Clinical Trial Highlights: Phase 3 Trials in Focus

Phase 3 studies need particular attention as they are the closest to market, so each edition of Clinical Trial Highlights will have a 'Phase 3 in Focus', selecting one study for analysis. These are listed on the overview of articles on the main Clinical Trial Highlights page here, and below is a list of short extracts from each article. Click the "Read More" link to access the full analysis in the JPD article on the IOS Press Content Library.


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Amneal's IPX203

(Publication Date: January 2020)

Background: There is a clear clinical need for oral formulations of levodopa that deliver optimal levels in the bloodstream for extended periods of time. Whilst such formulations exist and are used, for example, Sinemet CR and Rytary, there is still considerable room for improvement. Impax Laboratories, acquired by Amneal in 2018, sells Rytary, but are also developing IPX203, aimed to have a longer half-life than Rytary. Both drugs are manufactured as capsules containing different particle forms of levodopa and carbidopa (LD/CD). The mix of particles enables the combination of immediate release (IR) of LD/CD together with sustained release LD/CD over an extended period of time. READ MORE


Adamas Pharma's Gocovri

(Publication Date: July 2019)

Background: The Phase 3 in focus for this edition of Clinical Trial Highlights continues the theme of symptomatic relief of dyskinesia in PD. We will review two Phase 3 trials already completed on amantadine ER (Gocovri), previously known as ADS-5102 during development, EASE LID and EASE LID 3. Gocovri is a capsule containing 137mg extended-release amantadine, an uncompetitive antagonist at the N-methyl-D-aspartate receptor known to have benefit to relieve the symptoms of dyskinesia and currently the only available molecule for management of dyskinesia. The rationale of extended release is to provide a therapeutic level of amantadine in the blood for a longer period of time, in this case enabling once a day dosing. Two capsules are administered at bedtime to give a slow increase during sleep, peak levels in the morning and a sustained concentration during the day. READ MORE


Intec Pharma's Accordian Pill

(Publication Date: May 2019)

Background: Levodopa remains the most potent symptomatic therapy for PD. One of the major limitations of levodopa therapy is the risk of development of motor fluctuations and dyskinesia related to the short half life of the drug, coupled with progressive decline of neuronal dopamine storage capacity. Current formulations of levodopa are generally taken every few hours, leading to a pulsatile profile of peaks and troughs. The peaks can induce troublesome dyskinesia while the troughs can lead to OFF time with significant symptom breakthrough. A steadier and more consistent plasma profile should reduce the incidence of both types of motor fluctuation as well as reducing the number of tablets patients need to take. Intec Pharma have developed the Accordion Pill, a gastric-retentive capsule containing multiple layers of both immediate release and controlled release levodopa and carbidopa. The pill remains in the stomach for up to 12 hours. READ MORE


Isradipine

(Publication Date: February 2019)

Background: Isradipine, a dihydropyridine calcium channel antagonist (DHP) that is approved for the treatment of hypertension, is being tested as a potential disease modifying intervention in early PD. Isradipine was shown to be neuroprotective in in vitro and in vivo models of parkinsonism. The mechanism of neuroprotection is linked to selective vulnerability of substantia nigra pars compacta neurons that preferentially express L-type calcium channels. Neuroprotective effects of isradipine are achieved at a plasma concentration that is obtained within the safe dose range for human administration and consistent with the tolerable dosage identified in the phase II study of isradipine in PD (STEADY-PDII). A number of epidemiological studies have demonstrated a reduced risk of development of PD in individuals treated with DHPs compared to other antihypertensive agents. READ MORE