Arbaclofen extended-release (ER) tablets taken twice a day can effectively reduce spasticity (muscle stiffness) in patients with multiple sclerosis (MS) with similar potency to that of standard and more-frequently-dosed baclofen (brand name Lioresal), Phase 3 clinical trials show.
Latest trial data were presented in two posters during the 33rd Annual Meeting of the Consortium of Multiple Sclerosis Centers that was held in Seattle, Washington.
Approximately 60–90% of MS patients experience spasticity, a symptom characterized by uncontrolled stiffness and contraction of muscles. Spasticity can be mild or severe, causing painful spasms, and being a main cause of morbidity in these patients. To prevent the deterioration of knees, shoulders, ankles, elbows, and hips, appropriate treatment is necessary.
Spasticity is frequently treated with baclofen (among other names), an approved therapy available in different forms that acts as a muscle relaxant and an anti-spastic agent. However, its therapeutic doses may cause unwanted side effects in the central nervous system, which affect patients’ adherence to the treatment.
Arbaclofen ER tablets (brand name Ontinua), developed by Osmotica Pharmaceuticals, distributes the therapy’s active ingredients over time in the patient’s body, allowing for less-frequent dosing and likely decreasing the risk of systemic adverse side effects.
Researchers conducted a Phase 3 clinical trial (identified as OS440-3002, NCT01743651) across several clinical centers in the U.S., Russia, and Ukraine to compare the effectiveness and safety of arbaclofen ER with baclofen in patients with spasticity due to MS.
The study included 341 MS patients, the majority having relapsing-remitting (57.5%) or secondary progressive MS (38.4%), followed by 2.6% with primary progressive MS, and 0.9% who had progressive-relapsing MS.
Participants were randomized into three groups to receive two daily doses of 20 mg of arbaclofen ER, the same dose of baclofen given four times a day, or a placebo. Each therapy was given at increasing doses over two weeks, followed by 12 weeks of maintenance treatment.
The study’s main goal was to assess the changes in muscle tone and spasticity using the total numeric-transformed Modified Ashworth Scale for the most affected limb (TNmAS-MAL); improvements in patients clinical status was assessed by the Clinician Global Impression of Change (CGIC) at the end of the maintenance treatment.
Results showed that patients treated with arbaclofen ER had a significantly more pronounced reduction in the TNmAS-MAL compared to the placebo-treated patients, along with a significantly higher improvement in the CGIC. Changes in the 88-item Multiple Sclerosis Spasticity Scale (MSSS-88) also were more significant in the arbaclofen group than in the placebo group.
Researchers saw no differences between the standard baclofen treatment and arbaclofen ER for either of the two primary goals.
In addition, drowsiness and dizziness were less frequent in patients treated with arbaclofen ER than in those who took baclofen. Treatment-emergent side effects were reported by 57.3%, 72.6%, and 50% of patients in the arbaclofen ER, baclofen, and placebo group, respectively. The most common side effects were drowsiness, lack of energy, and muscle weakness.
Overall, these results suggest that “twice-daily arbaclofen ER was efficacious and well-tolerated in subjects with spasticity,” researchers wrote.
These results were shared at CMSC annual meeting in the poster “Arbaclofen Extended-Release Tablets Versus Placebo or Baclofen for the Treatment of Spasticity in Subjects with Multiple Sclerosis (Study OS440-3002).”
In a second Phase 3 study (identified as OS440-3003, NCT01844232), researchers tested the safety of arbaclofen ER when given at a 20 mg dose twice daily for more than a year. The trial enrolled 182 patients (average age 48 years), of which 27 had participated in the previous OS440-3002 study. The remaining participants had never been treated with arbaclofen ER.
Each group of patients has had spasticity for 12 and seven years, respectively. After one year of treatment, the dose of arbaclofen ER was gradually reduced.
In total, 148 patients (80.4%) reported treatment-emergent side effects, with the most common including muscle weakness (24 participants) and urinary tract infection (21 patients). Additional side effects, although less frequent, included drowsiness, dizziness, pollakiuria (increased daytime urinary frequency), and lack of energy.
There were no deaths reported during the study duration, and episodes of delirium were the only side effect likely linked to treatment with arbaclofen ER.
“Arbaclofen ER administered twice daily was safe and well tolerated in patients with MS-related spasticity. A reduction in spasticity, as measured by TNmAS-MAL, was maintained throughout the treatment period,” researchers wrote.
That safety data was presented in the poster titled, “One-Year Study to Evaluate the Long-Term Safety of Arbaclofen Extended-Release Tablets in Multiple Sclerosis–Related Spasticity (Study OS440-3003).”