GSK Drug Single Dose Escalation And Their Effect On Resting Motor Threshold In Healthy Volunteers

October 25, 2017 updated by: Biogen

Double Blind, Randomised, Placebo Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Doses of GSK Drug and the Effect of Single Doses of GSK Drug or Lamotrigine on Resting Motor Threshold in Healthy Volunteers

This is a First Time in Human Study to assess the safety, tolerability, pharmacokinetics and resting motor threshold (rMT) of single doses of GSK drug in healthy volunteers.This will be a 2 part and 2 centre study.Part 1 will be a double-blind, randomized, placebo-controlled, single oral dose, dose-rising, cross-over study in healthy male and female (of non-child bearing potential) volunteers.Subjects will be randomized into cohorts of 10 subjects and cohorts will be recruited until the pre-defined safety or PK stopping limits are reached.Each subject will receive placebo and no more than 4 ascending doses of GSK drug in a randomized sequence on 5 separate study occasions.Each dosing session will take place over 2 days and there will be at least one subject on placebo on each day. There will be only one subject on any new active dose during the first day.Part 2 will be a randomised, double-blind, double-dummy, placebo-controlled, cross-over study to investigate the effect of single doses of GSK drug and lamotrigine on resting motor threshold in healthy male subjects. Subjects will attend the unit a maximum of 4 separate occasions.During each session subjects will receive up to 4 TMS measurements and single doses of either GSK drug, lamotrigine or placebo, in a randomised manner.Up to two doses of GSK drug will be investigated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study, previously posted by GlaxoSmithKline (GSK), was transitioned to Convergence Pharmaceuticals, Ltd., which spun off from GSK. Convergence Pharmaceuticals, Ltd., has now been acquired by Biogen.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SE1 1YR
        • GSK Investigational Site
    • Middlesex
      • Harrow, Middlesex, United Kingdom, HA13UJ
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Part 1 Inclusion Criteria:

  • Healthy male subjects aged between 18 and 65 yrs and female (of non-child bearing potential) subjects aged between 18 and 50 years.

Part 2 Inclusion Criteria:

  • right-handed healthy male subjects aged between 18 and 65 years.

Parts 1 & 2 Inclusion Criteria:

  • body weight >50 kg and Body Mass Index (BMI) within the range 19 - 29.9 kg/m2 inclusive.
  • No abnormality on relevant clinical examination.
  • No abnormality on relevant clinical chemistry or haematology examination at the pre-study medical examination.
  • A 12-lead ECG at the pre-study medical examination which is normal.
  • Non-smokers.
  • Signed and dated written informed consent prior to any study procedures being done.
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Parts 1&2 Exclusion Criteria:

  • exceeding weekly recommended alcohol intake.
  • An unwillingness of a male subject to use a condom/ spermicide in addition to having their female partner use another form of contraception.
  • A positive Hepatitis B surface antigen, Hepatitis C antibody, and Human Immunodeficiency Virus (HIV) antibody result at screening.
  • A positive urine drug test at screening or prior to each treatment period.
  • History of alcohol/drug abuse or dependence within 12 months of the study.
  • Urine cotinine levels indicative of smoking.
  • History or regular use of tobacco or nicotine containing products within 6 months prior to screening.
  • QTc interval > 450 ms.
  • Current or past history of symptomatic orthostatic hypotension. Sitting systolic blood pressure >139 or <90 mmHg and/or diastolic blood pressure >100 or <50 mmHg. Standing heart rate <45 bpm.
  • The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
  • Exposure to more than four new chemical entities within 12 months prior to the first dose of current study medication. 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 sponsor the medication will not interfere with the study procedures or compromise subject safety.
  • Consumption of moderate/high tyramine containing food or drinks from 1 week prior to the first dose and until discharge, following the last dose.
  • History of hypersensitivity to lamotrigine.
  • History of sensitivity to any of the study medications, or components thereof.Or a history of drug, cosmetic or other allergy that, in the opinion of the physician, might interfere with the conduct of the study.
  • History of known or suspected seizures, including infantile febrile, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits).
  • Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.

Part 2 Exclusion Criteria:

  • History of clinically relevant skin rashes and allergies.
  • Poorly-controlled migraine headaches.
  • Implanted metal devices including pacemakers.
  • Previous brain neurosurgery.
  • History of neurological disorders and stroke.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Part 1
Single dose escalation
Other: Placebo
Placebo
Drug: GSK drug
GSK drug
Other Names:
  • BIIB074 and CNV1014802
Other: Part 2
Pharmacodynamic assessment
Other: Placebo
Placebo
Drug: GSK drug
GSK drug
Other Names:
  • BIIB074 and CNV1014802
Other: Lamictal
Positive control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part1:AEs for the duration of the study;
Time Frame: duration of the study
duration of the study
ECG,vitals and MAO activity predose and upto 48h post dose;
Time Frame: predose and upto 48h post dose
predose and upto 48h post dose
clinical labs predose and upto 24h post dose.
Time Frame: predose and upto 24h post dose
predose and upto 24h post dose
PK parameters up to 48h post dose.
Time Frame: up to 48h post dose
up to 48h post dose
Part2:Difference in rMT between pre-and post-dose and relationship with PK.
Time Frame: between pre-and post-dose and relationship with PK
between pre-and post-dose and relationship with PK

Secondary Outcome Measures

Outcome Measure
Time Frame
Part1:Bond-Lader and body sway predose and upto 24h postdose.
Time Frame: predose and upto 24h postdose
predose and upto 24h postdose
Part2:AEs for the duration of the study;.
Time Frame: duration of the study
duration of the study
ECG,vitals and MAO activity predose and upto 48h postdose;
Time Frame: predose and upto 48h postdose
predose and upto 48h postdose
clinical labs predose and upto 24h postdose
Time Frame: predose and upto 24h postdose
predose and upto 24h postdose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Investigators

  • Study Director: Biogen Medical Director, Biogen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 31, 2007

Primary Completion (Actual)

May 31, 2008

Study Completion (Actual)

May 31, 2008

Study Registration Dates

First Submitted

June 18, 2007

First Submitted That Met QC Criteria

June 19, 2007

First Posted (Estimate)

June 20, 2007

Study Record Updates

Last Update Posted (Actual)

October 26, 2017

Last Update Submitted That Met QC Criteria

October 25, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCB107718

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe