Clinical Trials

* On February 15, 2016, e-Therapeutics, the drug discovery and development company, reports 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 randomised, 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. 164 patients who did not respond adequately to the first-line SSRI treatment were then randomised 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: 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. e-Therapeutics said that, while ETS6103, in common with almost all other antidepressants, was not non-inferior to amitriptyline in efficacy terms, the results overall are pleasingly similar to the profile of ETS6103 that the company hoped to have. Further analysis of the data is being undertaken and a fuller update will be provided at the preliminary results, due in March.

* On October 31, 2013, e-Therapeutics has announced that it has started a randomised double-blind controlled phase IIb trial of ETS6103 in major depressive disorder. The trial is evaluating ETS6103 as a second-line treatment for patients who have not responded adequately to first-line therapy with an SSRI (selective serotonin reuptake inhibitor). It is being conducted by a group of primary care centres with a history of involvement in depression studies in the Glasgow area of Scotland. Under the trial protocol, patients are enrolled prior to first-line treatment so that this can be standardised: every patient will receive the SSRI citalopram. Those with significant depressive symptoms remaining after six weeks on citalopram will enter the randomised phase of the study, which compares two different doses of ETS6103 with amitriptyline, a widely available tricyclic antidepressant. Approximately 160 patients will be randomised.

The principal objective is to test whether the two ETS6103 regimens have antidepressant activity ’non-inferior’ to that of amitriptyline. The primary measure of activity is the change in Montgomery–Åsberg Depression Rating Scale (MADRS) score between randomisation and the end of treatment eight weeks later. Safety and a variety of secondary efficacy variables will also be assessed. e-Therapeutics expects to report the results of the trial in the first half of 2015. If these are positive, the Company intends to seek a licensing deal for the drug.