Promising Preliminary Results for Drug to Treat Cognitive Dysfunction Associated With Schizophrenia

Targecept has recently announced positive results in their Phase 2 clinical trial to evaluate the new drug TC-5619′s ability to improve cognition in patients with schizophrenia.

Many see schizophrenia, a devastating brain disorder, as an illness that causes hallucinations, paranoia, and delusions. However, the disease is also characterized by cognitive deficits that cause an inability to think, learn, remember, and concentrate. More than 2 million in the US suffer from schizophrenia, and 75% of these experience cognitive dysfunction.

Cognitive deficits associated with schizophrenia have a significant impact on a person’s ability to function at home, work, and school. Many medications are available to treat the hallucinations and delusions, but there is currently no medication available to treat cognitive dysfunction from schizophrenia.

Targacept has been working to develop medications that meet this need. Their latest product, TC-5619, binds the alpha-7 neuronal nicotinic receptor (NNR), which is involved in normal cognitive brain function.

The multi-center Phase 2 clinical proof of concept trial is a double-blind, placebo-controlled, randomized, parallel group study conducted at seven sites in the United States and twelve sites in India. Nearly 200 patients diagnosed with schizophrenia and taking either the antipsychotic, quetiapine (Seroquel®) or risperidone (Risperdal®) were enrolled in the study.

Volunteers were randomly assigned to receive either TC-5619 or placebo together with their prescribed antipsychotic for 12 weeks. Patients receiving TC-5619 were administered 1 mg daily dose for the first four weeks, 5 mg daily for the next four weeks, and 25 mg daily dose for the last four weeks. Before the study started, patients from both groups were given the GMLT (Groton Maze Learning Test), a computerized assessment of their cognitive function.

This test was then administered at three separate times during the course of the 12 week treatment period. Study investigators looked for a change in patients’ GMLT scores from baseline.

TC-5619 was considered superior to placebo if their was an improvement in GMLT scores following treatment and that improvement was significantly different from the GMLT scores observed with placebo. Not only did the study see improvement in GMLT scores with TC-5619, but these improvements were noted at two of the three measurement dates (at 4 weeks and 12 weeks).

There were no differences in adverse events associated with placebo and TC-5619. The most frequent adverse event was mild to moderate nausea (5%); this nausea did not cause patients to dropout of the study. Targacept plans to release detailed information about study results later this year.

There are a wide number of other therapies and treatment regimens being evaluated to improve the quality of life for people suffering from schizophrenia.