Last updated: 11/07/2018 08:57:30

Effect of haemodialysis on the pharmacokinetics of ezogabine/retigabine and its n-acetyl metabolite

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GSK study ID
115214
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Clinicaltrials.gov ID
NCT01480609
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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).
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

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

Timeframe: 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)

Timeframe: 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:

Nmber of Safety and tolerability parameters, including adverse event, clinical laboratory, and vital signs assessments

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

Interventions:
  • Drug: Retigabine / Ezogabine
    • Enrollment:
    8
    Primary completion date:
    Not applicable
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Epilepsy
    Product
    retigabine
    Collaborators
    Not applicable
    Study date(s)
    November 2011 to April 2012
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • 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.
    • Subjects with fluctuating or rapidly deteriorating condition that is not adequately controlled by medications
    • Subjects with signs of a clinically significant infection.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • 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.
    Exclusion criteria:
    • 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.
    • 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 location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Minneapolis, Minnesota, United States, 55404
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    Study complete
    Actual primary completion date
    Not applicable
    Actual study completion date
    2012-24-04

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

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