The purpose of this study is to determine the safety and tolerability of a new drug,
GSK163090, which is being developed for the treatment of depression and anxiety disorders.
- Male and female subjects between the ages of 18 - 65 years with a psychiatric
diagnosis of a MDE associated with MDD according to DSM-IV-TR (296.2/296.3) whose
symptoms are considered mild to moderate and have not been taking antidepressant
medication at the time of screening and for at least 4 weeks prior to randomisation.
- If female, the subject is eligible to enter and participate in this study if she is
not lactating and is of:
1. Non-childbearing potential (i.e., physiologically incapable of becoming
pregnant, including any female who is post-menopausal [defined as one year
without menses for women >45 years of age]); is surgically sterile [via
hysterectomy and/or removal of the ovaries] or,
2. Child-bearing potential, has a negative pregnancy test at both screen and
baseline (prior to investigational product administration), and agrees to
acceptable methods of contraception
- Body weight ≥ 50 kg and body mass index (BMI) between 18.5 - 35.0 kg/m2 inclusive.
- Capable of giving informed consent and can comply with the study requirements and
- Subjects have a HAM-D17 score > 18 and <25 at screening and baseline.
- The subject must be able to read, comprehend and record information.
- Non-smoker or light (< 10 cigarettes per day) smoker.
- Agree to abstain from alcohol for 24 hours prior to the start of dosing until
collection of the final pharmacokinetic sample.
- Subjects whose symptoms of the MDE are better accounted for by another diagnosis.
- As a result of any of the medical interview, physical examination or screening
investigations the physician responsible considers the subject unfit for the study.
- The subject has a history of a drug reaction or other allergy which in the opinion of
the physician responsible contraindicates their participation in the study.
- The subject is currently participating or has participated in a clinical trial with a
new chemical entity or any investigational drug during the previous 2 months. In
addition, the subject has not participated in clinical trials with more than 3 new
chemical entities in the past 12 months.
- The subject has a screening ECG with parameters outside ranges defined in the
- The subject has a pulse rate <45 or >100 bpm and/or a systolic blood pressure >150
and/or <90 and/or a diastolic blood pressure >90 and <50.
- History of long QT syndrome (personal or family) or other cardiac conduction
disorder, or other clinically significant cardiac disease.
- The subject has any liver function test (LFT) elevated >1.5 times above the reference
range at pre-study screening that remain elevated with a repeat LFT.
- Any other clinically significant laboratory abnormality.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John'sWort) 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 sponsor the
medication will not interfere with the study procedures or compromise subject safety.
- Use of monoamine oxidase inhibitors (MAOI) and linezolid (antibiotic) for 1 month
prior to first dose of study medication.
- Abuse of alcohol defined as an average weekly intake of greater than 21 units for
males and 14 units for females or an average daily intake of greater than 3 units for
males and 2 units for females. 1 unit is equivalent to a half-pint (220mL) of beer or
1 (25ml) measure of spirits or 1 glass (125ml) of wine.
- Consumption of grapefruit juice or grapefruit within 7 days prior to the first dose
of study medication until collection of the last PK sample.
- The subject is unable to abstain from strenuous physical activity for 48 h prior to
screening and follow up and for 48 h prior to and 48 h after each treatment period.
- Where participation in study would result in donation of blood in excess of 500 mL
within a 90 day period
- An unwillingness of male subjects to abstain from, or use a condom during, sexual
intercourse with pregnant or lactating women from the time of the first dose of study
medication until 90 days following administration of the last dose of study
- An unwillingness of the male subject to use a condom/spermicide in addition to having
their female partner use another form of contraception such as an IUD, oral
contraceptives, injectable progesterone, subdermal implants or a tubal ligation if
the woman could become pregnant from the time of the first dose of study medication
until 90 days following administration of the last dose of study medication.
- Current or recent (within one year) gastrointestinal disease; a history of
malabsorption, esophageal reflux, irritable bowel syndrome; frequent (more than once
a week) occurrence of heartburn; or any surgical intervention (e.g., cholecystectomy)
which would be expected to influence the absorption of drugs.
- Subjects who, in the investigator's judgement, pose a homicidal or serious suicidal
risk, have made a suicide attempt within 6 months preceding screening or who have
ever been homicidal.
- The subject has a history of a clinically significant abnormality of the neurological
system (including dementia and other cognitive disorders or significant head injury)
or any history of seizure (excluding febrile seizure).
- The subject has tested positive for hepatitis C antibody or hepatitis B surface
- The subject has tested positive for HIV.
- The subject has a past history of drug abuse or dependence according to DSM-IV TR
criteria within the past 12 months or has tested positive for urine drugs of abuse at
- The subject has any history of serotonin syndrome or in the investigator's judgement,
a history of clinical significant intolerance to SSRIs.
- Subjects with a history of migraine headaches that respond to treatment with triptan