Results from the AMBLED trial
A phase 2 trial of an experimental drug that aimed to treat the motor symptoms of Parkinson’s and reduce side effects of levodopa has shown disappointing results.
Most treatments for Parkinson’s work to mimic or replace dopamine, a chemical messenger that those with the condition are lacking. The most commonly used medication for Parkinson’s, levodopa, works in this way. But while there are many ways this medication has been improved over the years, levodopa cannot always fully manage symptoms and can cause troublesome side effects.
Side effects of Parkinson’s medication
As the symptoms of Parkinson’s progress, people may experience wearing off of their medication before the next dose is taken. During these times people may feel particularly stiff and slow. As well as this, people may experience dyskinesia: involuntary muscle movements including twitching and jerking.
Read more about dyskinesia and wearing off.
The AMBLED trial, run by Lundbeck, a global pharmaceutical company that specialises in brain conditions, set out to address these vital limitations of levodopa.
What did the trial involve?
The AMBLED trial aimed to investigate a drug called Foliglurax, also known as PXT002331. Back in 2016, this drug was shown to be safe and well tolerated in people without Parkinson’s. And the latest stage of the study involved testing the drug in people with Parkinson’s for the first time.
The study took place at 46 sites across 6 European countries, including the UK. It recruited 157 people who were taking levodopa, had been diagnosed with Parkinson’s for more than 3 years, and experienced wearing off and dyskinesia. These participants were randomly assigned to receive either a low or high dose of the experimental treatment or a placebo (dummy drug). They took this twice a day for a month alongside their levodopa medication.
How does Foliglurax work?
In Parkinson’s, levels of the chemical messenger glutamate are altered as the brain tries to compensate for the lack of dopamine. Excessive activity related to glutamate is believed to play a role in why some experience levodopa-induced dyskinesia. Foliglurax has been developed to reduce glutamate signalling and rebalance the brain.
There is already an approved drug that reduces glutamate signalling which can be prescribed to treat Parkinson’s symptoms: amantadine. In the UK, amantadine is normally prescribed with other Parkinson’s medications to treat tremor and rigidity. While helpful, it can have side effects and does not work for everyone.
The results
Unfortunately, Lundbeck has announced that the results from the phase 2 trial of Foliglurax in people with Parkinson’s failed to show sufficient beneficial effects. Those receiving the active drug treatment had no significant reduction in 'off' time compared to the placebo group. Foliglurax also failed to improve dyskinesia.
What’s next?
A publication of the full results of the AMBLED trial will follow this initial announcement. Whilst these results are disappointing there are other drugs being investigated to help with the side effects of levodopa. Indeed, one promising drug, called NLX-112, has recently been shown to reduce dyskinesia in people in an early phase clinical trial. It is hoped that this drug will enter clinical trials by the end of 2020.
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