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

NCT ID: NCT00964288

Last Updated: 2017-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2009-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pain, Neuropathic Neuropathic Pain

Keywords

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electrical hyperalgesia threshold tracking pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Period 1

Group Type OTHER

GSK1014802 low dose

Intervention Type DRUG

oral tablet

Lidocaine

Intervention Type DRUG

positive control

GSK1014802 high dose

Intervention Type DRUG

oral tablet

Placebo

Intervention Type DRUG

To match GSK drug and positive control

Period 2

Group Type OTHER

GSK1014802 low dose

Intervention Type DRUG

oral tablet

Lidocaine

Intervention Type DRUG

positive control

GSK1014802 high dose

Intervention Type DRUG

oral tablet

Placebo

Intervention Type DRUG

To match GSK drug and positive control

Period 3

Group Type OTHER

GSK1014802 low dose

Intervention Type DRUG

oral tablet

Lidocaine

Intervention Type DRUG

positive control

GSK1014802 high dose

Intervention Type DRUG

oral tablet

Placebo

Intervention Type DRUG

To match GSK drug and positive control

Period 4

Group Type OTHER

GSK1014802 low dose

Intervention Type DRUG

oral tablet

Lidocaine

Intervention Type DRUG

positive control

GSK1014802 high dose

Intervention Type DRUG

oral tablet

Placebo

Intervention Type DRUG

To match GSK drug and positive control

Interventions

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GSK1014802 low dose

oral tablet

Intervention Type DRUG

Lidocaine

positive control

Intervention Type DRUG

GSK1014802 high dose

oral tablet

Intervention Type DRUG

Placebo

To match GSK drug and positive control

Intervention Type DRUG

Other Intervention Names

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BIIB074 and CNV1014802 BIIB074 and CNV1014802

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Average daily caffeine intake equivalent to \> 4 cups of coffee or \> 6 cups of tea.
* Current or past history of symptomatic orthostatic hypotension or history of vasovagal episode(s).
* Subjects with systolic blood pressure persistently above 140 mmHg and/or diastolic blood pressure persistently above 90 mmHg.
* 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).
* The subject has a history of chronic pain before screening.
* The subject has used any topical steroid in the previous 30 days if, in the opinion of the investigator this is likely to interfere with study assessments.
* The subject has used any topical capsaicin preparations on the forearms in the previous 30 days.
* The subject suffers from eczema, psoriasis or any other acute or chronic dermatological problem if, in the opinion of the investigator this is likely to interfere with study assessments
* The subject suffers from tinnitus, or has done in the past 3 months.
* Suffers from skin infection or inflammation of the forearm, or has other arm skin irregularities that may in the opinion of the investigator interfere with study assessments.
* Needle phobic.
* The subject does not produce an area of allodynia or hyperalgesia to the electrical hyperalgesia model during the screening session.
* The subject is unable to tolerate the electrical hyperalgesia model or threshold tracking, including anxiety or atypical response to the stimulation.
* Any history of suicidal behaviour or any suicidal ideation of type 4 or 5 on the C-SSRS in the last month.
* Poor veins that would be estimated not to be suitable by a physician for repeated cannulation in both arms.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Biogen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Biogen Medical Director

Role: STUDY_DIRECTOR

Biogen

Countries

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United Kingdom

Other Identifiers

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NP111676

Identifier Type: -

Identifier Source: secondary_id

111676

Identifier Type: -

Identifier Source: org_study_id