It seems that there have been some significant gastro-intestinal (GI) problems in the Alzheimers trials for Encenicline in the current phase three clinical trials. I wonder if the issue is related to the age of the patients in the trial - something that would not be an issue with most people who have schizophrenia (because they are much younger). We’ll see when more information is announced.
Two fully enrolled Phase 3 efficacy trials evaluating the use of encenicline to treat CIS will continue, with additional vigilance around GI safety monitoring of patients. Top-line results from these trials are anticipated in the first half of 2016.
FORUM was advised that studies investigating the use of encenicline in Alzheimer’s disease (AD) have been placed on clinical hold. A small number of serious gastrointestinal (GI) safety events reported in the AD studies prompted the clinical hold. FORUM has discontinued all study medication in the AD trials and no new patients will be recruited into the studies until the clinical hold is lifted.
Representatives at FORUM Pharmaceuticals would not elaborate on the details of the gastrointestinal symptoms, including whether the symptoms were dose-related or occurred more frequently in the treatment groups. The Phase 3 studies included a higher dose—3 mg—than did the Phase 2 study. The severe symptoms occurred in a small number of patients and were somewhat variable in their presentation, wrote Priscilla Harlan, a communications consultant at the company, in an email to Alzforum. “It is worth bearing in mind that most Alzheimer’s disease patients are elderly, many with co-morbid conditions and receiving concomitant medications, many of which are themselves associated with a GI risk for this patient population,” she added. “AD patients are known to have a higher risk of GI adverse events than do elderly patients without AD.” Harlan added that the company is investigating the potential causes of the GI events, and the extent to which the drug played a role.
EVP-6124 is being tested in Phase 3 in schizophrenia patients as well. Two of these ongoing trials are fully enrolled (see clinicaltrials.gov, and trial); the third is still recruiting (see clinicaltrials.gov). The FDA has stipulated that the two enrolled trials, which are efficacy trials, can continue, while they put the newest trial, a safety extension, on hold. FORUM Pharmaceuticals declined to comment on the reason for this hold. Harlan noted that none of the more than 1,500 schizophrenia patients enrolled in the trials have experienced severe gastrointestinal symptoms. This could be due to their younger age, which averages 35 to 40 years, compared to the average age of 75 in the AD trials, Harlan said. She said that patients who remain in the ongoing trials will be monitored closely for GI events.