Inbrija (CVT-301)

Inbrija (CVT-301) is an inhaled formulation of levodopa developed by Acorda Therapeutics. It is approved by the U.S. Food and Drug Administration (FDA) to treat symptoms of Parkinson’s disease during off episodes, periods of time when levodopa treatments stop working and motor symptoms return.

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 symptoms such as the lack of motor control.

Dopamine cannot be directly administered because it cannot cross the blood-brain barrier, a semipermeable membrane that surrounds the brain and spinal cord to protect them from the outside environment.

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 nerve-cell signaling.

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.

Inbrija is a 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 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 is expected to deliver a more reliable dose of medication and start working faster than the oral form of the medication.

Inbrija in trials for Parkinson’s

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 2017. The double-blind, randomized trial assessed the safety and effectiveness of Inbrija in treating off episodes compared with a placebo in 351 participants with Parkinson’s.

The results demonstrated that patients taking 84 milligrams (mg) of Inbrija had significantly improved motor function compared with those in the placebo group.

Acorda has also completed two Phase 3 trials that assessed the long-term safety of Inbrija.

One trial (NCT02352363) evaluated changes in lung function in 408 Parkinson’s patients. Individuals were given either 84 mg of Inbrija up to five times daily together with standard of care, or standard of care alone. The results showed no significant difference between the treatment and control groups, suggesting that Inbrija does not affect lung function.

This trial also found that Inbrija decreased Parkinson’s-related symptoms when standard treatment wears off, and it reduced the length of off periods.

Another trial (NCT02242487) enrolled 325 patients who completed the SPAN-PD trial, with the aim of assessing the long-term safety of both low (60 mg) and high (84 mg) doses of Inbrija for a further year. 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 study (NCT03887884) enrolled 23 patients with Parkinson’s disease to assess Inbrija’s pharmacokinetics (how quickly a treatment reaches the bloodstream and how quickly it is metabolized) in patients who regularly took oral carbidopa/levodopa.

The study found that Inbrija was more rapidly absorbed than oral carbidopa/levodopa. Inbrija absorption also was less variable among patients compared with the other treatment. According to this study, Inbrija can be used regardless of food intake.

Other information

Two Inbrija capsules of 84 mg can be taken up to five times a day to treat off episodes. The maximum dose per off episode is 84 mg, and the maximum recommended daily dose is 420 mg.

Inbrija should be taken only using the Inbrija inhaler.

The treatment may cause serious side effects, such as body pain, chills, cough, nausea, and breathing problems, and it is not recommended for those with asthma, chronic obstructive pulmonary disease, or other chronic underlying lung disease.

Hallucinations or psychosis may also occur, and patients with a major psychotic disorder should not be treated with Inbrija.

The treatment may also cause or exacerbate dyskinesia — uncontrolled, involuntary movements.

Inbrija is contraindicated in patients who are taking nonselective monoamine oxidase (MAO) inhibitors or who have recently (within two weeks) taken this medication.

Additional information can be found on the therapy’s label.

 Last updated: Dec. 15, 2021, by Teresa Carvalho MSc

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