Gocovri Leads to Steady ‘On’ States in Parkinson’s Patients, Phase 3 Pooled Data Suggest

Gocovri (amantadine) can effectively reduce the number and duration of “off” periods and dyskinesia (uncontrolled movement) episodes in Parkinson’s patients under long-term levodopa treatment, leading to a good steady “on” state, pooled Phase 3 clinical data show.

These findings were reported in a study, “Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials,” that was published in the Journal of Parkinson’s Disease.

Levodopa is a precursor of dopamine and one of the gold-standard treatments to manage the motor symptoms of Parkinson’s disease. However, patients who take it over extended periods develop off-episodes, moments in which the therapy losses its effect and involuntary movements (dyskinesia) reappear.

Some adjustments and alternative treatments, such as Gocovri (marketed by Adamas Pharmaceuticals), can help control these off-episodes and dyskinesia. But it is not clear how these treatments act as a whole.

Therefore, the researchers reviewed the effects of Gocovri from data collected during two Phase 3 placebo-controlled trials, called EASE LID (NCT02136914) and EASE LID 3 (NCT02274766).

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The analysis included data from 162 Parkinson’s patients who participated in these trials, of whom 77 received Gocovri and 85 received a placebo for 12 weeks. The patients had a mean age of 64.5 years, had been diagnosed with Parkinson’s disease for 9.9 years, and had been taking levodopa for about 7.6 years.

During the trials, patients kept diaries in which they were asked to detail their daily on- and off-periods, and events of dyskinesia. Patients divided their awake time into 30-minute intervals and reported the state they were in at each interval.

Three main states were considered: “on” without troublesome dyskinesia (good “on”), “on” with troublesome dyskinesia (troublesome dyskinesia), and off-periods. Troublesome dyskinesia referred to involuntary movements that impaired, at least partially, the performance of daily functions.

Most patients (67%) reported waking up in an off-state, which decreased to 13% of patients during the first two awake hours. Thereafter, the number of patients in each state remained constant throughout the day.

A lower number of patients (5%) woke up experiencing troublesome dyskinesia, which in contrast increased up to 24% within the two hours after being awake, then fluctuated between 20% and 44% through the rest of the waking day.

Patients were found to experience a mean of 3.0 episodes of troublesome dyskinesia and about 2.2 off-episodes during the day. The mean duration of each episode was approximately two hours for dyskinesia and 1.1 hours for an off-episode.

After taking Gocovri for 12 weeks, the proportion of patients reporting no episodes of “on” with troublesome dyskinesia was 57.1%, compared with 24.7% in the placebo group. The treatment also reduced the mean duration of the episodes and the mean number of transitions between states during the day, leading to a steadier good “on” state during the day.

In general, the treatment was found to be safe, with less than 10% of patients experiencing adverse events. The most common adverse events were dizziness, constipation, hallucinations, dry mouth, edema, swelling of the extremities, and urinary infections.

“Our results demonstrated a treatment effect of Gocovri for dyskinesia and OFF [states] throughout the waking day,” the researchers wrote.

“In the future, wearable sensors and other types of monitors may provide continuous monitoring through the day and allow more sensitive assessment of mild motor fluctuations and dyskinesia,” they said.

Of note, most of the researchers received compensation from or are employees of Adamas Pharmaceuticals.