Patients with persistent tremor sought for suvecaltamide trial
Treatment works by selectively blocking T-type calcium channels
Parkinson’s disease patients with inadequately controlled tremors are being sought for a Phase 2 clinical trial of suvecaltamide, an oral treatment candidate from Jazz Pharmaceuticals.
The Phase 2 trial (NCT05642442), which enrolled its first participant late last year, seeks about 160 adults, ages 40-80, with Parkinson’s who have moderate to severe tremors that interfere with daily life and medications are not controlling. The study is recruiting at several sites in the U.S.
“With the initiation of multiple clinical trials in 2022, we continue to expand our pipeline into disease areas with significant unmet patient need and market potential, including … Parkinson’s disease tremor,” Rob Iannone, MD, executive vice president and global head of research and development at Jazz, said in a company press release.
Tremors are a common motor symptom of Parkinson’s disease. A type of involuntary, uncontrollable muscle contraction, tremors can manifest as shaking, most often in the hands.
While disease treatments can help control tremors, many patients still have them and can significantly disrupt their ability to perform daily activities.
Parkinson’s patients show electrical activity changes in brain regions important for movement. These changes result in bursts of abnormal nerve cell activity that may be driving tremors.
Suvecaltamide’s effect on Parkinson’s-related tremor, essential tremor
T-type calcium channels may in part underlie these electrical aberrations. These channels are present on nerve cells where they mediate the influx of calcium, which makes it easier for a nerve cell to fire an electrical signal.
Suvecaltamide, previously known as JZP385 or CX-8998, is an orally available small molecule that works by selectively blocking T-type calcium channels. It was originally developed by Cavion, which was acquired by Jazz in 2019.
By reducing the activity of these channels, suvecaltamide is expected to ease tremors in patients and in people with essential tremor, a more common condition marked by tremors that are not secondary to a neurological disease.
A previous proof-of-concept trial (NCT03101241) found that twice-daily suvecaltamide was safe and improved some aspects of the condition in people with essential tremor. A follow-up Phase 2b trial (NCT05122650) is evaluating a once-daily formulation in this population.
In the Phase 2 trial for Parkinson’s-associated tremors, eligible patients must have been diagnosed with the neurodegenerative disease within the past five years and have moderate to severe impairments associated with tremors, as assessed by The Essential Tremor Assessment Rating Scale (TETRAS).
Participants must be on an optimized treatment regimen for their other symptoms. Dosing regimens for motor symptoms, including tremors, or lack of such treatments must have been stable for at least six weeks.
Following a screening period up to four weeks, participants will be randomly assigned to receive oral capsules of either suvecaltamide (10 mg) or a placebo, daily for 17 weeks (or nearly four months), followed by a two-week safety follow-up.
The first five weeks of the treatment period will involve dose optimization, during which the dose can be increased by 10 mg up to 30 mg daily, depending on its effectiveness and tolerability. The most effective dose will then be used for the remaining 12 weeks, or about three months, of treatment.
The trial’s main goal is to assess changes in tremor severity, as assessed by TETRAS composite outcome scores, which account for patient-rated impacts of tremors on daily functioning, as well as clinical evaluations of tremor severity. Other clinician and patient-reported outcomes will be assessed, as will changes in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale-tremor score.
Top-line data are expected in the first half of 2024.