The randomized, double-blind, placebo-controlled study, known as "EASE LID 3," is planned to enroll approximately 70 patients with LID. The 13-week study will include an estimated 35 sites in the US and Europe. Participants will receive 340 mg of ADS-5102 or placebo daily.
The primary endpoint of EASE LID 3 is a reduction in dyskinesia assessed by changes in the Unified Dyskinesia Rating Scale (UDysRS). Additional supporting data will be obtained from the secondary endpoints, including changes in "ON" time without troublesome dyskinesia, "OFF" time, and the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and sub scores.
EASE LID 3 is one of three ongoing clinical trials for the treatment of LID in individuals with Parkinson’s disease. The complete company-sponsored program includes:
- EASE LID 3, a Phase 3 study (described above), which is estimated to enroll approximately 70 patients. The 13-week multi-center, randomized, double-blind, placebo-controlled study will assess the efficacy of a 340 mg dose of ADS-5102 administered once daily at bedtime.
- EASE LID, a Phase 3 trial, which is planned to enroll approximately 130 patients. The 26-week multi-center, randomized, double-blind, placebo-controlled trial will assess the efficacy of a 340 mg dose of ADS-5102 administered once daily at bedtime. The primary endpoint of EASE LID is a reduction in dyskinesia assessed by changes in UDysRS.
- EASE LID 2, a Phase 3 open-label safety study of ADS-5102 in Parkinson’s disease patients with LID.
- EASED, a Phase 2/3 study that enrolled 83 patients. The 8-week, multi-center, randomized, double-blind, placebo-controlled trial assessed the efficacy of three dose levels of ADS-5102 administered once daily at bedtime. The study met its primary endpoint, which was a reduction in dyskinesia assessed by changes in UDysRS.
"Together these trials are expected to generate a comprehensive data set that will support the submission of a New Drug Application (NDA) using ADS-5102 for the treatment of LID," said Natalie McClure, Senior Vice President of Product Development. "We anticipate completing enrollment in all of these studies in 2015, enabling us to achieve a planned NDA submission in 2016."
Adamas’ most advanced wholly owned product candidate is ADS-5102 (amantadine HCl), a high dose, controlled-release version of amantadine that is administered once daily at bedtime. ADS-5102 is designed to address many of the limitations of immediate-release amantadine. Adamas is initially developing ADS-5102 for the treatment of levodopa-induced dyskinesia, or LID, in patients with Parkinson’s disease. LID is a movement disorder that frequently occurs in patients after long-term treatment with levodopa, the most widely used drug for Parkinson’s disease. There are no approved drugs for the treatment of LID in the United States or Europe.
Derived from Adamas’ clinical study data, for patients taking ADS-5102, the amantadine plasma concentration achieved from the early morning through mid-day was approximately two-times that reached following administration of immediate-release amantadine, providing symptomatic relief to patients as they engaged in their daily activities. Further, there were no changes in sleep patterns, a common concern for Parkinson’s disease patients taking immediate-release amantadine.
Parkinson’s disease is a chronic, progressive motor disorder that causes tremors, rigidity, slowed movements and postural instability. The most commonly prescribed treatments for Parkinson’s disease are levodopa-based therapies. In the body, levodopa is converted to dopamine to replace the dopamine loss caused by the disease. Patients initially receive relief from symptoms of Parkinson’s disease for much of the day; this period of relief is known as "ON" time. As the effects of levodopa wear off, the symptoms of Parkinson’s disease return; this is known as "OFF" time. By properly managing the timing of levodopa administration, patients with early-stage Parkinson’s disease can largely avoid "OFF" time during the day.
Over time, as Parkinson’s disease progresses, most patients require increasing doses of levodopa to achieve equivalent therapeutic benefit. Even with increased doses of levodopa, patients may begin to exhibit unpredictable "OFF" episodes throughout the day. In the later stages of the disease, many patients will suffer from LID, a condition characterized by involuntary movements without purpose. LID can become severely disabling, rendering patients unable to perform routine daily tasks. As Parkinson’s disease advances, the symptoms of LID worsen in frequency and severity. Eventually the total time that a patient spends either "OFF" or "ON" with LID can become a majority of his or her day.