Phase 2 trial of montelukast oral film approved in Sweden

Study will probe high dose on progression of early to moderate Parkinson’s

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by Andrea Lobo |

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IntelGenx has won approval from the Swedish Medical Products Agency (MPA) to conduct a Phase 2 trial on Montelukast Versafilm, its proprietary oral thin film formulation, in people with Parkinson’s disease.

The Phase 2 MONTPARK multicenter study will investigate the effectiveness of oral high-dose Montelukast on the progression of early to moderate Parkinson’s disease. The trial is expected to begin recruiting patients in the first quarter of 2024.

The study will be led by Per Svenningsson, MD, PhD, a Parkinson’s expert, at the Karolinska University Hospital and three other Swedish University affiliated institutions, under a previously announced research collaboration.

“We are delighted that this trial has been approved by the MPA and look forward to beginning patient recruitment as soon as possible,” Dwight Gorham, IntelGenx’s CEO, said in a company press release.

Parkinson’s is caused by the dysfunction and death of dopamine-producing nerve cells, or neurons, in a brain region called the substantia nigra. Dopamine is a major brain chemical messenger, essential for muscle control.

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Crossing the blood-brain barrier

Standard treatments for Parkinson’s motor symptoms include levodopa, a precursor of dopamine, to increase its levels in the brain. No neuroprotective or disease-modifying treatments are available, however.

Excessive inflammation has also been implicated in Parkinson’s and other neurological disorders, and contribute to neuron degeneration. Several studies in animal models and patients suggest modulating the immune system may be a potential therapeutic strategy for these conditions.

Montelukast, sold as Singulair and with generics available, blocks the cysteinyl leukotriene receptor 1, a mediator of inflammation. It’s commonly used to treat asthma and allergies and is available as oral and chewable tablets, and oral granules.

The therapy can cross the blood-brain barrier, the highly selective permeable membrane that prevents harmful molecules from entering the brain and spinal cord. This is an essential feature for therapies that aim to treat neurological diseases that target the brain or spinal cord.

An oral film formulation

IntelGenx has developed an oral thin film formulation using the company’s proprietary VersaFilm technology. It consists of a thin film applied in the mouth, providing several benefits over oral tablets, such as easy administration that doesn’t require water and direct absorption in the mouth.

This allows higher levels of the medication to reach target sites with reduced toxicity because it bypasses the body’s initial clearance of the digestive system and liver before making its way to the target site.

In a Phase 1 study, Montelukast VersaFilm was found safe and well tolerated in healthy people and showed a 52% higher bioavailability over oral tablets.

In a clinical trial (EudraCT 2020-000148-76) of 15 people with Parkinson’s conducted by Svenningsson’s team, montelukast oral tablets were found safe and well tolerated. The treatment was given twice daily, at a total daily dose of 40 mg, for three months.

“Montelukast VersaFilm [is] a more attractive dosing method due to its increased bioavailability (approximately 50% improvement over tablets) and minimizing the need on a daily basis for the requirement of numerous 10 mg Montelukast tablets,” Gorham said.

The MONTPARK trial will enroll up to 90 people with Parkinson’s who will be randomly assigned to receive either 30 mg Montelukast VersaFilm or a placebo film, twice daily for 18 months (about 1.5 years), for a total daily dose of 60 mg. This will be followed by a three-month washout period, where patients are taken off the medication to allow its effects to be eliminated.

Eligible patients must be receiving levodopa and can be on other dopaminergic treatments at their enrollment.

“We are excited to be collaborating with [Professor] Svenningsson … who previously demonstrated the safety and tolerability of 40 mg Montelukast in [people with Parkinson’s disease],” Gorham said. “Our study teams are quite eager and ready to commence the study with the novel IntelGenx Montelukast VersaFilm due to the beneficial features of the film in terms of ease of use, better compliance and bioavailability.”

Svenningsson is both the trial’s principal investigator and its sponsor, through a 20 million Swedish Crowns grant (about $2 million) awarded by the Swedish Research Council, a governmental research funding body.