Abbott Reports Interim Results from Phase III Open-Label Study of Investigational Treatment for Advanced Parkinson's Disease
In a 54-week study, after 12 weeks of treatment with levodopa-carbidopa intestinal gel, patients reported improvement in motor symptoms
Abbott Park, Illinois (NYSE: ABT) - Interim efficacy and safety results from a long-term, 54-week, Phase III open-label study of Abbott's investigational treatment for advanced Parkinson's disease showed that patients treated with levodopa-carbidopa intestinal gel (LCIG) for 12 weeks reported a decrease in "off" time and an increase in "on" time without troublesome dyskinesias. The results were reported at the International Congress of Parkinson's Disease and Movement Disorders in Toronto.
Parkinson's disease is a movement disorder resulting from progressive neurodegeneration of certain brain regions. As their disease progresses, most patients with Parkinson's disease treated with oral medications experience re-emergence of some of their symptoms, resulting in a loss of mobility. This is known as "off" time. When "off" time increases, a patient's "on" time - when disease symptoms are well managed - progressively shortens. Additionally, most patients also may experience dyskinesias, involuntary movements associated with most treatments used to manage the disease. LCIG is infused directly and continuously during daytime hours into the small intestine via a portable pump connected to a surgically-implanted gastric tube. Continuous delivery may help reduce spikes in drug levels in the blood due to the inconsistent absorption that happens with oral medications. These spikes are associated with increases in dyskinesias.
In an interim analysis of the long-term study, data were analyzed from 192 patients with advanced Parkinson's disease who had completed 12 weeks of treatment with LCIG for 16 hours per day. The primary efficacy endpoint is change from baseline to endpoint in "off" time at 54 weeks. At 12 weeks, patients reported an average of 3.9 fewer hours of "off" time and 4.6 additional hours of "on" time without troublesome dyskinesias. Adverse events occurred in 168 patients (87.5 percent) and appeared to be largely related to the surgical procedure.
The most common adverse events were abdominal pain (30.7 percent), complications of device insertion (21.4 percent) and procedural pain (17.7 percent). The most severe complications from surgery were peritonitis (abdominal inflammation, 3.6 percent) and pneumoperitoneum (gas or air in the peritoneal cavity, 5.7 percent). Fourteen patients (7.3 percent) withdrew due to an adverse event.
"With advanced Parkinson's disease, the goal of treatment is to provide patients with as much "on" time as possible, while limiting the troublesome dyskinesias they may experience," said Alberto Espay, M.D., assistant professor of neurology, University of Cincinnati Neuroscience Institute, director of clinical research, Gardner Family Center for Parkinson's disease and one of the lead investigators. "The interim data from this study of LCIG show clinically meaningful improvements in these important measures."
LCIG is an investigational therapy that is being evaluated for the treatment of advanced-stage Parkinson's disease to achieve continuous dopaminergic stimulation for up to 16 hours. Oral forms of levodopa and carbidopa have been used in the treatment of Parkinson's disease for more than 40 years. As the disease progresses, patients may experience motor fluctuations that increase in severity and become difficult to treat. LCIG is administered via a surgically-implanted tube connected to a portable pump that delivers the medication directly to the small intestine, where it is then absorbed into the bloodstream, providing a continuous delivery of medication.
"Patients with advanced Parkinson's disease currently have few treatment options to help them manage the disease and it becomes progressively more debilitating," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott. "We look forward to additional data from ongoing studies and will continue our efforts to bring LCIG forward as a potential option for patients who no longer respond adequately to optimized oral treatment."
LCIG currently is in Phase III development in the United States and is approved for use in 38 countries.
About the Study
LCIG is being studied in an ongoing 54-week, open-label, multi-site efficacy and safety trial in patients with advanced Parkinson's disease and severe motor fluctuations despite optimized treatment with available medications.
To be included in the study, all patients had to be levodopa-carbidopa responders, as determined by a two-to-14-day test period during which a tube inserted through the nose delivered the medications directly to the jejunum, part of the small intestine. If successful, patients underwent a surgical procedure to implant an intrajejunal percutaneous endoscopic gastrostomy (PEG-J) tube in the abdomen. The tube connects to a pump worn and controlled by the patient. Individualized dosing of LCIG is administered for 16 hours per day and other Parkinson's disease medications are permitted after 28 days.
Efficacy outcomes include patient-diary-assessed "off" time, "on" time with troublesome dyskinesias, "on" time without troublesome dyskinesias and Unified Parkinson's Disease Rating Scale (UPDRS) scores.
Additional adverse events occurring in more than 10 percent of patients included constipation (13.5 percent), nausea (13.5 percent), excessive granulation tissue (13.5 percent), fall (10.9 percent), dyskinesia (10.9 percent), insomnia (10.9 percent), post-operative wound infection (10.4 percent) and anxiety (10.4 percent).
About Parkinson's Disease
In the United States, it is estimated that 50,000 to 60,000 new case of Parkinson's disease are reported each year, adding to the 1 million people who currently have the disease.
Parkinson's disease is a chronic, progressive brain disorder that leads to tremor, muscle rigidity, slowness of movement and difficulty with balance. It is classified as a movement disorder, which results from the loss of dopamine-producing brain cells. The symptoms of Parkinson's disease begin when approximately 80 percent of the dopamine-producing cells in the brain are lost and symptoms continue to worsen slowly over the course of time. While there is no known cure for the disease, there are treatments available to help reduce symptoms.
In the early stages of Parkinson's disease, symptoms can be reduced with oral medication. However, as the disease progresses, patients may develop severe fluctuations in motor control.
Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs nearly 90,000 people and markets its products in more than 130 countries.