Extended-Release Amantadine Offers More Predictable Good ON Time for Those With Parkinson Disease

Robert A. Hauser, MD, MBA

According to pooled phase 3 data presented at the 2nd Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 8 to 11, 2023, in Washington, DC, the use of extended-related amantadine (Gocovri; Supernus) for patients with Parkinson disease (PD) might offer clinicians an ability to increase the predictability of good ON time from day to day.

“Such observations may have important implications on the ability to participate in daily activities for [people with PD], and as such, the relationship between predictability and good quality of life merits further investigation,” first author Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorders Center at the University of South Florida, and colleagues, wrote.

All told, the least-squares mean change from baseline in predictable good ON hours per day in paired intervals was significant at all time points for those on extended-release amantadine (n = 100) compared with those on placebo (n = 96). For those on amantadine, these changes were 4.3 hours at week 2 (mixed models for repeated measures treatment effect, 2.8; P <.0001), 5.05 hours at week 8 (treatment effect, 2.9; P <.0001), and 4.9 hours at week 12 (treatment effect, 2.95; P <.0001); comparatively, those on placebo recorded changes of 1.5 hours, 2.1 hours, and 1.95 hours, respectively. In an analysis of covariance for weeks 8 and 12 combined, the change for the treatment group was 2.6 hours compared with –0.85 hours for those on placebo (treatment effect, 3.4; P <.0001).

Good ON time over the course of the waking day was calculated by tallying the percentage of matched diary intervals that were concordant for good ON and dividing this percentage by the number of matched intervals where neither interval was recorded when the patient was sleeping. Participants recorded their predominant motor state in their home diaries in 30-minute intervals over the course of 2 consecutive days.

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At baseline, patients in the amantadine group reported a mean OFF time of 3.0 hours (SD, 2.3) and those in the placebo group reported 2.6 hours (SD, 2.0). The percentage of concordance for good ON time was 31.0% (SD, 18.5) for the amantadine group and 31.5% (SD, 18.1) for the placebo group. Notably, this rate included only 98 of 100 patients in the treatment arm.

“When calculated in hours instead of percentages, participants had just over 5 hours per day of ‘predictable’ good ON time at baseline. This nearly doubled to just over 10 hours per day at Week 12 for those receiving amantadine extended-release vs just over 7 hours per day for placebo,” Hauser et al wrote. This ultimately equated to a treatment difference of 2.95 hours per day (P <.0001), with awake time remaining relatively steady over the course of the study. By week 12, both groups saw patients awake for about 17 hours (based on the paired “awake” diary intervals).

This separation in predictable good ON time began as early as week 2, with the treatment arm reporting 9.6 hours compared with 6.7 hours for the placebo group. This was maintained through week 8 (amantadine, 10.3; placebo, 7.3) and week 12 (amantadine, 10.3; placebo, 7.1), and in the combined week 8 and 12 analysis (amantadine, 8.0; placebo, 4.4). In percentages, those values at week 2, week 8, and week 12 for the amantadine group were 55%, 60%, and 61% compared with 40%, 44%, and 43% for the placebo group (P <.0001 for all). In the combined weeks 8 and 12 analysis, the percentages were 45% for the amantadine group and 25% for the placebo group.

“The emergence of unpredictable levodopa-related motor complications adds extra burden to people with Parkinson disease, making it particularly difficult to plan daily activities,” Hauser et al wrote. “We have previously reported that, compared with placebo, patients treated with [extended-release amantadine] experienced fewer, shorter episodes of both troublesome dyskinesia and OFF, thereby increasing the duration of continuous good ON episodes (meaning ON without troublesome dyskinesia) and reducing the frequency of transitions between motor states.”

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REFERENCE
Hauser RA, Formella AE, Qin OP, Grall MS. Predictability of GOOD ON Time During the Waking Day with Amantadine Extended-Release Capsules A Post-hoc Analysis of Pooled Pivotal Trials. Presented at: ATMRD; June 9-11, 2023; Washington, DC.