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

This study has been terminated.
(During treatment session 3, a subject had a pattern of AEs of severe intensity, suggestive of brainstem toxicity/encephalopathy during lidocaine/saline infusion)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00964288
First received: July 23, 2009
Last updated: July 5, 2012
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Pain, Neuropathic
Neuropathic Pain
Drug: GSK1014802 low dose
Drug: Lidocaine
Drug: GSK1014802 high dose
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind, Double Dummy, Placebo Controlled Cross Over Study With a Positive Control to Investigate the Effect of a GSK Drug on Electrical Hyperalgesia and Threshold Tracking in Healthy Subjects

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To determine the effect of single oral doses of GSK1014802 on area of flare evoked by cutaneous electrical stimulation. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the effect of single oral doses of GSK1014802 and a single i.v. infusion of lidocaine on tests of nerve excitability [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • To further investigate the safety and tolerability of single oral doses of GSK1014802 [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • To assess relationships between GSK1014802 pharmacokinetics and pharmacodynamic endpoints. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: July 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Period 1 Drug: GSK1014802 low dose
oral tablet
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Drug: Placebo
To match GSK drug and positive control
Period 2 Drug: GSK1014802 low dose
oral tablet
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Drug: Placebo
To match GSK drug and positive control
Period 3 Drug: GSK1014802 low dose
oral tablet
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Drug: Placebo
To match GSK drug and positive control
Period 4 Drug: GSK1014802 low dose
oral tablet
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Drug: Placebo
To match GSK drug and positive control

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  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: NCT00964288

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

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00964288     History of Changes
Other Study ID Numbers: 111676
Study First Received: July 23, 2009
Last Updated: July 5, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: NRES Head Office, National Patient Safety Agency

Keywords provided by GlaxoSmithKline:
electrical hyperalgesia
threshold tracking
pain

Additional relevant MeSH terms:
Hyperalgesia
Neuralgia
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Diseases
Pain
Peripheral Nervous System Diseases
Sensation Disorders
Signs and Symptoms
Somatosensory Disorders

ClinicalTrials.gov processed this record on October 23, 2014