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.
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
