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Restless Legs SyndromePhase 1NCT01476124

Drug Drug Interaction Study With Gabapentin Enacarbil and Morphine

A Phase 1 study testing GEn 600 mg and Morphine in people with Restless Legs Syndrome, run by XenoPort, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for
Restless Legs Syndrome
What is being tested?
GEn 600 mg and Morphine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
18 participants
Where
1 siteUnited States
Study dates
Aug 2011to Oct 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Austin, Texas, 78744

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
morphine Placebo, GEn 600 mg, Morphine, GEn Placebo
Medical subject headings
Restless Legs Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • morphine PlaceboDrug

    Morphine Placebo

  • GEn 600 mgDrug

    Also called XP13512, GSK1838262

    Gabapentin enacarbil 600 mg

  • MorphineDrug

    morphine extended release 60 mg

  • GEn PlaceboDrug

    Gabapentin enacarbil placebo

Study groups in NCT01476124
Study groupRoleWhat they receive
Regimen AExperimentalMorphine placebo + GEn 600 mg
Receives: Drug: morphine Placebo; Drug: GEn 600 mg
Regimen BExperimentalMorphine Extended release (60 mg) + GEn placebo
Receives: Drug: Morphine; Drug: GEn Placebo
Regimen CExperimentalMorphine Extended release (60mg) + GEn 600 mg
Receives: Drug: GEn 600 mg; Drug: Morphine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetics

    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

    Measured: 7 days

Secondary outcomes (2)

  1. Profile of Pharmacokinetics

    Area under the curve (AUC), Concentration Max (Cmax)

    Measured: predose,1,2,3,4,5,6,7,8,9,10,11,12,14,16,18,20,24,26,and 36 hours post dose

  2. Safety of Patients treated with Gen

    Laboratory safety tests including blood chemistry, urine analysis, ECG testing, and liver enzyme tests

    Measured: Screening to follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2011 (estimated)
  2. Study startAug 2011
  3. Primary completionOct 2011
  4. Study completionOct 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01476124
Sponsor's protocol ID
115720
Status last verified
Nov 2011
First submitted
25 Aug 2011
Last updated
16 Jul 2013
Results posted
No
Data monitoring committee
No

Publications

  • Chen C, Upward J, Arumugham T, Stier B, Davy M. Gabapentin enacarbil and morphine administered in combination versus alone: a double-blind, randomized, pharmacokinetic, and tolerability comparison. Clin Ther. 2015 Feb 1;37(2):349-57. doi: 10.1016/j.clinthera.2014.10.015. Epub 2014 Nov 20.

    PubMed 25467190

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GEn 600 mg and Morphine in people with Restless Legs Syndrome, run by XenoPort, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics (time frame: 7 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01476124, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2013.

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