Pharmacokinetic Study of Retigabine Extended Release (XR) Formulation in Healthy Adult Japanese and Caucasian Subjects

This study has been withdrawn prior to enrollment.
(Development plan of retigabine XR in Japan was readjusted.)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01691872
First received: September 13, 2012
Last updated: July 16, 2013
Last verified: July 2013
  Purpose

This is an open-label, single centre, parallel group study to evaluate the safety and pharmacokinetics of single oral doses of retigabine XR formulation in healthy adult Japanese subjects. To compare the pharmacokinetic and safety profile, Caucasian subjects are also incorporated. This study is intended to facilitate inclusion of Japanese patients in the global phase III program for retigabine XR formulation.


Condition Intervention Phase
Epilepsy, Partial
Drug: Retigabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: An Open-label, Single Centre, Parallel Group Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of Retigabine Extended Release (XR) Formulation in Healthy Adult Japanese and Caucasian Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • AUC0-∞ of retigabine [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of retigabine

  • Cmax of retigabine [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Maximum observed concentration of retigabine

  • Tmax of retigabine [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Time of occurance of Cmax of retigabine

  • t1/2 of retigabine [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Terminal phase half-life of retigabine

  • Adverse Events [ Time Frame: up to 96h post dose ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events as a measure of safety and tolerability (evaluated by the result of Clinical safety laboratory tests, vital signs, 12-lead ECG, telemetry and clinical monitoring/observation


Secondary Outcome Measures:
  • AUC0-∞ of NAMR [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of NAMR

  • Cmax of NAMR [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Maximum observed concentration of NAMR

  • Tmax of NAMR [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Time of occurance of Cmax of NAMR

  • t1/2 of NAMR [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Terminal phase half-life of NAMR

  • fe [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Percent of retigabine and NAMR excreted in urine

  • CLr [ Time Frame: up to 96h post dose ] [ Designated as safety issue: No ]
    Renal clearance of retigabine and NAMR


Enrollment: 0
Study Start Date: October 2012
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Japanese
Retigabine 300mg single-dose
Drug: Retigabine
Retigabine
Experimental: Caucasian
Retigabine 300mg single-dose
Drug: Retigabine
Retigabine

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male subject between 20 and 45 years of age inclusive, at the time of signing the informed consent.
  • Japanese ancestry defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. OR Caucasian defined as an individual having four grandparents who are all descendents of the original people of Europe.
  • 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).
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed separately. This criterion must be followed from the time of the first dose of study medication until 1 week post-last dose
  • 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%).
  • Single QTcB or QTcF< 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

  • 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, Hepatitis C antibody or HIV antigen/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.
  • 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.
  • 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 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 56 day period.
  • 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.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691872

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01691872     History of Changes
Other Study ID Numbers: 116247
Study First Received: September 13, 2012
Last Updated: July 16, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Epilepsies, Partial
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Ezogabine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014