Winston-Salem, N.C. — Targacept, Inc. has announced top-line results from a Phase 2 proof of concept trial of TC-5619 as a treatment for adults with attention deficit/hyperactivity disorder (ADHD).
In the trial, conducted in non-smokers, TC-5619 did not meet the primary efficacy outcome measure, change from baseline on the Conners’ Adult ADHD Rating Scale-Investigator Rated Total ADHD Symptoms score (CAARS-INV) after four, eight and 12 weeks of dosing. Targacept announced positive top-line results from a separate Phase 2 trial of TC-5619 in cognitive dysfunction in schizophrenia (CDS) in January. TC-5619, a highly selective alpha7 neuronal nicotinic receptor modulator, is subject to license by Targacept’s strategic collaborator AstraZeneca, with a decision expected in the second quarter of 2011.
The ADHD trial included a number of scales and assessments as secondary efficacy outcome measures. The results across all of these assessments indicate that TC-5619 had activity in this patient population, with TC-5619 outperforming placebo with statistical significance (as defined by the protocol, one-sided p-value < 0.10) approximately seven times more often than placebo outperformed TC-5619 by the same standard.
TC-5619 performed best on the Conners’ Adult ADHD Rating Scale-Subject Rated (CAARS-S), a patient self-rating scale, where the results favored TC-5619 with statistical significance (one-sided p-value < 0.10) on four of five subscales at 12 weeks.
TC-5619 was generally well tolerated in the trial, with no serious adverse events reported and no clinically significant difference between the TC-5619 dose group and the placebo dose group in discontinuations due to adverse events. Adverse events reported in at least five percent of patients in the TC-5619 dose group and at least twice as often as in the placebo dose group included headache (9 percent), rash (6 percent; resolved during treatment phase) and somnolence (6 percent).
“We continue to pursue a strategy of using initial Phase 2 development to gain clinical insights that help identify the indications for which our compounds will be best suited for later-stage development,” said J. Donald deBethizy, PhD, Targacept’s president and CEO.
“While we did not see stimulant-like efficacy in this learning trial, the overall findings provide additional evidence that TC-5619 is active in a cognitively-impaired patient population, with the safety results adding to an impressive profile for a compound that has now been studied in more than 200 subjects," added deBethizy.
"Coupled with positive outcomes from our prior Phase 2 study in patients with schizophrenia on measures of executive function, negative symptoms of schizophrenia and global change, we now have a foundation to guide future development of TC-5619.”
Analyses of the full dataset from the ADHD trial are ongoing, and Targacept plans to present more detailed results at a future scientific meeting.
In addition to its completed Phase 2 trials in CDS and ADHD, Targacept is currently conducting clinical and non-clinical studies designed to support potential Phase 2 development of TC-5619 in a third indication with high unmet medical need, Alzheimer’s disease.
The double blind, placebo controlled, forced titration Phase 2 trial was conducted at 17 sites in the United States. In the trial, 135 non-tobacco using patients, age 18 to 65 and meeting DSM-IV criteria for ADHD, were randomized to receive either TC-5619 or placebo for 12 weeks.
Approximately 58 percent of randomized patients were male. Patients randomized to the TC-5619 dose group received a 1mg daily dose for the first four weeks, a 5mg daily dose for the next four weeks and a 25mg daily dose for the last four weeks.
There was an approximately 38 percent dropout rate in the trial, resulting in 84 patients completing. The primary efficacy outcome measure was change from baseline on CAARS-INV after four, eight and 12 weeks of dosing, as compared to placebo. The trial also included a number of other scales and assessments as secondary efficacy outcome measures.