(2R,6R)-Hydroxynorketamine for the Treatment of Neuropathic Pain

Inclusion Criteria:

• Adult patients (18 to 80 years) with an established diagnosis of chronic (> 3 month)NP of the extremities.

• Presence of NP as determined at screening using the 10 item Neuropathic PainQuestionnaire (DN4), with a score of ≥4 required for study inclusion.

• Ability to read and write English sufficiently to complete study related procedures.

• A body mass index (BMI) (weight [kg]/height[m ]) between 18 and 35 kg/m (inclusive)and weighs between 50 kg and 120 kg (110 - 264 pounds).

• Blood pressure with subject is in a supine position for approximately 5 minutesbetween 90 and 145 mmHg systolic and no higher than 90 mmHg diastolic at baseline.

• A 12-lead ECG with no clinically significant abnormality as judged by theInvestigator and QTc interval ≤ 450 milliseconds at baseline.

• Resting pulse rate between 45 and 100 beats per minute.

• Clinical laboratory findings and liver function tests within the normal range, or ifoutside of the normal ranges, deemed not clinically significant in the opinion ofthe PI.

• Agree to provide written informed consent and comply with the rules regardingconsumption of alcohol, caffeinated beverages, and tobacco/nicotine products duringthe study.

• Patients may be taking scheduled or as needed medications for their chronicneuropathic pain and agree to continue taking the scheduled medications throughoutthe study period.

• If the subject experiences pain relief they may elect not to take as neededmedications.

Exclusion Criteria:

• Subjects with suspected increased intracranial or intraocular pressure.

• Subjects that have previously received ketamine for the treatment of a chronic paindiagnoses.

• Previous or current participation in any clinical study with an investigationaldrug, device, or biologic within 30 days.

• Subjects with severe medical illness including (but not limited to) hepatic,cardiovascular, pulmonary, renal, hematologic, endocrine, gastrointestinal,immunologic, dermatologic, neurologic, oncologic, or psychiatric disease that in theopinion of the PI would endanger the safety of the subject or the validity of thestudy results.

• Clinically significant acute illness in the 2 weeks prior to dosing.

• Inability to effectively communicate with research staff.

• Subjects with known liver disease.

• Widespread pain or a diagnosis of fibromyalgia.

• Current diagnosis of mental illness.

• Pregnancy.

• Allergy to ketamine or any study drug.

• Consumption of beverages or food that contain alcohol, grapefruit, poppy seeds,Brussel sprouts, pomegranate, broccoli, char-grilled meat within 2 days prior todrug administration.

• Use of tobacco or nicotine-containing products within 4 weeks prior to drugadministration.

• Poor peripheral venous access.

• Subjects in the opinion of the PI should not participate in the study.