| Eligibility |
Inclusion Criteria:
- Participants, both male and female, aged between 18 to 65 years, at the time of
signing the informed consent.
- Participants determined as healthy based on medical evaluation by an experienced
physician.
- A female participant is eligible to participate if she is of:
- Nonchildbearing potential defined as premenopausal females with a documented
tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrhea.
- Child-bearing potential and agrees to use one of the contraception methods for an
appropriate time as mentioned in the study protocol.
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline
phosphatase, and bilirubin = 1.5x (Upper Limit of Normal) ULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Body weight = 45 kilogram (kg) and Body Mass Index (BMI) within the range 18 to 29.5
kilogram per metre square (kg/m2) (inclusive).
- No significant abnormality on 12-lead Electrocardiogram (ECG) at Screening in supine
position, including the following specific requirements:
1. Heart rate = 40 beats per minute
2. PR interval = 220 milliseconds (msec) (For PR, QRS and QTcF interval, and Q wave,
the mean of triplicate ECGs will be used)
3. Q waves < 50 msec (For PR, QRS and QTcF interval, and Q wave, the mean of
triplicate ECGs will be used)
4. QRS interval to be = 60msec and < 120msec (For PR, QRS and QTcF interval, and Q
wave, the mean of triplicate ECGs will be used)
5. The waveforms must enable the QT interval to be clearly defined
6. QTcF interval must be < 450msec (machine or manual reading).
- A signed and dated written informed consent obtained from participants capable of
giving written informed consent, which includes compliance with the requirements and
restrictions listed in the consent form.
- Non-smokers (never smoked or not smoking for >6 months with <10 pack years history
(Pack years = (cigarettes per day smoked/20) x number of years smoked) or light
smokers (less than 5 cigarettes per day).
Exclusion Criteria:
- History or presence of any medically significant disease that may cause additional
risk or interfere with the study procedures or outcome.
- History of symptomatic arrhythmias.
- History of hypersensitivity to paroxetine and excipients
- History of abnormal coagulation parameters, bleeding disorders or conditions which may
predispose to bleeding.
- History of, or active suicidal ideation. Includes assessment using the Columbia
Suicide Severity Rating Scale (C-SSRS)
- Must not have a pre-diagnosed mood disorder
- Participant is mentally or legally incapacitated.
- A supine blood pressure that is persistently higher than 140/90 millimetres of mercury
(mmHG) at Screening.
- A supine heart rate outside the range 50-90 beats per minute (bpm) at Screening.
- A positive screening Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.
- Current or chronic history of liver disease or known hepatic or biliary abnormalities
(except for Gilbert's syndrome or asymptomatic gallstones).
- A positive drug/alcohol screen at screening or prior to dosing.
- A positive test for Human Immune Virus (HIV) antibody at Screening.
- History of regular alcohol consumption within 6 months of the study defined as: an
average weekly intake of >21 units for males or >14 units for females. One unit is
equivalent to 8 g of alcohol: a half-pint (~240 millilitre [ml]) of beer, 1 glass
(125ml) of wine or 1 (25 ml) measure of spirits.
- The participant has participated in a clinical trial and has received an
investigational product within the following time prior to the first dosing day in the
current study: 3 months, 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 the following medications 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 the
study medication: monoamine oxidase inhibitors (including linezolid), thioridazine,
pimozide, serotonergic drugs (including L-tryptophan, triptans, tramadol, selective
serotonin reuptake inhibitors, lithium and fentanyl, tamoxifen, anti-coagulants,
clozapine, phenothiazines, tricyclic antidepressants, acetylsalicylic acid,
non-steroidal anti-inflammatory drugs, Cox-2 inhibitors, antiarrhythmics, quinolone
antibiotics, macrolides (including clarithromycin and erythromycin), ketoconazole and
itraconazole
- Use of 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.
- No current use of any medication other than paracetamol (doses =2 grams/day).
- Consumption of Seville oranges, pummelos (members of the grapefruit family) or
grapefruit juice from 7 days prior to the first dose of study medication.
- Where participation in the study would result in donation of blood or blood products
more than 500 mL within a 3-month period.
- Pregnant females as determined by positive serum ß-HCG test at screening or serum/
urine beta-Human chorionic gonadotropin (HCG) prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Participants with unsuitable veins for cannulation and repeat venepuncture.
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