Drug Drug Interaction Study With Gabapentin Enacarbil and Morphine

This study has been completed.

First Received on August 25, 2011.  
Last Updated on November 17, 2011  
History of Changes
This Clinical Trial Sponsored By: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01476124
 

Purpose for Clinical Trial

This double-blind study will evaluate the pharmacokinetics of a single dose of morphine or gabapentin derived from gabapentin enacarbil (GEn) after administration of morphine and GEn alone and in combination as well as the tolerability of morphine administered with GEn. The dose of GEn will be 600 mg administered with food. Morphine/morphine placebo will be administered 2 hours prior to GEn/GEn placebo in the fasted state. A 60 mg dose of a controlled release formulation of morphine will be given. Blood samples for evaluation of gabapentin, morphine and morphine-6-glucuronide will be collected. The pharmacodynamic effect of co-administering both treatments will be assessed using visual analog scales for somnolence/sedation, dizziness and nausea.

Condition Study Intervention Clinical Trial Phase
Restless Legs Syndrome Drug: morphine Placebo
Drug: GEn 600 mg
Drug: Morphine
Drug: GEn Placebo
Phase 1

Study Type: Study Interventional
Study Design: Allocation: Randomized
Study Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, 3-Part Crossover Study to Assess the Pharmacokinetics and Tolerability of Single Doses of Gabapentin Enacarbil and Morphine Administered Alone and in Combination in Healthy Subjects

Resource links provided by NLM:

MedlinePlus related topics:
Restless Legs
Drug Information available for:
Morphine sulfate
Gabapentin
Gabapentin enacarbil

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures For Clinical Trial:

  • Pharmacokinetics [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    evaluate the pharmacokinetics of morphine, morphine-6-glucuronide and of gabapentin derived from GEn following administration of single doses of morphine (60 mg) and GEn (600 mg) alone and in combination

Secondary Outcome Measures For Clinical Trial:

  • Profile of Pharmacokinetics [ Time Frame: predose,1,2,3,4,5,6,7,8,9,10,11,12,14,16,18,20,24,26,and 36 hours post dose ] [ Designated as safety issue: No ]
    Area under the curve (AUC), Concentration Max (Cmax)

  • Safety of Patients treated with Gen [ Time Frame: Screening to follow-up ] [ Designated as safety issue: Yes ]
    Laboratory safety tests including blood chemistry, urine analysis, ECG testing, and liver enzyme tests

Enrollment: 18
Study Start Date: August 2011
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Experimental: Regimen A

Morphine placebo + GEn 600 mg
Drug: morphine Placebo

Morphine Placebo

Drug: GEn 600 mg

Gabapentin enacarbil 600 mg
Experimental: Regimen B

Morphine Extended release (60 mg) + GEn placebo
Drug: Morphine

morphine extended release 60 mg

Drug: GEn Placebo

Gabapentin enacarbil placebo
Experimental: Regimen C

Morphine Extended release (60mg) + GEn 600 mg
Drug: GEn 600 mg

Gabapentin enacarbil 600 mg

Drug: Morphine

morphine extended release 60 mg

Detailed Description:

This double-blind study will evaluate the pharmacokinetics of a single dose of morphine or gabapentin derived from gabapentin enacarbil (GEn) after administration of morphine and GEn alone and in combination as well as the tolerability of morphine administered with GEn. The dose of GEn will be 600 mg administered with food. Morphine/morphine placebo will be administered 2 hours prior to GEn/GEn placebo in the fasted state. A 60 mg dose of a controlled release formulation of morphine will be given. Blood samples for evaluation of gabapentin, morphine and morphine-6-glucuronide will be collected. The pharmacodynamic effect of co-administering both treatments will be assessed using visual analog scales for somnolence/sedation, dizziness and nausea.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject is healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, clinical laboratory tests, and 12 lead ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
  • Subject is a male between 18 and 65 years of age inclusive, at the time of signing the informed consent
  • Subject has a body weight >55 kg and body mass index (BMI) within the range of 19 to 30 kg/m2 (inclusive)
  • Subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form
  • Subject has a QTcB <450 ms
  • Subject has a creatinine clearance (CrCl) >80 mL/min. The CrCl is estimated using the Cockcroft and Gault equation. Details on CrCl calculations are provided in the Study Procedures Manual (SPM)
  • Subject has an aspartate aminotransferase (AST), ALT, and alkaline phosphatase within reference range at the screening visit. Isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35% of the total bilirubin

Exclusion Criteria:

  • Subject has positive prestudy drug or alcohol screen results. At minimum, the drug screen will include alcohol, cotinine, amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines
  • Subject has positive prestudy (within 3 months of Screening) hepatitis B surface antigen or positive hepatitis C antibody results
  • Subject has a positive prestudy human immunodeficiency virus (HIV) antibody result
  • Subject has a history of regular alcohol consumption within 6 months of the study defined as: an average intake of >14 drinks/week . One drink is equivalent to (12 g of alcohol) = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits.
  • Subject has participated in a clinical trial and has received an investigational product within the following time period before the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
  • Subject has been exposed to more than 4 new chemical entities within 12 months before the first dosing day
  • Subject has used prescription or nonprescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzy

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