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PORTLAND, OR—Amantadine hydrochloride extended-release capsules, compared with placebo, result in a statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia in patients with Parkinson’s disease, according to phase III trial results presented at the Fourth World Parkinson Congress. The drug also reduces daily off time and is generally well tolerated, researchers said.
Amantadine hydrochloride extended-release capsules, known as ADS-5102, are being developed by Adamas Pharmaceuticals with the aim of improving the pharmacokinetic profile of immediate-release amantadine.
Rajesh Pahwa, MD, Professor of Neurology at University of Kansas Medical Center in Kansas City, and colleagues reported efficacy and safety results from the EASE LID 3 trial, one of three phase III trials of the drug. 
EASE LID 3 was a randomized, double-blind, placebo-controlled study conducted at 39 sites in the United States and Europe. Seventy-seven patients with Parkinson’s disease were randomized to receive 340 mg of amantadine hydrochloride or placebo once daily at bedtime for the treatment of levodopa-induced dyskinesia. Participants had an average age of 64.8, 52% were men, and they had been diagnosed with Parkinson’s disease for an average of 10.6 years. They had received levodopa treatment for an average of 8.1 years. Patients’ mean duration of levodopa-induced dyskinesia was 3.9 years.
Treatment Improved Outcomes
The primary efficacy analysis compared the least square mean change from baseline to week 12 in Unified Dyskinesia Rating Scale total score in the ADS-5102 group with that in the placebo group. Key secondary efficacy analyses compared the least square mean change from baseline to week 12 in on time without troublesome dyskinesia and off time, as recorded in participants’ home diaries.
Thirty-eight patients were randomized to receive ADS-5102 and 39 patients were randomized to receive placebo. In the ADS-5102 group, the observed mean Unified Dyskinesia Rating Scale total score from baseline to week 12 decreased by 46%, compared with a 16% reduction in the placebo group. At 12 weeks, daily on time without troublesome dyskinesia increased by 4.0 hours in the ADS-5102 group and by 2.1 hours in the placebo group. Daily off time decreased by 0.5 hours in the ADS-5102 group and increased by 0.6 hours in the placebo group.
Adverse Events
Four patients, all in the ADS-5102 group, experienced serious adverse events. In one patient, the serious adverse event was considered related to the study drug (ie, constipation and urinary retention). The patient completed study treatment and did not discontinue participation in the trial.
Seven patients in the ADS-5102 group (19%) versus three patients in the placebo group (8%) discontinued treatment due to adverse events. In the ADS-5102 group, the most frequent adverse events (ie, they occurred in more than two patients) were dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, constipation, fall, and hallucination.
“ADS-5102 resulted in statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia, confirming results from earlier controlled clinical trials,” the researchers concluded.
Investigators are conducting an open-label safety study of ADS-5102 that includes patients from the phase III trials as well as patients with levodopa-induced dyskinesia who have undergone deep brain stimulation. Adamas also is investigating ADS-5102 for use in patients with multiple sclerosis with walking impairment.
—Jake Remaly
PORTLAND, OR—Amantadine hydrochloride extended-release capsules, compared with placebo, result in a statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia in patients with Parkinson’s disease, according to phase III trial results presented at the Fourth World Parkinson Congress. The drug also reduces daily off time and is generally well tolerated, researchers said.
Amantadine hydrochloride extended-release capsules, known as ADS-5102, are being developed by Adamas Pharmaceuticals with the aim of improving the pharmacokinetic profile of immediate-release amantadine.
Rajesh Pahwa, MD, Professor of Neurology at University of Kansas Medical Center in Kansas City, and colleagues reported efficacy and safety results from the EASE LID 3 trial, one of three phase III trials of the drug.
EASE LID 3 was a randomized, double-blind, placebo-controlled study conducted at 39 sites in the United States and Europe. Seventy-seven patients with Parkinson’s disease were randomized to receive 340 mg of amantadine hydrochloride or placebo once daily at bedtime for the treatment of levodopa-induced dyskinesia. Participants had an average age of 64.8, 52% were men, and they had been diagnosed with Parkinson’s disease for an average of 10.6 years. They had received levodopa treatment for an average of 8.1 years. Patients’ mean duration of levodopa-induced dyskinesia was 3.9 years.
Treatment Improved Outcomes
The primary efficacy analysis compared the least square mean change from baseline to week 12 in Unified Dyskinesia Rating Scale total score in the ADS-5102 group with that in the placebo group. Key secondary efficacy analyses compared the least square mean change from baseline to week 12 in on time without troublesome dyskinesia and off time, as recorded in participants’ home diaries.
Thirty-eight patients were randomized to receive ADS-5102 and 39 patients were randomized to receive placebo. In the ADS-5102 group, the observed mean Unified Dyskinesia Rating Scale total score from baseline to week 12 decreased by 46%, compared with a 16% reduction in the placebo group. At 12 weeks, daily on time without troublesome dyskinesia increased by 4.0 hours in the ADS-5102 group and by 2.1 hours in the placebo group. Daily off time decreased by 0.5 hours in the ADS-5102 group and increased by 0.6 hours in the placebo group.
Adverse Events
Four patients, all in the ADS-5102 group, experienced serious adverse events. In one patient, the serious adverse event was considered related to the study drug (ie, constipation and urinary retention). The patient completed study treatment and did not discontinue participation in the trial.
Seven patients in the ADS-5102 group (19%) versus three patients in the placebo group (8%) discontinued treatment due to adverse events. In the ADS-5102 group, the most frequent adverse events (ie, they occurred in more than two patients) were dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, constipation, fall, and hallucination.
“ADS-5102 resulted in statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia, confirming results from earlier controlled clinical trials,” the researchers concluded.
Investigators are conducting an open-label safety study of ADS-5102 that includes patients from the phase III trials as well as patients with levodopa-induced dyskinesia who have undergone deep brain stimulation. Adamas also is investigating ADS-5102 for use in patients with multiple sclerosis with walking impairment.
—Jake Remaly
PORTLAND, OR—Amantadine hydrochloride extended-release capsules, compared with placebo, result in a statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia in patients with Parkinson’s disease, according to phase III trial results presented at the Fourth World Parkinson Congress. The drug also reduces daily off time and is generally well tolerated, researchers said.
Amantadine hydrochloride extended-release capsules, known as ADS-5102, are being developed by Adamas Pharmaceuticals with the aim of improving the pharmacokinetic profile of immediate-release amantadine.
Rajesh Pahwa, MD, Professor of Neurology at University of Kansas Medical Center in Kansas City, and colleagues reported efficacy and safety results from the EASE LID 3 trial, one of three phase III trials of the drug.
EASE LID 3 was a randomized, double-blind, placebo-controlled study conducted at 39 sites in the United States and Europe. Seventy-seven patients with Parkinson’s disease were randomized to receive 340 mg of amantadine hydrochloride or placebo once daily at bedtime for the treatment of levodopa-induced dyskinesia. Participants had an average age of 64.8, 52% were men, and they had been diagnosed with Parkinson’s disease for an average of 10.6 years. They had received levodopa treatment for an average of 8.1 years. Patients’ mean duration of levodopa-induced dyskinesia was 3.9 years.
Treatment Improved Outcomes
The primary efficacy analysis compared the least square mean change from baseline to week 12 in Unified Dyskinesia Rating Scale total score in the ADS-5102 group with that in the placebo group. Key secondary efficacy analyses compared the least square mean change from baseline to week 12 in on time without troublesome dyskinesia and off time, as recorded in participants’ home diaries.
Thirty-eight patients were randomized to receive ADS-5102 and 39 patients were randomized to receive placebo. In the ADS-5102 group, the observed mean Unified Dyskinesia Rating Scale total score from baseline to week 12 decreased by 46%, compared with a 16% reduction in the placebo group. At 12 weeks, daily on time without troublesome dyskinesia increased by 4.0 hours in the ADS-5102 group and by 2.1 hours in the placebo group. Daily off time decreased by 0.5 hours in the ADS-5102 group and increased by 0.6 hours in the placebo group.
Adverse Events
Four patients, all in the ADS-5102 group, experienced serious adverse events. In one patient, the serious adverse event was considered related to the study drug (ie, constipation and urinary retention). The patient completed study treatment and did not discontinue participation in the trial.
Seven patients in the ADS-5102 group (19%) versus three patients in the placebo group (8%) discontinued treatment due to adverse events. In the ADS-5102 group, the most frequent adverse events (ie, they occurred in more than two patients) were dry mouth, nausea, decreased appetite, insomnia, orthostatic hypotension, constipation, fall, and hallucination.
“ADS-5102 resulted in statistically significant and clinically meaningful improvement in levodopa-induced dyskinesia, confirming results from earlier controlled clinical trials,” the researchers concluded.
Investigators are conducting an open-label safety study of ADS-5102 that includes patients from the phase III trials as well as patients with levodopa-induced dyskinesia who have undergone deep brain stimulation. Adamas also is investigating ADS-5102 for use in patients with multiple sclerosis with walking impairment.
—Jake Remaly
