Phase II Narcolepsy Clinical Trial Halted After Severe Adverse Effects

According to a story from Clinical Trials Arena, the pharmaceutical company Takeda recently released findings from its phase II clinical trial. This trial was evaluating the company’s investigational drug TAK-994 as a treatment for patients with type 1 narcolepsy, a rare sleep disorder. While the drug showed some benefit for treating symptoms of the disease, the company opted to halt the trial due to adverse effects, including hepatotoxicity that was observed in some patients.

About Narcolepsy

Narcolepsy is a neurological disorder that affects sleep. Patients with narcolepsy have a decreased ability to regulate their cycles of sleeping and wakefulness. The exact cause of narcolepsy is not well known. There are a number of risk factors for the condition however, such as family history, exposure to pesticides, or prior brain injury, such as a stroke or tumor. The most well-known symptom of narcolepsy is excessive sleepiness during the day, often to the extent that a patient may fall asleep suddenly during their regular activities. This can occur even after a full night of sleep; patients are unable to sleep as deeply as an unaffected person. Other symptoms include cataplexy, hallucinations, sleep paralysis, insomnia, and unexpected weight gain. There is no cure for narcolepsy. Treatments for the condition include stimulants such as amphetamines, sodium oxybate, and modafinil. Most patients cannot control their symptoms entirely. To learn more about narcolepsy, click here.

The Trials and its Findings

TAK-994 is classified as orexin receptor 2 (OX2R) agonist and was evaluated in adults with narcolepsy type 1 between age 18-65. Patients received either a placebo or a dose of the drug in 30mg, 90mg, or 180mg twice per day. The primary endpoint was variation in minute-based mean sleep latency over the course of eight weeks. This was evaluated using the Maintenance of Wakefulness test. Secondary endpoints included Epworth Sleepiness Scale score, treatment-emergent adverse events, and weekly cataplexy rate.

While the treatment produced significant effects, such as an increase in wakefulness during the day, and reduction or elimination in weekly cataplexy, adverse effects appeared in 79% of patients. The most common was frequent and urgent urination, but several patients experienced liver toxicity, resulting on the decision to halt the study.

The researchers noted the potential of the OX2R mechanism as a treatment target in narcolepsy type 1.

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