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

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

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

Study Overview

• Status: Completed
• Conditions: Pain; Osteoarthritis of the Knee
• Intervention / Treatment: Drug: NEO6860; Drug: Naproxen placebo; Drug: NEO6860 placebo; Drug: Naproxen

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2Y 1S1
      • DIEX Recherche Montreal Inc
    • Montreal, Quebec, Canada, H3P 3P1
      • Algorithme Pharma
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Diex Recherche Sherbrooke Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NEO6860; 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; TRPV1 antagonist; Drug: Naproxen placebo; inactive substance
PLACEBO_COMPARATOR: Placebo; In this arm, patients will receive both placebo: oral liquid suspension (NEO6860 placebo) and capsule (naproxen placebo).	Drug: Naproxen placebo; inactive substance; Drug: NEO6860 placebo; Inactive substance
ACTIVE_COMPARATOR: Naproxen; 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; Inactive substance; Drug: Naproxen; NSAID

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Neomed Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): November 17, 2016
• Study Completion (ACTUAL): November 24, 2016

Study Registration Dates

• First Submitted: March 9, 2016
• First Submitted That Met QC Criteria: March 14, 2016
• First Posted (ESTIMATE): March 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2017
• Last Update Submitted That Met QC Criteria: March 10, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Naproxen
• Other Study ID Numbers: NEO6860-OA-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO