Safety and Efficacy of Five Years of Levodopa–Carbidopa Intestinal Gel Treatment

PORTLAND, OR—Most patients with advanced Parkinson’s disease who received levodopa–carbidopa intestinal gel in an open-label, continued-access-to-treatment study had, at five years, transitioned to using the therapy outside of the study when it became commercially available or continued to participate in the extension study, according to data presented at the Fourth World Parkinson Congress.

Forty-two percent of the patients in the phase III extension study transitioned to commercially available drug (designated as carbidopa–levodopa enteral suspension in the United States), and 24% of patients remained in the multinational study, said Hubert H. Fernandez, MD, Head of Movement Disorders at the Center for Neurological Restoration at the Cleveland Clinic in Ohio, and colleagues. Patients may remain in the extension study until a commercially available product is available in the country where they live.

Levodopa–carbidopa intestinal gel is infused continuously directly to the jejunum using a portable pump during approximately 16 hours of wakefulness. The therapy is designed to overcome some of the limitations of oral levodopa, which may lose effectiveness as Parkinson’s disease progresses.

Although investigators observed a high incidence of adverse events, long-term use of levodopa–carbidopa intestinal gel was well tolerated, the researchers said. The average discontinuation rate of 9.6% per year, including all causes of death, was relatively low, Dr. Fernandez and colleagues said.

The most frequently reported adverse events were associated with complications related to percutaneous gastrojejunostomy, such as stoma site maintenance. Other adverse events were associated with advanced Parkinson’s disease, aging, or levodopa. Most patients experienced device malfunctions and required pump replacement during the study.

The extension study began in November 2009. Data through September 30, 2015, were used in the present study. The study enrolled 262 patients with advanced Parkinson’s disease from 11 countries who had completed a 12-week double-blind study and its 52-week open-label extension or who had completed a separate 54-week open-label study. Participants attended scheduled study visits every six months.

Patients had a mean age of 64, 62% were male, and mean disease duration was 11.4 years. Mean exposure to levodopa–carbidopa intestinal gel was 3.1 years in the present study. Patients’ mean total exposure to the treatment was 4.1 years. Fifty-six percent of patients were exposed to the treatment for at least five years.

Adverse events led to discontinuation in 62 patients (24%). Device complaints occurred in 244 patients (93%). The most common device complaints included device malfunction (85%), device occlusion (57%), and device dislocation (56%). Thirty-eight patients died during the study. Two patients died as a result of intestinal dilatation and cardiac arrest, which an investigator considered possibly related to the treatment.

As part of an amended study protocol, patients in the United States began completing efficacy assessments in December 2013 (ie, Parkinson’s disease diary, Unified Parkinson’s Disease Rating Scale, and the Parkinson’s Disease Questionnaire). Patients in the United States showed sustained and clinically meaningful benefits of treatment that were demonstrated by decreased off time and increased on time without troublesome dyskinesia, the researchers concluded.

—Jake Remaly

PORTLAND, OR—Most patients with advanced Parkinson’s disease who received levodopa–carbidopa intestinal gel in an open-label, continued-access-to-treatment study had, at five years, transitioned to using the therapy outside of the study when it became commercially available or continued to participate in the extension study, according to data presented at the Fourth World Parkinson Congress.

Forty-two percent of the patients in the phase III extension study transitioned to commercially available drug (designated as carbidopa–levodopa enteral suspension in the United States), and 24% of patients remained in the multinational study, said Hubert H. Fernandez, MD, Head of Movement Disorders at the Center for Neurological Restoration at the Cleveland Clinic in Ohio, and colleagues. Patients may remain in the extension study until a commercially available product is available in the country where they live.

Levodopa–carbidopa intestinal gel is infused continuously directly to the jejunum using a portable pump during approximately 16 hours of wakefulness. The therapy is designed to overcome some of the limitations of oral levodopa, which may lose effectiveness as Parkinson’s disease progresses.

Although investigators observed a high incidence of adverse events, long-term use of levodopa–carbidopa intestinal gel was well tolerated, the researchers said. The average discontinuation rate of 9.6% per year, including all causes of death, was relatively low, Dr. Fernandez and colleagues said.

The most frequently reported adverse events were associated with complications related to percutaneous gastrojejunostomy, such as stoma site maintenance. Other adverse events were associated with advanced Parkinson’s disease, aging, or levodopa. Most patients experienced device malfunctions and required pump replacement during the study.

The extension study began in November 2009. Data through September 30, 2015, were used in the present study. The study enrolled 262 patients with advanced Parkinson’s disease from 11 countries who had completed a 12-week double-blind study and its 52-week open-label extension or who had completed a separate 54-week open-label study. Participants attended scheduled study visits every six months.

Patients had a mean age of 64, 62% were male, and mean disease duration was 11.4 years. Mean exposure to levodopa–carbidopa intestinal gel was 3.1 years in the present study. Patients’ mean total exposure to the treatment was 4.1 years. Fifty-six percent of patients were exposed to the treatment for at least five years.

Adverse events led to discontinuation in 62 patients (24%). Device complaints occurred in 244 patients (93%). The most common device complaints included device malfunction (85%), device occlusion (57%), and device dislocation (56%). Thirty-eight patients died during the study. Two patients died as a result of intestinal dilatation and cardiac arrest, which an investigator considered possibly related to the treatment.

As part of an amended study protocol, patients in the United States began completing efficacy assessments in December 2013 (ie, Parkinson’s disease diary, Unified Parkinson’s Disease Rating Scale, and the Parkinson’s Disease Questionnaire). Patients in the United States showed sustained and clinically meaningful benefits of treatment that were demonstrated by decreased off time and increased on time without troublesome dyskinesia, the researchers concluded.

—Jake Remaly

PORTLAND, OR—Most patients with advanced Parkinson’s disease who received levodopa–carbidopa intestinal gel in an open-label, continued-access-to-treatment study had, at five years, transitioned to using the therapy outside of the study when it became commercially available or continued to participate in the extension study, according to data presented at the Fourth World Parkinson Congress.

Forty-two percent of the patients in the phase III extension study transitioned to commercially available drug (designated as carbidopa–levodopa enteral suspension in the United States), and 24% of patients remained in the multinational study, said Hubert H. Fernandez, MD, Head of Movement Disorders at the Center for Neurological Restoration at the Cleveland Clinic in Ohio, and colleagues. Patients may remain in the extension study until a commercially available product is available in the country where they live.

Levodopa–carbidopa intestinal gel is infused continuously directly to the jejunum using a portable pump during approximately 16 hours of wakefulness. The therapy is designed to overcome some of the limitations of oral levodopa, which may lose effectiveness as Parkinson’s disease progresses.

Although investigators observed a high incidence of adverse events, long-term use of levodopa–carbidopa intestinal gel was well tolerated, the researchers said. The average discontinuation rate of 9.6% per year, including all causes of death, was relatively low, Dr. Fernandez and colleagues said.

The most frequently reported adverse events were associated with complications related to percutaneous gastrojejunostomy, such as stoma site maintenance. Other adverse events were associated with advanced Parkinson’s disease, aging, or levodopa. Most patients experienced device malfunctions and required pump replacement during the study.

The extension study began in November 2009. Data through September 30, 2015, were used in the present study. The study enrolled 262 patients with advanced Parkinson’s disease from 11 countries who had completed a 12-week double-blind study and its 52-week open-label extension or who had completed a separate 54-week open-label study. Participants attended scheduled study visits every six months.

Patients had a mean age of 64, 62% were male, and mean disease duration was 11.4 years. Mean exposure to levodopa–carbidopa intestinal gel was 3.1 years in the present study. Patients’ mean total exposure to the treatment was 4.1 years. Fifty-six percent of patients were exposed to the treatment for at least five years.

Adverse events led to discontinuation in 62 patients (24%). Device complaints occurred in 244 patients (93%). The most common device complaints included device malfunction (85%), device occlusion (57%), and device dislocation (56%). Thirty-eight patients died during the study. Two patients died as a result of intestinal dilatation and cardiac arrest, which an investigator considered possibly related to the treatment.

As part of an amended study protocol, patients in the United States began completing efficacy assessments in December 2013 (ie, Parkinson’s disease diary, Unified Parkinson’s Disease Rating Scale, and the Parkinson’s Disease Questionnaire). Patients in the United States showed sustained and clinically meaningful benefits of treatment that were demonstrated by decreased off time and increased on time without troublesome dyskinesia, the researchers concluded.

—Jake Remaly