e-Therapeutics, a drug discovery and development company, reported top-line results for its phase IIb trial of ETS6103 in major depressive disorder evaluating its antidepressant activity and tolerance profile.
The trial evaluated dosing of ETS6103 as a potential second-line therapy for patients with major depressive disorder who do not respond satisfactorily or relapse when using the current first-line treatment, selective serotonin reuptake inhibitor (SSRI). The trial's aims were specially to determine whether ETS6103 is an antidepressant capable of treating the patients for whom SSRI treatment has not been successful, at a dose consistent with both improved compliance and a protectable position, with a more benign side effect and tolerance profile than a tricyclic, such as amitriptyline. The earlier phase IIa trial had shown a surprisingly strong efficacy position for ETS6103 with respect to amitriptyline, and the phase IIb trial was structured as a non-inferiority study.
The randomized, double-blind non-inferiority study was conducted in Glasgow on behalf of e-Therapeutics. The study enrolled a total of 383 patients into the trial. One hundred sixty-four patients who did not respond adequately to the first-line SSRI treatment were then randomized into one of three study arms, which included two doses of ETS6103 and one of amitriptyline. Patients were dosed over an eight-week treatment period.
As regards efficacy alone, the ETS6103 arms did not meet the primary endpoint of establishing non-inferiority when compared to amitriptyline. Specifically, while many patients responded to ETS6103, fewer achieved remission (as defined in the protocol: The Montgomery-Asberg Depression Rating Scale (MADRS) score below 11) than on amitriptyline. Responses were, however, observed in all three experimental arms of the study. In the two ETS6103 arms, some patients went into remission and there were fewer adverse event and side effect dropouts in the ETS6103 groups compared to amitriptyline.