A clinical study to measure the effects of injection-site cooling on pain experienced after knee injections of capsaicin in healthy subjects and in patients with knee osteoarthritis.

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).