EpilepsyPhase 1NCT01480609
Effect of Haemodialysis on the Pharmacokinetics of Ezogabine/Retigabine and Its N-acetyl Metabolite
A Phase 1 study testing Retigabine / Ezogabine in people with Epilepsy, run by GlaxoSmithKline at 1 site in United States.
Trial summary
This in an open-label, single dose, fixed sequence, two treatment period study enrolling 8 patients (to obtain 6 evaluable) with end stage renal disease (ESRD) receiving haemodialysis. Patients will remain in the unit during each treatment period from admission to the collection of the final PK sample. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsy
- What is being tested?
- Retigabine / Ezogabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2011to 24 Apr 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female 18 years or older, at the time of signing the informed consent.
- ESRD patients with minimal or no residual renal function and receiving stabilised haemodialysis regimen.
- Body mass index with the range of 18-42 kg/m2 at screening.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods listed.
- Child-bearing potential and agrees to use one of the contraception methods listed. Female subjects must agree to use contraception until at least 1 week post-last dose.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed. This criterion must be followed from the time of the first dose of study medication until at least 1 week post-last dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- Subjects with fluctuating or rapidly deteriorating condition that is not adequately controlled by medications
- Subjects with signs of a clinically significant infection.
- Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
- Subjects with any other medical condition which, in the judgement of the investigator and medical monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject
- Clinically relevant laboratory or physical examination abnormalities (except for renal function tests or deviation of clinical laboratory values that are related to renal impairment).
- Subjects with blood pressure, after resting for ≥ 3 minutes, higher than 160/95 mmHg or lower than 100/50 mmHg. The patients receiving anthihypertensive treatment need to be on a stabilised treatment for three months.
Show all 23Show fewer
- The screening ECGs measurements must be within the limit indicated in the protocol.
- Any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety for the individual subject.
- History of hemoglobinopathy.
- A radiological test involving contrast dye within 4 weeks prior to screening.
- Poor peripheral venous access.
- 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.
- History of regular alcohol consumption within 6 months of the study.
- 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.
- 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.
- Pregnant females
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
Trial locations and contacts
1 site in 1 country.
United States1 site
GSK Investigational Site
Minneapolis, Minnesota, 55404
About this study
Official title: An Open Label, Single-dose, Fixed Sequence, Two Treatment Period Study to Assess the Effect of Haemodialysis on the Pharmacokinetics of Ezogabine/Retigabine and the N-acetyl Metabolite of Ezogabine/Retigabine (NAMR).
This in an open-label, single dose, fixed sequence, two treatment period study enrolling 8 patients (to obtain 6 evaluable) with end stage renal disease (ESRD) receiving haemodialysis. Patients will remain in the unit during each treatment period from admission to the collection of the final PK sample. The doses of ezogabine/retigabine in the two treatment periods will be separated by at least 7 days.
Read the detailed description
Treatment Period 1: Subjects will be admitted on Day -1 when baseline assessments will be performed. On Day 1 subjects will receive a single dose of 100mg ezogabine/retigabine immediate release (IR) and dialysis will start 4 hours post-dose. Pharmacokinetic (PK) samples will be collected up to approximately 68 hours post-dose.
Samples of dialysate will be collected in 0-1, 1-2, 2-3, and 3-4 hour (if available) aliquots, timed from the start of dialysis. The volume of dialysate collected in each aliquot will be recorded.
Four samples of predialyzer ("arterial" line) blood and four samples of postdialyzer ("venous" line) blood will be obtained during the haemodialysis procedure at approximately one hour intervals starting immediately prior to the start of the procedure and finishing at the end of the procedure.
Subjects will be discharged from the unit following the collection of the last PK sample.
Treatment Period 2: Subjects will be admitted on Day -1 when baseline assessments will be performed. On Day 1 following the completion of their scheduled dialysis session subjects will receive a single dose of 100mg ezogabine/retigabine IR. PK samples will be collected up to approximately 68 hours post-dose.
Subjects will be discharged from the unit following the collection of the last PK sample.
In both treatment periods, PK blood samples will be obtained pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60 and 68 hours (or just prior next dialysis session - whichever is sooner) post-dose. Subjects will be discharged after the final post-dose draw.
- Conditions
- Epilepsy
- Being tested
- Retigabine / Ezogabine
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retigabine / EzogabineDrug
Retigabine / Ezogabine will be available as immediate release tablets of 50 milligrams strength. Subjects will be administered the tablet will 250 milliliters of water
| Study group | Role | What they receive |
|---|---|---|
| Dose-Dialysis | Active comparator | Subjects will be dosed with study drug followed by a scheduled dialysis session Receives: Drug: Retigabine / Ezogabine |
| Dialysis-Dose | Active comparator | Subjects will be dosed following the completion of their scheduled dialysis session Receives: Drug: Retigabine / Ezogabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clearance (Cl/F), clearance during dialysis (CLD) and fraction of total clearance attributed to dialysis (FD) of ezogabine/retigabine and NAMR
Pharmacokinetic parameters
Measured: During Dialysis (0-1, 1-2, 2-3, and 3-4 hour)
AUC(0-t), AUC (0-∞), T½, Cmax, Tmax of ezogabine/retigabine and NAMR in plasma. Amount of ezogabine/retigabine and NAMR cleared by dialysis (AD)
Pharmacokinetic parameters
Measured: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60 and 68 hours
Secondary outcomes (1)
Nmber of Safety and tolerability parameters, including adverse event, clinical laboratory, and vital signs assessments
Safety Parameters
Measured: Participants will be assessed for the duration of the study - an expected average of 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2011 (estimated)
- Study start30 Nov 2011
- Primary completion24 Apr 2012
- Study completion24 Apr 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
- 8 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
- NCT01480609
- Sponsor's protocol ID
- 115214
- 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, Single-dose, Fixed Sequence, Two Treatment Period Study to Assess the Effect of Haemodialysis on the Pharmacokinetics of Ezogabine/Retigabine and the N-acetyl Metabolite of Ezogabine/Retigabine (NAMR).
- ClinicalTrials.gov ID
- NCT01480609
- Acronym / sponsor ID
- 115214
- Conditions
- Epilepsy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2011 (actual)
- Primary completion
- 24 Apr 2012 (actual)
- Study completion
- 24 Apr 2012 (actual)
- First posted
- 29 Nov 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.
This in an open-label, single dose, fixed sequence, two treatment period study enrolling 8 patients (to obtain 6 evaluable) with end stage renal disease (ESRD) receiving haemodialysis. Patients will remain in the unit during each treatment period from admission to the collection of the final PK sample. The doses of ezogabine/retigabine in the two treatment periods will be separated by at least 7 days.
Detailed description
Treatment Period 1: Subjects will be admitted on Day -1 when baseline assessments will be performed. On Day 1 subjects will receive a single dose of 100mg ezogabine/retigabine immediate release (IR) and dialysis will start 4 hours post-dose. Pharmacokinetic (PK) samples will be collected up to approximately 68 hours post-dose.
Samples of dialysate will be collected in 0-1, 1-2, 2-3, and 3-4 hour (if available) aliquots, timed from the start of dialysis. The volume of dialysate collected in each aliquot will be recorded.
Four samples of predialyzer ("arterial" line) blood and four samples of postdialyzer ("venous" line) blood will be obtained during the haemodialysis procedure at approximately one hour intervals starting immediately prior to the start of the procedure and finishing at the end of the procedure.
Subjects will be discharged from the unit following the collection of the last PK sample.
Treatment Period 2: Subjects will be admitted on Day -1 when baseline assessments will be performed. On Day 1 following the completion of their scheduled dialysis session subjects will receive a single dose of 100mg ezogabine/retigabine IR. PK samples will be collected up to approximately 68 hours post-dose.
Subjects will be discharged from the unit following the collection of the last PK sample.
In both treatment periods, PK blood samples will be obtained pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60 and 68 hours (or just prior next dialysis session - whichever is sooner) post-dose. Subjects will be discharged after the final post-dose draw.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose-Dialysis | Active comparator | Drug: Retigabine / EzogabineSubjects will be dosed with study drug followed by a scheduled dialysis session |
| Dialysis-Dose | Active comparator | Drug: Retigabine / EzogabineSubjects will be dosed following the completion of their scheduled dialysis session |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female 18 years or older, at the time of signing the informed consent.
- ESRD patients with minimal or no residual renal function and receiving stabilised haemodialysis regimen.
- Body mass index with the range of 18-42 kg/m2 at screening.
- A female subject is eligible to participate if she is of:
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed. This criterion must be followed from the time of the first dose of study medication until at least 1 week post-last dose.
Key exclusion criteria (23 listed)
- Subjects with fluctuating or rapidly deteriorating condition that is not adequately controlled by medications
- Subjects with signs of a clinically significant infection.
- Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
- Subjects with any other medical condition which, in the judgement of the investigator and medical monitor, could jeopardize the integrity of the data derived from that subject or the safety of the subject
- Clinically relevant laboratory or physical examination abnormalities (except for renal function tests or deviation of clinical laboratory values that are related to renal impairment).
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 |
|---|---|---|
| Retigabine / EzogabineRetigabine / Ezogabine will be available as immediate release tablets of 50 milligrams strength. Subjects will be administered the tablet will 250 milliliters of water | Drug | Dialysis-Dose, Dose-Dialysis |
Primary outcome
Clearance (Cl/F), clearance during dialysis (CLD) and fraction of total clearance attributed to dialysis (FD) of ezogabine/retigabine and NAMR
Time frame: During Dialysis (0-1, 1-2, 2-3, and 3-4 hour)
Pharmacokinetic parameters
AUC(0-t), AUC (0-∞), T½, Cmax, Tmax of ezogabine/retigabine and NAMR in plasma. Amount of ezogabine/retigabine and NAMR cleared by dialysis (AD)
Time frame: 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60 and 68 hours
Pharmacokinetic parameters
1 secondary outcome
Nmber of Safety and tolerability parameters, including adverse event, clinical laboratory, and vital signs assessments
Time frame: Participants will be assessed for the duration of the study - an expected average of 3 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.
- 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 115214 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 Epilepsy
Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy
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 Retigabine / Ezogabine in people with Epilepsy, run by GlaxoSmithKline at 1 site in United States.
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 8 inclusion and 23 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 United States. 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?
Clearance (Cl/F), clearance during dialysis (CLD) and fraction of total clearance attributed to dialysis (FD) of ezogabine/retigabine and NAMR (time frame: During Dialysis (0-1, 1-2, 2-3, and 3-4 hour)). 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 19 Jun 2018.