Med Check: FDA COVID-19, FDA Electrical Stimulation Devices, Montelukat Warning, FDA NDA Zolmitriptan, Deutetrabenazine Fails Trials

The Food and Drug Administration (FDA) in March issued guidance for researchers conducting clinical trials during the coronavirus (COVID-19) pandemic.

“Although the impact of COVID-19 on trials will vary depending on many factors, including the nature of disease under study, the trial design, and in what region(s) the study is being conducted, the FDA outlines considerations to assist [trial] sponsors in ensuring the safety of trial participants, maintaining compliance with good clinical practice, and minimizing risks to trial integrity,” the agency stated in a press release.

Such considerations include evaluating whether in-person visits are necessary to fully assure the safety of trial participants or whether alternative methods for assessments, such as phone calls or virtual visits, can be made. Other considerations include offering additional safety monitoring for trial participants who may no longer have access to an investigational product (for example, withdrawal of an active medication) or the investigational site.

“With this guidance issued today, the FDA is helping industry and investigators navigate the COVID-19 pandemic and help assess how to move orward with critical clinical trials,” said Anand Shah, M.D., FDA deputy commissioner for medical and scientific affairs. “The FDA released this guidance to emphasize that at all times, patients’ safety should continue to be at the forefront of considerations.”

In March the FDA published a final rule banning electrical stimulation devices (ESDs) used for self-injurious or aggressive behavior, declaring in a statement that the devices “present an unreasonable and substantial risk of illness or injury that cannot be corrected or eliminated through new or updated device labeling.”

The agency noted that several significant psychological and physical risks are associated with the use of these devices, including worsening of underlying symptoms, depression, anxiety, posttraumatic stress disorder, pain, burns, and tissue damage. In addition, many people who are exposed to these devices have intellectual or developmental disabilities that make it difficult to communicate their pain.

The ban is a finalization of a 2016 proposed rule and applies only to ESDs used to control self-injurious or aggressive behavior. It does not apply to aversive conditioning devices used for other purposes, such as those used for smoking cessation, or to FDA-cleared or approved technologies, such as cranial electrotherapy stimulators or transcranial magnetic stimulation.

According to the FDA, at the time of the announcement regarding the ban, it appeared that only one facility in the United States used ESDs, the Judge Rotenberg Educational Center in Canton, Mass., where between 45 and 50 individuals had been exposed to the devices.

The FDA is now requiring a boxed warning for montelukast, which is sold under the brand name Singular and in generic form to treat asthma and hay fever (allergic rhinitis). The boxed warning strengthens an existing warning about the risks of neuropsychiatric events with montelukast such as agitation, depression, sleep problems, and suicidal thoughts and actions, and it advises health professionals to avoid prescribing montelukast for patients with mild symptoms, particularly those with hay fever.

The FDA required the box warning after reviewing continued reports of suicide and other adverse events by patients taking the medication, including reports submitted through the agency’s Adverse Event Reporting System (FAERS) and studies published in the medical literature. The FDA had also conducted its own study using data in the Sentinel Distributed Database, which is generated from patient interactions in the United States health care system through their insurers and providers, and presented the findings at an FDA advisory committee meeting in 2019.

“Based upon this assessment, the FDA determined the risks of montelukast may outweigh the benefits in some patients, particularly when the symptoms of the disease are mild and can be adequately treated with alternative therapies. For allergic rhinitis in particular, the FDA has determined that montelukast should be reserved for patients who have not responded adequately to other therapies or who cannot tolerate these therapies,” the agency said in a March 4 Drug Safety Communication.

In March the FDA accepted a New Drug Application (NDA) for Qtrypta for the treatment of migraine. Qtrypta, manufactured by Zosano Pharma Corporation, delivers zolmitriptan through an intracutaneous microneedle system. The drug-coated microneedles are designed to penetrate the epidermis and dermis, where the drug dissolves and enters the bloodstream.

The ZOTRIP pivotal phase 2/3 clinical study evaluated the efficacy, safety, and tolerability of Qtrypta compared with placebo in 333 patients aged 18 to 65 years. Among those treated with a 3.8 mg dose of Qtrypta, 41.5% achieved freedom from migraine pain within two hours. In addition, 68.3% reported freedom from their most bothersome non-pain symptom within two hours, such as nausea, sensitivity to light, or sensitivity to sound.

In the phase 3 long-term safety study, the most frequently reported adverse event was redness at the application site. Fewer than 2% of patients reported neurological side effects typically found in the class, such as dizziness and paresthesia.

In February Teva Pharmaceutical Industries Ltd. announced that Austedo (deutetrabenazine) did not meet the primary endpoints of trials comparing the drug with placebo for the treatment of tics in pediatric patients with moderate to severe Tourette’s syndrome. Austedo is approved for the treatment of chorea associated with Huntington’s disease and tardive dyskinesia in adults.

The phase 2/3 ARTISTS 1 study evaluated the safety, tolerability, and efficacy of Austedo in 119 patients aged 6 to 16 years with moderate to severe Tourette’s syndrome. Patients received either deutetrabenazine or placebo for 12 weeks. The primary endpoint was the change in the total tic score on the Yale Global Tic Severity Scale (YGTSS) from baseline to week 12.

In the phase 3 ARTISTS 2 study, 158 patients aged 6 to 16 years with moderate to severe Tourette’s syndrome received either low-dose or high-dose Austedo or placebo over eight weeks. The primary endpoint was the change in the total tic score on the YGTSS from baseline to week eight in the placebo and active treatment groups. ■