Abbott announced the results from a Phase 3 trial evaluating the company's investigational compound for advanced Parkinson's disease, levodopa-carbidopa intestinal gel (LCIG).
The study showed that patients treated with LCIG for 12 weeks reported clinically meaningful and statistically significant improvements in "off" time compared to levodopa-carbidopa immediate release (IR) tablets, without increasing troublesome dyskinesia.
“Off” time refers to the periods of poor mobility, slowness and stiffness experienced by patients with Parkinson's disease. The results from the study will be presented as part of the Emerging Science program (formerly known as Late-Breaking) at the American Academy of Neurology's 64th Annual Meeting in New Orleans on April 25.
This study was conducted to determine the efficacy, safety and tolerability of continuous LCIG infusion in patients with advanced Parkinson's disease compared to standard levodopa-carbidopa IR tablets.
LCIG contains the same active medication as levodopa-carbidopa IR tablets but in gel form and is administered directly into the small intestine via a procedurally-implanted tube connected to a portable pump. At baseline, patients enrolled in the study had Parkinson's disease for an average of 10.9 years and experienced an average of 6.6 hours of "off" time a day.
The primary efficacy endpoint was change from baseline in daily "off" time (16 waking hours) at 12 weeks.
Mean "off" time at 12 weeks decreased by 4.0 hours per day with LCIG, an average of 1.91 fewer hours of "off" time compared to levodopa-carbidopa IR tablets.
The secondary efficacy endpoint was change from baseline in daily "on" time without troublesome dyskinesias. "On" time refers to periods of good motor symptom control.
Mean “on” time improved by 4.1 hours with LCIG, an average of 1.86 more hours compared to levodopa-carbidopa IR tablets.
Treatment-emergent adverse events (AE) occurred in 35 patients on LCIG (95 percent) and in 34 patients on levodopa-carbidopa IR tablets (100 percent) and were similar between the two treatment groups.
The most common adverse events were complication of device insertion (51 percent), abdominal pain (42 percent), procedural pain (32 percent), nausea (25 percent), constipation (21 percent), orthostatic hypotension (18 percent), post-operative wound infection (17 percent), and incision site erythema (16 percent).
Treatment-related serious adverse events (SAE) were reported in five patients (14 percent) in the LCIG arm and in seven patients (21 percent) in the levodopa-carbidopa IR tablets arm. All patients that experienced an SAE recovered. Premature discontinuation because of AEs was low (4.2 percent), and similar between treatment groups.
"These results demonstrate that continuous delivery of levodopa-carbidopa intestinal gel produces statistically meaningful improvements in advanced PD patients by decreasing 'off' time and increasing 'on' time without troublesome dyskinetic symptoms," said Dr. C.W. Olanow, M.D., Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York City. "These benefits in a patient group that cannot be satisfactorily controlled with standard levodopa, represent an important step forward in our efforts to treat advanced PD patients."
Parkinson's disease is a movement disorder resulting from progressive loss of brain cells that produce the chemical dopamine. Dopamine helps control movement of the body. Early on in the disease, patients usually respond well to medications that increase dopamine levels. As the disease progresses, the effect of oral medications may not last as long and can cause increasing side effects.
Patients with advanced Parkinson's disease may experience fluctuations between periods of poor mobility or slowness and periods when disease symptoms are well controlled. The loss in mobility or slowness/stiffness and periods of good symptom control are referred to as "off" time and "on" time, respectively.
When "off" time increases, a patient's "on" time progressively shortens. Additionally, many patients experience dyskinesias, which are involuntary movements associated with treatments used to manage Parkinson’s disease. Some of these involuntary movements can bother patients and make it difficult to perform activities. These are referred to as "troublesome dyskinesias."
"Parkinson's disease is a devastating condition that gets increasingly more difficult to treat as it progresses. In the later stages, patients have a disease burden that negatively impacts their quality of life and can impact normal activities of daily living," said Robert Lenz, M.D., divisional vice president, Global Pharmaceutical Research and Development, Abbott. "Many patients at this stage are in need of additional treatment options, and we hope that LCIG may soon be a viable option for some of these patients."
LCIG is an investigational therapy that is currently being evaluated in patients with advanced-stage Parkinson’s disease in additional Phase 3 clinical trials in the U.S. It is approved in 40 countries outside the U.S.
About the Study
LCIG was studied in a recently completed 12-week, double-blind, double-dummy (meaning all patients were given both placebo and active doses of either oral medication or LCIG during the study), multi-site efficacy and safety trial in patients with advanced Parkinson's disease and severe motor fluctuations despite optimized treatment with oral medications. In order to enroll, subjects had to be responsive to oral levodopa and experience a minimum of three hours of daily "off" time.
LCIG was administered via a procedurally-implanted tube connected to a portable pump that delivers the medication directly into the small intestine, where it is absorbed into the bloodstream, providing a continuous delivery of medication during the 16 hours a day of pump use.
Primary efficacy outcomes were measured using the Parkinson's Disease Diary-derived parameters. Secondary outcomes were assessed using tools including the Parkinson's Disease Questionnaire (PDQ-39), Clinical Global Impression-Improvement (CGI-I) and Unified Parkinson's Disease Rating Scale (UPDRS) scores, parts two and three.
About Parkinson's Disease
In the United States, it is estimated that 50,000 to 60,000 new cases of Parkinson's disease are reported each year, adding to the 864,000 people who currently have the disease. Approximately 20 percent of people living with Parkinson’s disease in the United States are considered advanced patients.
Parkinson's disease is a progressive and chronic movement 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 60-80 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.