoencephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK239512 and ketoconazole in people with Multiple Sclerosis, run by GlaxoSmithKline at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC of GSK239512 (time frame: Predose and up to 120 hour post dose of GSK239512). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2017.