Inbrija (CVT-301) is an inhaled formulation of levodopa developed by Acorda Therapeutics. Inbrija is approved by the U.S. Food and Drug Administration (FDA) to treat symptoms of Parkinson’s disease during so-called “off” episodes.
How Inbrija works
Parkinson’s disease is a progressive neurodegenerative disorder caused by the death of nerve cells in the brain, specifically, those that produce a neurotransmitter called dopamine. Neurotransmitters are chemical messengers that pass signals between nerve cells; dopamine is involved in signaling pathways for coordinating movement.
As nerve cells die, dopamine levels in the brain decrease and Parkinson’s patients experience a lack of motor control.
Levodopa therapy is prescribed to increase dopamine levels in the brain. Levodopa is a chemical that can pass through the blood-brain barrier. Once inside the brain, it is broken down into dopamine and improves signaling in the brain.
However, traditional tablet forms of levodopa may result in a variable dosage reaching the brain. This inconsistency is due to varying amounts of levodopa being absorbed in the digestive system and the high rate of clearance of levodopa from the bloodstream by digestive enzymes. This variable can contribute to off episodes as the medication wears off earlier than anticipated.
Inbrija is a new dry powder formulation of levodopa that, when inhaled, may bypass these issues and deliver a higher and more consistent dose of levodopa to the brain. Inbrija uses the ARCUS technology platform, a specialized hand-held inhaler, to deliver a high and precise dose of levodopa into the lungs, where it can be absorbed easily into the bloodstream. By avoiding the digestive system, Inbrija should deliver a more reliable dose of medication and start working faster than the oral form of the medication.
Inbrija in clinical trials
Inbrija has been the focus of several clinical trials in Parkinson’s disease.
Acorda announced positive results from one of these trials, the Phase 3 SPAN-PD trial (NCT02240030), in February 2017. The open-label, double-blind, randomized trial assessed the safety and effectiveness of Inbrija in treating off episodes compared to a placebo in a total of 339 participants with Parkinson’s at 74 locations in North America and Europe. The participants were assigned either a high (84 mg) or low (60 mg) dose of Inbrija or a placebo, to be self-administered up to five times a day in response to off episodes, for a total of three months. The trial assessed any improvements in motor function, the time it takes for the treatment to have an effect, and its safety.
The results, presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS), in June 2017 demonstrated that patients taking the high dose of Inbrija had significantly improved movements compared to those in the placebo group. Participants were assessed using the unified Parkinson’s disease rating scale (UPDRS)-part 3.
The first trial assessed any changes in lung function in 271 Parkinson’s disease patients given a high dose of Inbrija for up to five times daily for 12 months, compared to an observed group receiving standard of care. The results of the trial demonstrated no significant difference between the treatment and control groups, suggesting that Inbrija does not affect lung function.
The second trial enrolled patients who completed the SPAN-PD trial, with the aim of assessing the long-term safety of both the low and high doses of Inbrija for a further year. The trial enrolled 149 patients on high-dose and 146 on low-dose treatment. The safety profile was similar to previous trials. The most common side effects associated with Inbrija were cough, cold, involuntary muscle movements, and falls.
A Phase 1 clinical trial (NCT03887884) is currently recruiting 24 patients with Parkinson’s disease to assess Inbrija’s pharmacokinetics (how quickly the treatment reaches the bloodstream and how quickly it is metabolized) in patients who regularly take carbidopa/levodopa. On each of two treatment days, patients will eat a standard high-fat meal and receive either a single dose of Inbrija or a single dose of oral carbidopa/levodopa. A blood sample will be taken at intervals of four hours. The following day, patients will eat a meal, followed by the alternate treatment from the previous day. The study will be carried out in the U.S. at sites in California, Florida, Georgia, Michigan, and New Jersey, and is expected to be completed in August 2019.
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