A Proof-of-Concept Study Assessing NEO6860 in Osteoarthritis Pain

Study Overview
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Brief Summary
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The purpose of this study is to assess NEO6860, a modality selective TRPV1 antagonist, in patients with pain associated with osteoarthritis of the knee.

Detailed Description
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The study will be randomized, double blind, placebo and active control, a 3-way, 3-period crossover design, where each of the estimated 50 enrolled patients will receive alternately (i) NEO6860 (500 mg bid), (ii) placebo and (iii) Naproxen (500 mg bid). To ensure blinding, double dummy techniques will be used, so that at each period, patient will receive an oral liquid suspension (NEO6860 or its placebo) and one capsule (naproxen or its placebo). Following a screening period, a maximum of 28 days before dosing, subjects will be randomized to one of the scheduled sequences. At each dosing period, subjects will be requested to participate in 2 clinic visits: One residential visit, the morning of investigational product dosing. Subjects will stay in the Clinical Research Unit approximately 13 hours One end of period visit, 24 h after first dosing A total of 2 washout periods of 1 to 3 weeks will separate the dosing periods. Once the 3 dosing periods will be completed, the subjects will come back to the clinic for a follow up visit (7 to 10 days post last dose). Note: for a subpopulation, at one site, an assessment of heat pain threshold and tolerance will be conducted requiring a residential period of approximately 24 hours.

Official Title
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A Proof-of-Concept, Randomized, Double Blind, Placebo and Active Control, 3-Period, Crossover Design Study Assessing NEO6860 in Patients With Pain Associated With Osteoarthritis of the Knee

Conditions
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Pain, Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: NEO6860
* Drug: NEO6860 placebo
* Drug: Naproxen
* Drug: Naproxen placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) between 18.0 and 35.0 kg/m2 inclusive; Patients diagnosed with osteoarthritis of the knee, according to American College of Rheumatology (ACR) guidelines, by meeting at least 3 of the following: age > 50, morning stiffness < 30 minutes, crepitus on active motion, bone tenderness, bone enlargement, no palpable warmth of synovium; Grade I, II or III using Kellgren-Lawrence classification on an X-Ray of the knee WOMAC pain subscale ≥ 8 R square of the Focused Analgesia Selection Task (FAST) outcome value greater than 0.70 Exclusion Criteria: Patients with, or with a history of, any clinically significant disorders (including fibromyalgia and other painful disorders) which may interfere with the primary objectives of the study Patients treated in the previous 3 months with topical capsaicin or intra-articular corticosteroids; Patients with a contra-indication for the use of Naproxen or acetaminophen;

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEO6860<br>NEO6860 is provided as a powder in individual containers to be reconstituted as a suspension. In this arm patients will receive both NEO6860 and a placebo of naproxen. | Drug: NEO6860<br>* TRPV1 antagonist<br>Drug: Naproxen placebo<br>* inactive substance<br>|
| Placebo Comparator: Placebo<br>In this arm, patients will receive both placebo: oral liquid suspension (NEO6860 placebo) and capsule (naproxen placebo). | Drug: NEO6860 placebo<br>* Inactive substance<br>Drug: Naproxen placebo<br>* inactive substance<br>|
| Active Comparator: Naproxen<br>Naproxen is provided as over-encapsulated tablets using a commercially approved medication. In this arm patients will receive both naproxen and a placebo of NEO6860. | Drug: NEO6860 placebo<br>* Inactive substance<br>Drug: Naproxen<br>* NSAID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in Numerical Rating Scale (NRS, 0-10) from baseline after the staircase test to 8 hours post first dose after the staircase test on the index knee. | Patients are asked to step fully up onto a 8-inch (20 cm) high platform with both feet and back down a total of 24 times. | 8 hours post dosing. This endpoint will be collected 3 times, 8 hours post dosing for each period: NEO6860, naproxen and placebo. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC 3.1 Index Likert pain subscale |  | from baseline (screening) to 24 hour recall post 1 day treatment at each of the 3 periods | 
| Patient's Global Impression of Change (PGIC) |  | 24 hour post 1 day treatment at each of the 3 periods |