Study to Assess the Effect of Gabapentin Enacarbil on Simulated Driving in Healthy Subjects

Sponsor

XenoPort, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01411124

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a double-blind, placebo-and active-controlled 3-period crossover study designed to assess the effect of GEn 600 mg on simulated driving performance in healthy volunteers.

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome (RLS)	Drug: gabapentin enacarbil Drug: diphenhydramine Drug: placebo	Phase 1

Detailed Description

proportional systemic gabapentin exposure over a wide dose range. This is a double-blind, placebo-and active-controlled 3-period crossover study designed to assess the effect of GEn 600 mg on simulated driving performance. Subjects will receive each of 3 treatments in a randomized order: GEn 600 mg, placebo and placebo/diphenhydramine 50 mg. Each treatment period will consist of 6 days, with subjects being dosed at approximately 5 pm on each dosing day. The placebo /diphenhydramine treatment will consist of placebo on Days 1-4 and 6 and 50 mg diphenhydramine on Day 5. Placebo will be administered on Day 6 in all treatment periods to ensure washout of drug prior to the start of the next treatment period. Simulated driving performance will be assessed at baseline (prior to randomization) and on Day 5 in the evening (7-9 pm) and on Day 6 between7-9 am and between 11am-1pm for each treatment period.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Active- and Placebo-Controlled, Crossover Study Assessing the Effect of 600 mg Gabapentin Enacarbil on Simulated Driving in Healthy Subjects

Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Oct 1, 2011

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gabapentin Enacarbil 600 mg of Gabapentin Enacarbil	Drug: gabapentin enacarbil 600 mg investigational compound Other Names: XP13512 GSK1838262 Drug: placebo placebo
Active Comparator: diphenhydramine 50 mg	Drug: diphenhydramine 50 mg active comparator Drug: placebo placebo
Placebo Comparator: placebo placebo to match	Drug: placebo placebo

Arm

Intervention/Treatment

Experimental: Gabapentin Enacarbil

600 mg of Gabapentin Enacarbil

Drug: gabapentin enacarbil

600 mg investigational compound

Other Names:

XP13512

GSK1838262

Drug: placebo

placebo

Active Comparator: diphenhydramine

50 mg

Drug: diphenhydramine

50 mg active comparator

Drug: placebo

placebo

Placebo Comparator: placebo

placebo to match

Drug: placebo

placebo

Outcome Measures

Primary Outcome Measures

Lane performance Variability [From Day-1 baseline to end of treatment. Participants will be followed for the duration of the clinic visit an average of 3 weeks.]
change from baseline in lane position variability

Secondary Outcome Measures

Change in Speed Variability [from baseline to end of treatment Participants will be followed for the duration of the clinic visit an average of 3 weeks]
Change from baseline in speed variability
number of simulated crashes [on Days 5 and 6. The subjects will be followed for the duration of the clinic visit an average of 3 week]
number of simulated crashes
Visual Analog Scale [Baseline to end of treatment. The subjects will be followed for the duration of the clinic visit an average of 3 weeks]
Pre driving alterness measured by the Visual analog scale
Visual analog scale on post driving alertness [baseline to days 5 and 6. The subjects will be followed for the duration of the clinic visit an average of 3 weeks]
Post driving alterness measured by visual alterness scale
Visual Analog scale of the difference between pre and post driving alertness [baseline to days 5 and 6. The subjects will be followed for the duration of the clinic visit an average of 3 weeks]
difference between pre and post driving alertness
Incidents of Adverse events [baseline to end of study. The subjects will be followed for the duration of the clinic visit an average of 3 weeks]
safety and tolerability from baseline to end of study
Plasma concentrations of gabapentin [Day 5. The subjects will be followed for the duration of the clinic visit an average of 3 weeks]
Plasma concentration of gabapentin on completion of driving test

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 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
Male or female between 18 and 65 years of age, at the time of signing the informed consent.
A female subject is eligible to participate if she is of Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation at least 6 months previously or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol < 40 pg/mL (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow-up visit is completed.
Body weight > 50 kg and Body Mass Index (BMI) within the range 19 - 30 kg/m2 (inclusive)
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
QTcB < 450 msec
Creatinine clearance (CrCl) >80 mL/min. CrCl is estimated using the equation of Cockcroft and Gault. See study procedure manual for details on creatinine clearance calculations.
AST, ALT, alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
Currently a licensed, experienced driver who drives at least 3 times a week for the past 3 years and with visual acuity assessed by the investigator as being adequate for driving
Able to complete a 1 hour simulated driving test and demonstrate satisfactory driving skills at screening

Exclusion Criteria:

The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
A positive test for HIV antibody
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks/week for men or >7 drinks/week for women. One drink is equivalent to (12 g 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.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to 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).
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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety
History of sensitivity to gabapentin, DPH 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
Pregnant females as determined by positive serum human chorionic gonadotrophin (hCG) test at screening or prior to dosing
Lactating females
Unwillingness or inability to follow the procedures outlined in the protocol
The subject has a screening heart rate <50 or >100 bpm or a systolic blood pressure

140 or <100 mmHg or a diastolic blood pressure >90 or <60 mmHg in the semi-supine position after at least 3 minutes of rest.

Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening
History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease
History of seizures other than febrile seizures as a child
Subjects who have 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
Subjects with a creatine kinase (CK) value of greater than the upper limit of normal that is not explainable by recent strenuous exercise and the value does not return within normal range upon retest
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
Subjects with a sleep disorder e.g. sleep apnea, narcolepsy or primary insomnia
Shift workers who are not on normal day/night sleep cycles
Subjects with a history of closed angle glaucoma, urinary retention or other conditions for which DPH is contra-indicated
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
Subjects who have consumed an average of > 5 cups of caffeinated beverages per day within 20 days of the screening visit