This is Phase 2, multicenter, double-blind, parallel-group, placebo-controlled study to evaluate the safety and efficacy of two different doses of new osteoarthritis ointment compared with a placebo ointment applied topically to 1 knee (target knee) for 4 weeks (day 1 through day 28) in patients with primary OA affecting a single knee. For each patient, duration of study participation will be approximately 12 weeks consisting of a 4-week screening period, a 4-week treatment period, and a 4-week follow-up period.
BACKGROUND & RATIONALE
Osteoarthritis (OA) is the most common form of arthritis (http://www.availclinical.com/
Risk factors include obesity, prior knee injury or surgery, and occupational factors such as bending and lifting. Thepain experienced by patients with OA (http://www.availclinical.com/
This experimental osteoarthritis treatment is a novel, potent, voltage-dependent, sodium channel (NaV) blocker being developed for the treatment of patients with various pain indications, including neuropathic and nociceptive pain. Although not previously studied in patients with OA, this topical ointment has been tested in clinical studies and was well tolerated by patients with postherpetic neuralgia (PHN) and erythromelalgia.
The primary objective of the study is to evaluate the efficacy of 4 weeks of topical administration of this experimental ointment compared with placebo for the relief of symptoms of primary OA of the target knee as assessed by the change from baseline (the 5 days prior to randomization [days –5 to –1]) to the last 5 days of treatment (days 24 to 28) in average evening pain intensity upon walking on a flat surface.
Male and female patients meeting all of the following criteria will be eligible to participate in this OA study:
Patient is between 40 and 85 years of age, inclusive, with a body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the screening visit.
Patient has primary OA in a single knee (target knee) confirmed by American College of Rheumatology criteria for diagnosis of OA and radiograph of target knee rated as 2 to 3 on the Kellgren-Lawrence scale as confirmed by a blinded central study radiologist (digital or digitized radiographs within the 6 months prior to screening acceptable).
Symptomatic, primary OA of the knee with pain is present for most days in the previous 3 months before the screening visit.
For patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or other analgesics at the time of the screening visit, the following criteria must be met:
Patient has visual analog scale (VAS) scores ≥40 mm and <90 mm when rating WOMAC Question 1 (pain on walking) in the target knee at the screening visit.
Patient demonstrates a ‘flare’ of pain on walking in the target knee at the baseline visit following a washout of the regular prior OA therapy defined as baseline visit WOMAC Question 1 score ≥50 mm and <90 mm and worsening by at least 5 mm compared with the score at the screening visit.
For patients not taking analgesics at the time of the screening visit, VAS score must be ≥50 mm and <90 mm when rating WOMAC Question 1 in the target knee at the screening and baseline visits.
Patient has an average VAS score of ≥50 mm when rating WOMAC Question 1 in the evening during the 5 days prior to the randomization visit.
Patient has a VAS score of <20 mm when rating WOMAC Question 1 (pain on walking) in the contralateral knee or other joints at the screening and randomization visits.
During the baseline period, patients must properly report pain scores for at least 4 of the 5 daily morning recordings for WOMAC Question 1 only and at least 4 of the 5 daily evening recordings of WOMAC Question 1 (as part of the full WOMAC pain subscale) during the 5 days immediately before the randomization visit.
The patient cannot become pregnant because she is surgically sterile (hysterectomy or tubal ligation) or post-menopausal for at least 6 months. OR
If fertile, the patient is not pregnant and has negative pregnancy tests at both the screening and randomization visits, and agrees to use an acceptable method of contraception (including oral contraceptives, hormone implant, intrauterine device, spermicide with barrier method, surgically sterile male sexual partner[s], or no sexual partners) for the duration of the study.
The patient must agree to use a barrier method of contraception in combination with a spermicide with any female partner unless she cannot become pregnant because she is surgically sterile (hysterectomy or tubal ligation) or post-menopausal for at least 6 months, or she is fertile but using an acceptable method of contraception (ie, oral contraceptives, hormone implant, or intrauterine device).
Patient must sign written informed consent form (ICF) and be willing to comply with all study procedures and restrictions.
Except for OA, patient is judged by the investigator to be medically healthy and able to participate in the study.
*Avail Clinical Research conducts a variety of Clinical Research Studies in Florida (http://www.availclinical.com/