Clinical trial NCT02712957: A Proof-of-Concept Study Assessing NEO6860 in Osteoarthritis Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain
Osteoarthritis of the Knee
Lead sponsor: Neomed Institute
Sponsor class: OTHER
First posted: 2016-03-18
Enrollment: 54
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: 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.
timeFrame: 8 hours post dosing. This endpoint will be collected 3 times, 8 hours post dosing for each period: NEO6860, naproxen and placebo.
Secondary outcomes:
measure: WOMAC 3.1 Index Likert pain subscale
timeFrame: from baseline (screening) to 24 hour recall post 1 day treatment at each of the 3 periods
measure: Patient's Global Impression of Change (PGIC)
timeFrame: 24 hour post 1 day treatment at each of the 3 periods
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Diex Recherche Montreal Inc
state: Quebec
city: Montreal
country: Canada
facility: Algorithme Pharma
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke Inc
state: Quebec
Study officials:
affiliation: Neomed Institute
name: Dan A Chiche, MD
role: STUDY_DIRECTOR
References: