Long-term treatment with Gocovri (amantadine) extended-release capsules was safe and led to sustained reductions in dyskinesia — involuntary, jerky movements — and off episodes in people with Parkinson’s disease, final data from a two-year Phase 3 clinical trial show.
“As the longest-running amantadine study to date, this open-label trial suggests Gocovri may provide sustained improvement in both dyskinesia and OFF [episodes] to a wide cohort of patients with Parkinson’s disease living with motor complications,” Caroline Tanner, MD, professor in the department of neurology at the University of California San Francisco, said in a press release.
“These results expand not only our knowledge of Gocovri efficacy but also of its long-term safety in these patients,” Turner said.
The study, “EASE LID 2: A 2-Year Open-Label Trial of Gocovri (Amantadine) Extended Release for Dyskinesia in Parkinson’s Disease,” was published in the Journal of Parkinson’s Disease.
While levodopa is one of the gold standard treatment to manage Parkinson’s motor symptoms, long-term use may lead to off-episodes, which are moments in which the therapy’s effects wear off and symptoms, including dyskinesia, re-emerge.
Adamas Pharmaceuticals’ Gocovri, a long-acting and extended-release oral capsule amantadine formulation, is the only U.S.-approved treatment for dyskinesia in Parkinson’s patients who receive levodopa-based therapy, with or without other dopaminergic medications. It also is the only therapy clinically proven to lessen both Parkinson’s dyskinesia and off episodes.
Taken once daily at bedtime, Gocovri levels rise slowly overnight and achieve their peak in the morning (before the patient’s first levodopa dose), maintaining its high levels throughout the waking day.
The two-year, open-label Phase 3 EASE LID 2 clinical trial (NCT02202551) evaluated the long-term safety, tolerability, and effectiveness of Gocovri in Parkinson’s patients with levodopa-induced dyskinesia for two years.
The study was designed to reflect conditions closer to a “real-world” clinical setting by including not only patients who completed previous Gocovri trials — EASED (NCT01397422), EASE LID (NCT02136914) and EASE LID 3 (NCT02274766 ) — but also those excluded from these trials because they had deep brain stimulation (DBS) therapy. It also allowed clinicians to adjust doses of levodopa and other Parkinson’s medications.
DBS is the most common surgery used to treat Parkinson’s symptoms by delivering electrical pulses to brain cells.
A total of 223 patients were recruited, including 138 who transitioned directly from previous clinical trials (60 receiving Gocovri and 78 a placebo), 61 with prior DBS surgery, and 24 who had a time gap between the prior trial and the EASE LID 2 study.
Among them, 32 patients (24 who underwent DBS and eight among those with a time gap between trials) were switched directly from amantadine immediate-release to Gocovri when entering EASE LID 2.
Most patients were white (93.3%) and more than half (58.7%) were men. Participants’ mean (average) age was 63.7 years at enrollment and they had been diagnosed with Parkinson’s for a mean of 11.8 years. Patients had been taking levodopa for a mean of 9.3 years, with reports of dyskinesia for about 5.3 years.
During the trial, participants received Gocovri once daily at bedtime for a median of 1.9 years, with 75.8% of them having completed one year of treatment and 57.8% completing two years of treatment.
The therapy’s effectiveness was assessed using the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part IV (focused on motor complications). Higher scores indicate greater impact of Parkinson’s symptoms, and changes of at least one point in the MDS-UPDRS Part IV score are considered clinically important.
Results showed that Gocovri was effective in lowering dyskinesia and off episodes in all groups of patients, including those who continued treatment from prior trials and those initiating Gocovri in this trial (patients switching from placebo or amantadine immediate release, and those under DBS therapy).
Low levels of motor complications were maintained in patients continuing Gocovri treatment from prior trials. Those initiating Gocovri in this trial showed marked reductions (between two and four points) in the MDS-UPDRS Part IV score, reaching the same levels as those with continuous treatment after eight weeks (the first scheduled effectiveness assessment). These improvements were maintained throughout the two-year trial.
“The present long-term trial provides supportive evidence that 274 mg Gocovri, taken once daily at bedtime, durably reduces the daily duration, severity, and functional impact of dyskinesia as well as OFF episodes throughout 100 weeks of continued use,” the researchers wrote.
Gocovri’s safety profile and rate of treatment discontinuations (22%) were consistent with those reported in previous clinical trials. Common adverse side effects included falls (32.7%), hallucinations (24.2%), swelling in the legs or arms (16.1%), constipation (13.5%), and urinary tract infections (10.3%).
Not surprisingly, adverse side effects’ onset and related treatment discontinuations tended to occur earlier among those just beginning Gocovri treatment than among those continuing treatment from a prior trial.
Jean Hubble, MD, Adamas’ vice president of medical affairs, said that “given the chronic nature of Parkinson’s disease, both patients and physicians seek treatments that are effective long-term.”
“This study further demonstrates that the only FDA-approved medicine for dyskinesia may help people with PD who are struggling to manage these levodopa-related motor complications over this long period of time,” Hubble said.