Concentration-QT Study of Paroxetine in Healthy Adults

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:

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: a. Heart rate ≥ 40 beats per minute b. PR interval ≤ 220 milliseconds (msec) (For PR, QRS and QTcF interval, and Q wave, the mean of triplicate ECGs will be used) c. Q waves < 50 msec (For PR, QRS and QTcF interval, and Q wave, the mean of triplicate ECGs will be used) d. QRS interval to be ≥ 60msec and < 120msec (For PR, QRS and QTcF interval, and Q wave, the mean of triplicate ECGs will be used) e. The waveforms must enable the QT interval to be clearly defined f. 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).

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 β-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.