Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine

This is a double-blind, vehicle-controlled study to evaluate the antipruritic efficacy of
topical ketamine, amitriptyline, lidocaine, and a tri-combination of ketamine, amitriptyline
and lidocaine (hereafter referred to as "KeAmLi") using non-histaminergic itch provocations
in healthy volunteers. Each participant will be pre-treated with the vehicle and 4 active
topical creams, over two study visits (3 treatments on the 1st visit and 2 treatment on the
2nd visit). Each treatment will be applied to the randomized forearm test area for 30 minute,
and then sensory testing will be performed. Sensory testing includes thermal and mechanical
stimuli, and itch induction using the plant cowhage. These tests will reveal mechanistic
information and potential cellular and molecular targets for improved antipruritic and
analgesic therapies.

Inclusion Criteria:

1. Healthy subjects (absence of disease) between 18 and 50 years of age.

2. Must be in general good health with no disease or physical conditions that would
impair evaluation of itch and pain perception.

3. No history of chronic itch or pain.

4. Must abstain from the use of any systemic or topical anti-histamine, steroid, or pain
relief medications 48 hours prior to the study visits.

5. Must abstain from the use of moisturizers on the arms the day of study visit.

Exclusion Criteria:

1. Individuals under 18 or over 50 years of age.

2. Inability to complete the required measures.

3. The presence of an itchy skin disease or a painful condition.

4. Diagnosis of diseased that would affect itch or pain perception (e.g. neuropathies).

5. Currently enrolled in any investigational study in which the subject is receiving any
type of drug, biological, or non-drug therapy.

6. Use of oral, topical analgesics, or other medications known to interfere with itch or
pain perception 48 hours prior to the study visits (e.g. antihistamines, anesthetics,
anti-inflammatories, opioids, neuroleptics, etc.).

7. Use of emollients on the volar aspects of the forearms arms on the day of the study
visit.

8. Use of anti-depressants, anti-psychotics, and illicit drugs.

9. Known history of neuropathy, uremia, uncontrolled thyroid disease, and diabetes
mellitus.

10. Known history of anaphylactic shock, or allergy to cowhage and/or known adverse
reactions to lidocaine (or other local anesthetics of the amide type), ketamine or
amitriptyline.