Weekly Risperidone capsule provides consistent drug levels for schizophrenia patients

Weekly Risperidone capsule provides consistent drug levels for schizophrenia patients

Many patients with schizophrenia, other psychiatric illnesses, or illnesses such as high blood pressure and asthma can find it difficult to take their medicine every day. To overcome this challenge, MIT researchers have developed a pill that can be taken just once a week and gradually releases medication from the stomach.

In a Phase 3 clinical trial conducted by MIT spinout Lyndra Therapeutics, researchers used the once-weekly pill to deliver a widely used drug to treat the symptoms of schizophrenia. They found that this treatment regimen maintained consistent levels of the drug in patients' bodies and controlled their symptoms as well as daily doses of the drug. The results will be published today inLancet Psychiatry.

“We converted something that needs to be taken once a day to once a week, using technology that can be adapted for a variety of medications,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women's Hospital, an associate member of the Broad Institute and an author of the study. “The ability to provide a sustained level of medication for a longer period of time makes it easier to ensure that patients receive their medications.”

Traverso's lab began developing the ingested capsule studied in this study more than 10 years ago to make medication easier for patients. The capsule is about the size of a multivitamin and expands into a star shape when swallowed, helping it stay in the stomach until all of the medication is released.

Richard Scranton, chief medical officer of Lyndra Therapeutics, is senior author of the paper, and Leslie Citrome, a clinical professor of psychiatry and behavioral sciences at New York Medical College School of Medicine, is the lead author. Nayana Nagaraj, medical director at Lyndra Therapeutics, and Todd Dumas, senior director of pharmacometrics at Certara, are also authors.

Sustained delivery

Over the past decade, Traverso's lab has been working on a variety of capsules that can remain in the digestive tract for days or weeks, slowly releasing their drug payload. In 2016, his team reported the star-shaped device, which was then further developed by Lyndra for clinical trials in patients with schizophrenia.

The device contains six arms that can be obsolete, allowing it to fit into a capsule. The capsule dissolves when the device reaches the stomach and the arms pop out. Once the arms are expanded, the device becomes too large to pass through the pylorus (the exit of the stomach), so it floats freely in the stomach as medication is slowly released from the arms. After about a week, the arms break off on their own, and each segment leaves the stomach and exits the digestive tract.

For the clinical trials, the capsule was loaded with risperidone, a commonly prescribed medication to treat schizophrenia. Most patients take the medication orally once a day. There are also injectable versions that can be administered every two weeks, every month, or bimonthly. However, they require administration by a healthcare provider and are not always acceptable to patients.

The MIT and Lyndra team decided to focus on schizophrenia in the hope that a drug regimen that could be administered less frequently through oral delivery would make treatment easier for patients and their caregivers.

One of the areas of unmet need identified early is neuropsychiatric conditions in which the illness limits or impairs the ability to remember to take their medications. With that in mind, one of the conditions that was a big focus was schizophrenia. “

Giovanni Traverso, associate professor of mechanical engineering at MIT

The Phase 3 study was coordinated by Lyndra researchers and included 83 patients at five different sites in the United States. Forty-five of these patients completed the full five weeks of the study, during which they took one risperidone-loaded capsule.

Throughout the study, researchers measured the amount of drug in each patient's bloodstream. Each week they found a sharp increase on the day the pill was given, followed by a slow decrease the next week. The values ​​were all within the optimal range, and there were fewer variations over time than if patients took a pill daily.

Effective treatment

Using a score known as the Positive and Negative Syndrome Scale (PANSS), researchers also found that patients' symptoms remained stable throughout the study.

"One of the biggest barriers to caring for people with chronic illnesses in general is that medications are not taken consistently. This leads to worsening symptoms and, in the case of schizophrenia, potential relapse and hospitalization," says Citrom. “The ability to take medications by mouth once a week represents an important option that may aid compliance for the many patients who prefer oral medications over injectable formulations.”

Side effects of the treatment were minimal, the researchers found. Some patients had mild acid reflux and constipation early in the study, but these did not last long. The results, showing the capsule's effectiveness and few side effects, represent an important milestone in this drug delivery approach, says Traverso.

“This really shows that what we suspected a decade ago, that a single capsule delivering a drug depot within the GI tract, could be possible,” he says. “Here you can see that the capsule achieves predicted drug levels and also controls symptoms in a significant cohort of patients with schizophrenia.”

Investigators now hope to conduct larger Phase 3 trials before applying for FDA approval of this delivery approach to risperidone. They are also preparing for Phase 1 trials that use this capsule to deliver other medicines, including contraceptives.

“We are pleased that this technology, which began at MIT, has reached the point of Phase 3 clinical trials,” says Robert Langer, the David H. Koch Professor at MIT, who was an author of the original Star capsule study and is co-founder of Lynndra Therapeutics.

The research was funded by Lyndra Therapeutics.

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