Adamas Pharmaceuticals recently reported positive results from its Phase 2 proof-of-concept clinical trial evaluating ADS-5102 (amantadine HCl), an extended-release version of amantadine, in multiple sclerosis (MS) patients with difficulties in walking.
The trial (NCT02471222), a double-blind, placebo-controlled and two-arm parallel group study, evaluated ADS-5102 given once daily at 340 mg, at bedtime, for four weeks to the 60 MS patients enrolled.
Primary outcome measures included the safety of ADS-5102, as assessed by adverse events, safety-related drug discontinuation, vital signs, and laboratory tests. Secondary outcomes looked at measures of walking ability, including the timed 25-foot walk (T25FW), Timed Up and Go, 2 Minute Walk test, and MS Walking Scale-12. Other outcomes assessed disease symptoms, such as Fatigue Scale for Motor and Cognitive Functions, the Beck’s Depression Inventory-2, and the Brief International Cognitive Assessment for MS.
Findings indicated that ADS-5102 is well-tolerated in patients with MS, and has a positive impact on walking speed, with a nearly 15 percent placebo-adjusted improvement seen in the T25FW.
Treatment-related adverse events observed were similar to amantadine’s safety profile. Most trial participants had at least one mild or moderate adverse event (17 in the ADS-5102 treatment arm and 19 in the placebo arm). Five patients discontinued treatment with ADS-5102 due to an adverse event. The most commonly reported adverse events included abnormal dreams, ataxia, constipation, agitation, nausea, dry mouth, insomnia, dehydration, hallucination, fall and pollakiuria (increased urinary frequency).
Adamas is planning to present these Phase 2 findings at a future scientific meeting. The company is also testing ADS-5102 for the treatment of levodopa-induced dyskinesia associated with Parkinson’s disease. (Amantadine, an oral drug that was originally approved by the U.S. Food and Drug Administration (FDA) to treat the influenza A virus, is also used to treat symptoms of Parkinson’s disease.)
“We are excited by these positive MS walking data, which represent our fourth successful controlled clinical trial with ADS-5102,” Gregory T. Went, PhD, chairman and chief executive officer of Adamas Pharmaceuticals, said in a press release. “We are now ready to speak with the FDA about a pivotal registration program for impaired walking in people with MS.”
Adamas specializes in modifying the pharmacokinetic profiles of approved drugs to create new treatments for chronic diseases of the central nervous system, like ADS-5102. “We believe these novel data showing a benefit of ADS-5102 on walking speed in MS patients … further validate the strength of Adamas’ ‘shape matters’ discovery and development platform,” Dr. Went said. “The notion of shape incorporates aspects like timing, the profile and drug level, and how they can be modified to improve the way medicines behave in the body.”
Rajiv Patni, MD, the company’s chief medical officer, added: “We are extremely satisfied with the data as we believe it demonstrates the benefit ADS-5102 may be able to deliver to MS patients with walking impairment. Approximately 75 percent of individuals with MS experience clinically significant walking impairment; these are individuals who could potentially benefit from new medicines.”