Phase 3 Trial Protocol Amended for Parkinson’s Therapy Accordion Pill Carbidopa/Levodopa
Intec Pharma recently announced that the protocol for the global Phase 3 Accordance clinical trial (NCT02605434) has been amended. The Accordance trial, which is currently recruiting patients, is evaluating the Accordion Pill Carbidopa/Levodopa to treat symptoms of Parkinson’s disease in patients with advanced stage disease.
Following suggestions from key opinion leaders and biostatisticians with expertise in Parkinson’s, the trial amendment, already reviewed and accepted by the U.S. Food and Drug Administration (FDA), reduces the study’s sample size from 460 to 328 patients, but maintains the study goals, endpoints, and statistical power (90%).
Accordance is a Phase 3 randomized clinical trial currently evaluating the effectiveness of the Accordion Pill in combination with two primary drugs for Parkinson’s treatment, carbidopa and levodopa (known as Accordion Pill Carbidopa/Levodopa) in reducing the percentage of daily “off time” motor fluctuations during waking hours in people with advanced Parkinson’s (the studys’ primary effectiveness endpoint).
The trial is comparing the Accordion Pill with Sinemet (immediate release carbidopa-levodopa, which is already FDA-approved). The study is being conducted in the U.S., Europe, and Israel. Information on enrolling in the study can be found here.
Intec’s Accordion Pill is a technology platform that allows for the prolonged absorption of drugs with a small absorption window, such as the combination of carbidopa and levodopa for the treatment of Parkinson’s disease. According to Intec, between 30 percent and 45 percent of medications currently on the market are poorly soluble, a problem the Accordion Pill addresses by retaining the dosage form in the stomach and then gradually releasing the medication into the upper part of the gastrointestinal tract.
“The amended protocol’s sample size estimation uses a predicted standard deviation that is based on recent evidence from similar Parkinson’s disease clinical trials,” Karl Kieburtz, MD, president of Clintrex and a consultant to Intec, said in a press release.
“Using this estimated standard deviation and the same predicted difference between the active intervention and control, we achieve a substantial savings in sample size without altering the objectives, endpoints or statistical power of the Accordance Study,” said Kieburtz, also a professor in the Department of Neurology at the University of Rochester.
Intec CEO Zeev Weiss said levodopa is the “most effective and widely used treatment for Parkinson’s disease symptoms. However, reports indicate that up to 50 percent of patients show onset of motor fluctuations within two years of starting conventional levodopa therapy.”
“We believe that our AP-CD/LD, currently being tested in Phase 3, holds huge potential in addressing a major unmet need for many Parkinson’s disease patients — to improve duration and consistency of symptom relief provided by levodopa,” he said.
“We are excited to continue to advance our Phase 3 Accordance Study with this protocol amendment as it enables a significant reduction in sample size without altering the study’s original objectives, endpoints and statistical power of 90 percent or eventual outcomes,” Weiss added. “We believe that the reduction in sample size should shorten study completion timelines and reduce overall costs, and we expect to complete patient enrollment in the fourth quarter of 2017.”
Patients with advanced Parkinson’s usually develop motor fluctuations, the result of variations in the individual’s response to levodopa. Motor fluctuations oscillate between “off” times, a state of decreased mobility, and “on” times, or periods when the medication is working and symptoms are controlled.
“We are committed to providing a replacement levodopa treatment to advanced Parkinson’s disease patients that experience ‘Off times’ for hours during a typical waking day,” Weiss said. “Our goal is to improve the current treatment of this very prevalent and severe neurodegenerative disease.”