Drug Drug Interaction Study With Gabapentin Enacarbil and Morphine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
XenoPort, Inc.
ClinicalTrials.gov Identifier:
NCT01476124
First received: August 25, 2011
Last updated: July 15, 2013
Last verified: November 2011
  Purpose

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 Intervention Phase
Restless Legs Syndrome
Drug: morphine Placebo
Drug: GEn 600 mg
Drug: Morphine
Drug: GEn Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
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:


Further study details as provided by XenoPort, Inc.:

Primary Outcome Measures:
  • 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:
  • 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 Interventions
Experimental: Regimen A
Morphine placebo + GEn 600 mg
Drug: morphine Placebo
Morphine Placebo
Drug: GEn 600 mg
Gabapentin enacarbil 600 mg
Other Names:
  • XP13512
  • GSK1838262
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
Other Names:
  • XP13512
  • GSK1838262
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 enzyme inducer) or 5 half-lives (whichever is longer) before the first dose of study treatment, unless in the opinion of the investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • Subject has a history of sensitivity to gabapentin, morphine, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates participation in the study
  • Subject's participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period
  • Subject is unwilling or unable to follow the procedures outlined in the protocol
  • Subject has a screening heart rate <45 or >100 bpm, systolic blood pressure >140 or <100 mm Hg, or diastolic blood pressure >90 or <60 mm Hg in the semi supine position and the value(s) do not return to within reference range upon retest.
  • Subject has postural hypotension demonstrated at the screening medical ( defined as a fall in systolic pressure of 30mmHg or more and/or a fall in diastolic pressure of 20mmHg or more after standing for 3 minutes) or a history of clinically significant symptomatic postural hypotension or vaso vagal episodes
  • Subject smokes more than 5 cigarettes or equivalent/day. Subjects should continue their smoking/non-smoking habits throughout the study apart from refraining from smoking on study days
  • Subject has a history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, GI, endocrine, immunologic, dermatologic, neurologic or psychiatric disease
  • Subject has a history of seizures other than febrile seizures as a child
  • Subject has received any medications known to chronically alter drug absorption or elimination processes within 30 days of the first dose administration, in the opinion of the Sponsor or investigator
  • Subject has a creatine kinase value greater than the ULN that is not explainable by recent strenuous exercise and the value does not return to within reference range upon retest.
  • Subject has current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Subject is mentally or legally incapacitated
  • Subject has a history of respiratory depression, acute or severe bronchial asthma, or hypercarbia
  • Subject has or is suspected of having paralytic ileus or chronic constipation
  • Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt
  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: NCT01476124

Locations
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78744
Sponsors and Collaborators
XenoPort, Inc.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: XenoPort, Inc.
ClinicalTrials.gov Identifier: NCT01476124     History of Changes
Other Study ID Numbers: 115720
Study First Received: August 25, 2011
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Restless Legs Syndrome
Nervous System Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Parasomnias
Mental Disorders
Gabapentin
Morphine
Gamma-Aminobutyric Acid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Antiparkinson Agents
Anti-Dyskinesia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on October 19, 2014