Gabapentin and Donepezil Combination on Experimental Human Pain Models

NCT01485185 | Completed Phase 1

• 1 other identifier: 115484
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare the effects of gabapentin alone, and gabapentin + donepezil given together in two types of experimental electrical pain tests in up to 48 healthy male subjects (after 24 recruited in the first cohort an interim analysis will be performed). The study is a randomized, double blind, placebo controlled, 3 was cross-over design study with incomplete block design and 4 treatment options. Placebo, gabapentin alone (lower dose and higher dose) or gabapentin (lower dose) with donepezil.

Conditions

Pain, Neuropathic

Keywords

Donepezil; allodynia; Gabapentin; Sural nerve stimulation; Electrical hyperalgesia

Outcome Measures

Primary Outcomes (2)

• Area of pin-prick hyperalgesia

  Change in Area between treatment arms (compared to baseline), measured during the electrical hyperalgesia model using 26 Milli Neuton(mN) von Frey filament

  Change from baseline visit to day 14 of treatment sessions

• Area of touch-evoked allodynia

  Change in Area between treatment arms (compared to baseline), measured during the electrical hyperalgesia model using a cotton bud

  Change from baseline visit to day 14 of treatment sessions

Secondary Outcomes (5)

• Pain threshold

  Change from baseline visit to day 14 of treatment sessions

• Ongoing pain intensity rating

  Change from baseline visit to day 14 of treatment sessions

• Pain Tolerance

  Change from baseline visit to day 14 of treatment sessions

• Pain Temporal Summation

  Change from baseline visit to day 14 of treatment sessions

• Intensity of flare

  Change from baseline visit to day 14 of treatment sessions

Study Arms (4)

Gabapentin lower dose alone

EXPERIMENTAL

low dose

Drug: Gabapentin lower dose

Gabapentin higher dose alone

ACTIVE COMPARATOR

higher dose

Other: Placebo (Dop)

Gabapentin in combination with donepezil

EXPERIMENTAL

Gabapentin lower dose and donepezil

Drug: Donepezil; Drug: Gabapentin higher dose

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo (Gaba)

Interventions

Gabapentin lower dose DRUG

Repeat, oral dose

Gabapentin lower dose alone

Donepezil DRUG

Repeat, oral dose

Gabapentin in combination with donepezil

Placebo (Dop) OTHER

Placebo to donepezil, Repeat, oral dose

Gabapentin higher dose alone

Placebo (Gaba) OTHER

Placebo to gabapentin, Repeat, oral dose

Placebo

Gabapentin higher dose DRUG

Repeat, oral dose

Gabapentin in combination with donepezil

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, at the time of signing the informed consent.
• Body weight ≥ 50 Kilogram (kg) and BMI within the range 18.5-29.9 Killogram per square meter (kg/m2) (inclusive).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, psychiatric history, psychiatric evaluation, laboratory tests and cardiac monitoring.
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1.5x Upper Limit of Normal (ULN)
• QT duration corrected for heart rate by Bazett's formula (QTcB) or QT duration corrected for heart rate by Fridericia's formula (QTcF) \< 450 milli second (msec).

You may not qualify if:

• The subject has either a previous disease or current medical condition, which as judged by the Investigator, may compromise safety or affect the interpretation of efficacy data.
• 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).
• Abnormalities in 12-lead Electrocardiogram (ECG)
• Systolic blood pressure (BP) below 90 or above 160mm Hg, or diastolic blood pressure below 50 or above 100 millimeters of mercury (mmHg).
• History of sensitivity to any of the study medications
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of \>21 units. One unit is equivalent to 8 g of alcohol: a half-pint (\~240 millil litre \[ml\]) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
• A positive pre-study drug/alcohol screen at the screening visit.
• Excessive caffeine drinkers (\~5 or more cups a day) .
• Excessive smokers (\>5 /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 screening, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• Use of any topical steroid or capsaicin preparations in the previous 30 days to screening, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• The subject is needle phobic
• The subject is unable to tolerate the electrical hyperalgesia model or nerve stimulation, including anxiety or atypical response to the stimulation on the training at the screening visit.
• The subject does not produce an area of allodynia or hyperalgesia to the electrical hyperalgesia model during the screening session.
• Subject who, in the investigator/designee's judgement, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any evidence of suicidal ideation on any questionnaires e.g. type 4 or 5 on the C-SSRS in the last 6 months.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 2GG, United Kingdom

Location

Related Publications (1)

• Boyle Y, Fernando D, Kurz H, Miller SR, Zucchetto M, Storey J. The effect of a combination of gabapentin and donepezil in an experimental pain model in healthy volunteers: Results of a randomized controlled trial. Pain. 2014 Dec;155(12):2510-2516. doi: 10.1016/j.pain.2014.09.003. Epub 2014 Sep 10.

  PMID: 25218827 DERIVED

Related Links

• Results for study 115484 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Neuralgia; Hyperalgesia

Interventions

Gabapentin; Donepezil; gamma-Aminobutyric Acid

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins; Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: December 5, 2011
• Study Start: October 11, 2011
• Primary Completion: July 3, 2012
• Study Completion: July 3, 2012
• Last Updated: June 12, 2017

Record last verified: 2017-06

Locations

GB (1)