A low-dose (5 or 10 mg) formulation of the nonsteroidal anti-inflammatory drug (NSAID) meloxicam achieved significantly greater pain relief than placebo in patients with osteoarthritis (OA), according to results of a Phase III study presented at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology.
Osteoarthritis of the knee and hip are common causes of pain, affecting approximately 40 million people in the United States. Inadequate pain control can impair patients’ ability to function in the workplace and at home. Although non-NSAIDs can provide effective pain control and are commonly used to treat OA pain, their long-term use is associated with serious dose-related adverse gastrointestinal (GI) and cardiovascular effects. Thus, the European Medicines Agency (EMA) and the FDA have advocated using the lowest effective dose of NSAID for the shortest duration to treat OA pain and other painful conditions.
A response to the EMA and FDA recommendation, Solumatrix meloxicam (Iroko Pharmaceuticals) provides 30% less active ingredient compared with its parent compound using a unique process called SoluMatrix Fine Particle Technology.
“Osteoarthritis is one of the most common causes of disability, and inadequate pain control can lead to joint stiffness that may impair mobility,” said lead author of the study, Roy Altman, MD, professor of medicine in Rheumatology at the Geffen School of Medicine, UCLA, in Los Angeles. “Clinicians have an urgent need for new osteoarthritis treatments that can offer reduced systemic exposure when taken over a long period of time, while also helping to restore some of the loss of function due to the nature of this chronic condition. These data show SoluMatrix meloxicam represents an important new step forward in fulfilling the unmet need for effective low-dose treatment options for osteoarthritis.”
In an interview, Dr. Altman explained that the new technology creates smaller molecules of active drug leading to more rapid and complete absorption. “Hopefully this will lead to fewer GI and other side effects,” he noted.
The 12-week, multicenter, randomized double-blind, double-dummy, fixed-dose, parallel-group, placebo-controlled Phase III study was designed to compare two doses of low-dose meloxicam with placebo on several measures of pain efficacy. The study randomized 403 patients aged 40 and older with a clinical diagnosis of OA of the knee or hip to once-daily SoluMatrix meloxicam 5 mg, once-daily SoluMatrix meloxicam 10 mg or placebo. Mean change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score at week 12 was the primary end point of the study. Secondary efficacy end points included the Patient Global Impression of Change (PGIC), a patient reported outcome measure, as well as the amount of rescue medication (acetaminophen) used by each patient.
At week 12, patients treated with SoluMatrix meloxicam 5 (P=0.0005) and 10 mg (P=0.0059) achieved significantly greater pain relief as measured by the WOMAC pain subscale score than did patients receiving placebo.
Based on self-reported results on PGIC, significantly more patients said that their OA was “very much improved” or “much improved” versus “much worse” or “very much worse” following SoluMatrix meloxicam 5 (P= 0.0049) or 10 mg (P=0.0012) treatment compared with placebo.
Patients in the SoluMatrix meloxicam 5 (P=0.006) and 10 mg (P=0.0013) treatment groups used significantly less rescue medication than patients in the placebo group.
Diarrhea, headache and nausea were the most frequently reported adverse events (occurring in >2% of patients) in patients treated with SoluMatrix® meloxicam.
Dr. Altman said that 12 weeks was a sufficient time to demonstrate efficacy for a formulation of an already FDA-approved drug. Iroko Pharmaceuticals plans to study more patients over longer periods of time, and the study reported at EULAR is a “first step,” he said.
Mark C. Fisher, MD, a rheumatologist at Massachusetts General Hospital, Boston, said that the new lower-dose NSAID might have some plusses for patients.
“There is certainly an element of ‘me too’ to this formulation, but meloxicam has some benefit as it taken once daily, and may be more gentle on the stomach,” he said in an interview. “Having lower doses as options for our patients is certainly beneficial, as the lowest necessary dose is preferred to decrease cardiac, GI and renal toxicity.”