Effect of Haemodialysis on the Pharmacokinetics of Ezogabine/Retigabine and Its N-acetyl Metabolite

NCT01480609 | Completed Phase 1

• 1 other identifier: 115214
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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. The doses of ezogabine/retigabine in the two treatment periods will be separated by at least 7 days.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (2)

• Clearance (Cl/F), clearance during dialysis (CLD) and fraction of total clearance attributed to dialysis (FD) of ezogabine/retigabine and NAMR

  Pharmacokinetic parameters

  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

  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

  Participants will be assessed for the duration of the study - an expected average of 3 weeks

Study Arms (2)

Dose-Dialysis

ACTIVE COMPARATOR

Subjects will be dosed with study drug followed by a scheduled dialysis session

Drug: Retigabine / Ezogabine

Dialysis-Dose

ACTIVE COMPARATOR

Subjects will be dosed following the completion of their scheduled dialysis session

Drug: Retigabine / Ezogabine

Interventions

Retigabine / Ezogabine DRUG

Retigabine / Ezogabine will be available as immediate release tablets of 50 milligrams strength. Subjects will be administered the tablet will 250 milliliters of water

Dialysis-Dose; Dose-Dialysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Minneapolis, Minnesota, 55404, United States

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 115214 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Epilepsy

Interventions

ezogabine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2011
• First Posted: November 29, 2011
• Study Start: November 30, 2011
• Primary Completion: April 24, 2012
• Study Completion: April 24, 2012
• Last Updated: June 19, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)