Cohort 1 Key Inclusion Criteria:
- Subject is aged between 18 and 45 years, inclusive.
- Subjects Body Mass Index (BMI) is between 18 and 32 kg/m^2, inclusive and subject's weight is greater than or equal to 50 kg.
- Subjects must be in good health, in the opinion of the Investigator, as determined by a medical history, physical examination, clinical laboratory tests, vital signs and 12 lead electrocardiogram (ECG).
Cohort 1 Key Exclusion Criteria:
- Subject has had a clinically significant illness that has not completely resolved in the four weeks before screening.
- Subject has a history of neurological disorder which may impact the perception of pain or impairs the subject's ability to fully participate in the trial.
Cohorts 2-4 Key Inclusion Criteria:
- Subject is aged between 45 and 75 years, inclusive.
- Subject's BMI is between 18 and 32 kg/m^2, inclusive and subject's weight is greater than or equal to 50 kg.
- Subject has a diagnosis of bilateral moderate to severe painful knee OA (subjects will be required to have a score on Pain with walking in the previous 24 hours, of 4 to 9, inclusive NPRS 0-10). The condition must be chronic with a history of painful arthritis for at least 3 months prior to entry in the study.
Cohorts 2-4 Key Exclusion Criteria:
- Subject has had a clinically significant illness, other than osteoarthritis, that has not completely resolved in the four weeks before screening.
- Subject has a history of neurological disorder which may impact the perception of pain or impairs the subject's ability to fully participate in the trial.
- Subject has used analgesic medications in the 2 days prior to dosing, except for paracetamol, as needed.
- Subject has used topical medications applied to the knee for OA pain (including capsaicin, lidocaine, prescription or OTC medications) from 90 days prior to screening through to dosing.
- Subject has been injected with corticosteroids in the knee 90 days prior to screening through to dosing.
- Subject currently uses opioids for any condition other than OA knee pain (maximum dose 15 mg hydrocodone, or equivalent, per day prescribed by a physician).