EpilepsyPhase 1NCT01462669
Crossover Study to Evaluate the Pharmacokinetics of Ezogabine/Retigabine in Taiwanese Subjects
A Phase 1 study testing 50mg Ezogabine/retigabine, 100mg Ezogabine/retigabine and 200mg Ezogabine/retigabine in people with Epilepsy, run by GlaxoSmithKline at 1 site in Taiwan.
Trial summary
The purpose of this study is to investigate the pharmacokinetics of single oral doses of ezogabine/retigabine and the primary metabolite (NAMR) in healthy male and female Taiwanese volunteers. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Epilepsy
- What is being tested?
- 50mg Ezogabine/retigabine, 100mg Ezogabine/retigabine and 200mg Ezogabine/retigabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteTaiwan
- Study dates
- 10 Apr 2012to 27 Jun 2012
- 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 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Male or female between 20 and 65 years of age inclusive, at the time of signing the informed consent.
- Taiwanese ancestry defined as being born in Taiwan, having four ethnic Chinese/Taiwanese grandparents, holding a Taiwanese passport or identity papers and subject is able to speak Chinese/Taiwanese.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. 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.
- Body weight ≥ 50 kg and BMI within the range 18.5-24.9 kg/m2 (inclusive).
- A female subject is eligible to participate if she is of:
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- Non-childbearing potential 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) > 40 MlU/ml and estradiol <40 pg/ml (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 1 week post-last dose of GW582892.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Normal ECG morphology and measurements. In particular QTcB or QTcF < 450 msec or QTc < 480 msec in subjects with Bundle Branch Block based on an average from three ECGs obtained over a brief recording period.
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Subject has made a suicide attempt in the past or, in the investigator's judgment, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior in the past 6 months and/or any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS).
- 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 HIV antibody.
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- History of regular alcohol consumption within 6 months of the study defined as:
- An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 360 ml of beer, 150 ml of table wine or 45 ml of 80 proof distilled 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 assessments 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 56 day period.
- Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Subjects who have asthma or a history of asthma.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomized, Single Centre, 4-way Crossover Study to Evaluate the Pharmacokinetics of Single Oral Doses of Ezogabine/Retigabine in Healthy Adult Taiwanese Subjects
The purpose of this study is to investigate the pharmacokinetics of single oral doses of ezogabine/retigabine and the primary metabolite (NAMR) in healthy male and female Taiwanese volunteers. Subjects will receive four separate doses of ezogabine/retigabine tablets: 50 mg, 100 mg, 200 mg and 400 mg administered once orally. Blood samples will be obtained at pre-defined timepoints over the duration of the study to determine the concentration of ezogabine/retigabine and NAMR. Safety assessments will include measurements of vital signs, collection of adverse events, clinical laboratory tests and the Columbia Suicide Severity Rating Scale.
Read the detailed description
Ezogabine/retigabine (GW582892), N-[2-amino-4(4-fluorobenzylamino)-phenyl] carbamic acid ethyl ester, is a novel anti-epileptic compound which has been developed as an adjunctive treatment for partial onset seizures in patients with refractory epilepsy.
This is an open-label, randomized, single-center, 4-way crossover study to investigate the pharmacokinetics of single oral doses of ezogabine/retigabine and the n-acetyl metabolite of ezogabine/retigabine (NAMR) in healthy male and female Taiwanese volunteers. The study consists of a screening phase, 4 treatment periods and a follow-up visit. Subjects will receive each of the following four treatments administered in a randomized four-way crossover design: 50 mg, 100 mg, 200 mg and 400 mg ezogabine/retigabine tablets administered once orally. Serial blood samples will be obtained at pre-defined timepoints for pharmacokinetic analysis of ezogabine/retigabine and NAMR. Safety assessments will include measurements of vital signs, collection of adverse events, clinical laboratory tests and the Columbia Suicide Severity Rating Scale.
- Conditions
- Epilepsy
- Being tested
- 50mg Ezogabine/retigabine, 100mg Ezogabine/retigabine, 200mg Ezogabine/retigabine, 400mg Ezogabine/retigabine
- Keywords
- Ezogabine, Pharmacokinetics, Retigabine
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
50mg Ezogabine/retigabineDrug
Also called GW582892
A single 50mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state
100mg Ezogabine/retigabineDrug
Also called GW582892
A single 100mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state
200mg Ezogabine/retigabineDrug
Also called GW582892
A single 200mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state
400mg Ezogabine/retigabineDrug
Also called GW582892
A single 400mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state
| Study group | Role | What they receive |
|---|---|---|
| Treatment Period 1 | Other | A single 50mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state Receives: Drug: 50mg Ezogabine/retigabine |
| Treatment Period 2 | Other | A single 100mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state Receives: Drug: 100mg Ezogabine/retigabine |
| Treatment Period 3 | Other | A single 200mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state Receives: Drug: 200mg Ezogabine/retigabine |
| Treatment Period 4 | Other | A single 400mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state Receives: Drug: 400mg Ezogabine/retigabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of single oral doses of ezogabine/retigabine and NAMR over the range of 50mg to 400mg in healthy male and female Taiwanese volunteers
Peak plasma concentration (Cmax) of ezogabine/retigabine; and area under the plasma concentration-time curve from time zero to infinity (AUC(0-∞)) for ezogabine/retigabine
Measured: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 14 weeks
Secondary outcomes (2)
Pharmacokinetics of single oral doses of ezogabine/retigabine and NAMR over the range of 50mg to 400mg in healthy male and female Taiwanese volunteers
Time to peak plasma concentration (Tmax) of ezogabine/retigabine; Terminal phase half-life (t½) of ezogabine/retigabine; Cmax of NAMR; AUC(0-∞) for NAMR; and Tmax of NAMR
Measured: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 14 weeks
Safety and tolerability data after single oral doses of ezogabine/retigabine in healthy male and female Taiwanese volunteers
Safety and tolerability data as measured by adverse events, vital signs, ECGs, clinical laboratory measurements and C-SSRS
Measured: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2011 (estimated)
- Study start10 Apr 2012
- Primary completion27 Jun 2012
- Study completion27 Jun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 1 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
- NCT01462669
- Sponsor's protocol ID
- 115860
- Status last verified
- Jun 2018
- First submitted
- 27 Oct 2011
- Last updated
- 19 Jun 2018
- 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 19 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, Single Centre, 4-way Crossover Study to Evaluate the Pharmacokinetics of Single Oral Doses of Ezogabine/Retigabine in Healthy Adult Taiwanese Subjects
- ClinicalTrials.gov ID
- NCT01462669
- Acronym / sponsor ID
- 115860
- Conditions
- Epilepsy
- Keywords
- Ezogabine, Pharmacokinetics, Retigabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 10 Apr 2012 (actual)
- Primary completion
- 27 Jun 2012 (actual)
- Study completion
- 27 Jun 2012 (actual)
- First posted
- 31 Oct 2011 (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 purpose of this study is to investigate the pharmacokinetics of single oral doses of ezogabine/retigabine and the primary metabolite (NAMR) in healthy male and female Taiwanese volunteers. Subjects will receive four separate doses of ezogabine/retigabine tablets: 50 mg, 100 mg, 200 mg and 400 mg administered once orally. Blood samples will be obtained at pre-defined timepoints over the duration of the study to determine the concentration of ezogabine/retigabine and NAMR. Safety assessments will include measurements of vital signs, collection of adverse events, clinical laboratory tests and the Columbia Suicide Severity Rating Scale.
Detailed description
Ezogabine/retigabine (GW582892), N-[2-amino-4(4-fluorobenzylamino)-phenyl] carbamic acid ethyl ester, is a novel anti-epileptic compound which has been developed as an adjunctive treatment for partial onset seizures in patients with refractory epilepsy.
This is an open-label, randomized, single-center, 4-way crossover study to investigate the pharmacokinetics of single oral doses of ezogabine/retigabine and the n-acetyl metabolite of ezogabine/retigabine (NAMR) in healthy male and female Taiwanese volunteers. The study consists of a screening phase, 4 treatment periods and a follow-up visit. Subjects will receive each of the following four treatments administered in a randomized four-way crossover design: 50 mg, 100 mg, 200 mg and 400 mg ezogabine/retigabine tablets administered once orally. Serial blood samples will be obtained at pre-defined timepoints for pharmacokinetic analysis of ezogabine/retigabine and NAMR. Safety assessments will include measurements of vital signs, collection of adverse events, clinical laboratory tests and the Columbia Suicide Severity Rating Scale.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment Period 1 | Other | Drug: 50mg Ezogabine/retigabineA single 50mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state |
| Treatment Period 2 | Other | Drug: 100mg Ezogabine/retigabineA single 100mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state |
| Treatment Period 3 | Other | Drug: 200mg Ezogabine/retigabineA single 200mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state |
| Treatment Period 4 | Other | Drug: 400mg Ezogabine/retigabineA single 400mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- Male or female between 20 and 65 years of age inclusive, at the time of signing the informed consent.
- Taiwanese ancestry defined as being born in Taiwan, having four ethnic Chinese/Taiwanese grandparents, holding a Taiwanese passport or identity papers and subject is able to speak Chinese/Taiwanese.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. 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.
- Body weight ≥ 50 kg and BMI within the range 18.5-24.9 kg/m2 (inclusive).
Key exclusion criteria (21 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- Subject has made a suicide attempt in the past or, in the investigator's judgment, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior in the past 6 months and/or any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS).
- 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.
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 |
|---|---|---|
| 50mg Ezogabine/retigabineAlso: GW582892A single 50mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state | Drug | Treatment Period 1 |
| 100mg Ezogabine/retigabineAlso: GW582892A single 100mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state | Drug | Treatment Period 2 |
| 200mg Ezogabine/retigabineAlso: GW582892A single 200mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state | Drug | Treatment Period 3 |
| 400mg Ezogabine/retigabineAlso: GW582892A single 400mg ezogabine/retigabine tablet will be administered orally with the subject in the fasted state | Drug | Treatment Period 4 |
Primary outcome
Pharmacokinetics of single oral doses of ezogabine/retigabine and NAMR over the range of 50mg to 400mg in healthy male and female Taiwanese volunteers
Time frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 14 weeks
Peak plasma concentration (Cmax) of ezogabine/retigabine; and area under the plasma concentration-time curve from time zero to infinity (AUC(0-∞)) for ezogabine/retigabine
2 secondary outcomes
Pharmacokinetics of single oral doses of ezogabine/retigabine and NAMR over the range of 50mg to 400mg in healthy male and female Taiwanese volunteers
Time frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 14 weeks
Safety and tolerability data after single oral doses of ezogabine/retigabine in healthy male and female Taiwanese volunteers
Time frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 14 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 19 Jun 2018.
- Results for study 115860 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- 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.
- 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.
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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 50mg Ezogabine/retigabine, 100mg Ezogabine/retigabine and 200mg Ezogabine/retigabine in people with Epilepsy, run by GlaxoSmithKline at 1 site in Taiwan.
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 11 inclusion and 21 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 19 Jun 2018. 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 Taiwan. 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?
Pharmacokinetics of single oral doses of ezogabine/retigabine and NAMR over the range of 50mg to 400mg in healthy male and female Taiwanese volunteers (time frame: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 14 weeks). 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 19 Jun 2018.