Effect of GSK1014802 on Electrical Hyperalgesia and Threshold Tracking in Healthy Subjects

NCT00964288 | Terminated Phase 1

• 2 other identifiers: 111676NP111676
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being conducted to assess the effects of GSK1014802 and a positive control, lidocaine, on tests of peripheral nerve excitability. This will be a double blind, placebo controlled, 4-period cross over study. Approximately 20 subjects will be randomised to one of two doses of a GSK1014802, lidocaine and placebo with at least 2 weeks between sessions. A follow-up will occur 7-15 days after the last dose. During treatment session 3 on the 6th October 2009, one subject had a pattern of AEs of severe intensity, suggestive of brain stem toxicity / encephalopathy during the lidocaine/saline infusion period. Although recognised in the literature when lidocaine was used in patients for treatment of pain, these AEs were unusual in studies in healthy subjects. The study was suspended to allow re-evaluation of the risk:benefit balance of lidocaine/saline infusion in healthy subjects in this study. It was decided that continuation of the use of lidocaine (positive control) would risk the safety of subjects. Continuation without the positive control was not possible as it would compromise the scientific integrity of the design.

Conditions

Pain, Neuropathic; Neuropathic Pain

Keywords

electrical hyperalgesia; threshold tracking; pain

Outcome Measures

Primary Outcomes (1)

• To determine the effect of single oral doses of GSK1014802 on area of flare evoked by cutaneous electrical stimulation.

  16 weeks

Secondary Outcomes (3)

• To determine the effect of single oral doses of GSK1014802 and a single i.v. infusion of lidocaine on tests of nerve excitability

  16 weeks

• To further investigate the safety and tolerability of single oral doses of GSK1014802

  16 weeks

• To assess relationships between GSK1014802 pharmacokinetics and pharmacodynamic endpoints.

  16 weeks

Study Arms (4)

Period 1

OTHER

Drug: GSK1014802 low dose; Drug: Lidocaine; Drug: GSK1014802 high dose; Drug: Placebo

Period 2

OTHER

Drug: GSK1014802 low dose; Drug: Lidocaine; Drug: GSK1014802 high dose; Drug: Placebo

Period 3

OTHER

Drug: GSK1014802 low dose; Drug: Lidocaine; Drug: GSK1014802 high dose; Drug: Placebo

Period 4

OTHER

Drug: GSK1014802 low dose; Drug: Lidocaine; Drug: GSK1014802 high dose; Drug: Placebo

Interventions

GSK1014802 low dose DRUG

oral tablet

Also known as: BIIB074 and CNV1014802

Period 1; Period 2; Period 3; Period 4

Lidocaine DRUG

positive control

Period 1; Period 2; Period 3; Period 4

GSK1014802 high dose DRUG

oral tablet

Also known as: BIIB074 and CNV1014802

Period 1; Period 2; Period 3; Period 4

Placebo DRUG

To match GSK drug and positive control

Period 1; Period 2; Period 3; Period 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male between 18 and 55 years of age inclusive.
• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN
• Healthy as determined by a responsible and experienced physician.
• Male subjects must agree to use one of the contraception methods requested.
• Body weight greater than or equal to 50 kg, BMI ≤29.9kg/m2
• Capable of giving written informed consent.
• QTcB or QTcF \< 450 msec.

You may not qualify if:

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result.
• 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.
• Heart block, bundle branch block, hemi-block, evidence of accessory cardiac conduction pathways, long pauses \>2 s or other cardiac conduction abnormalities or cardiac arrhythmias on 12-lead ECG or 24 h Holter at screening.
• History of regular excessive alcohol consumption within 6 months of the study.
• The subject has participated in a clinical trial and has received an investigational product within 90 days o fthe strat of this study.
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• 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.
• 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 a 56 day period.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• Subjects with a history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.

Sponsors & Collaborators

• Biogen: lead

MeSH Terms

Conditions

Neuralgia; Pain

Interventions

vixotrigine; Lidocaine

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Biogen Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: August 24, 2009
• Study Start: July 31, 2009
• Primary Completion: November 30, 2009
• Study Completion: November 30, 2009
• Last Updated: October 26, 2017

Record last verified: 2017-10