We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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:
ClinicalTrials.gov Identifier:
NCT00964288
First Posted: August 24, 2009
Last Update Posted: October 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Biogen
  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
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, 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 Biogen:

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 ]

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 ]
  • To further investigate the safety and tolerability of single oral doses of GSK1014802 [ Time Frame: 16 weeks ]
  • To assess relationships between GSK1014802 pharmacokinetics and pharmacodynamic endpoints. [ Time Frame: 16 weeks ]

Enrollment: 16
Actual Study Start Date: July 31, 2009
Study Completion Date: November 30, 2009
Primary Completion Date: November 30, 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Period 1 Drug: GSK1014802 low dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Placebo
To match GSK drug and positive control
Period 2 Drug: GSK1014802 low dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Placebo
To match GSK drug and positive control
Period 3 Drug: GSK1014802 low dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Placebo
To match GSK drug and positive control
Period 4 Drug: GSK1014802 low dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Lidocaine
positive control
Drug: GSK1014802 high dose
oral tablet
Other Name: BIIB074 and CNV1014802
Drug: Placebo
To match GSK drug and positive control

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.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00964288


Sponsors and Collaborators
Biogen
Investigators
Study Director: Biogen Medical Director Biogen
  More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT00964288     History of Changes
Other Study ID Numbers: 111676
NP111676
First Submitted: July 23, 2009
First Posted: August 24, 2009
Last Update Posted: October 26, 2017
Last Verified: October 2017

Keywords provided by Biogen:
electrical hyperalgesia
threshold tracking
pain

Additional relevant MeSH terms:
Neuralgia
Hyperalgesia
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Somatosensory Disorders
Sensation Disorders
Lidocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action