A joint venture between HMNC Brain Health and Develco Pharma in Switzerland, Ketabon GmbH recently released top-line results from its phase 2 KET01-02 study of KET01, a slow-release formulation of oral ketamine, for treatment-resistant depression (TRD). KET01 was associated with improvements in depression severity as early as day 1, but the results were not statistically significant at day 21.
The promise of rapid onset without dissociative effects
“This is the second study with KET01 that demonstrates a signal of robust and rapid onset of improvement of depressive symptoms from baseline, without the prominent dissociative effects that have limited the uptake of other ketamine-based treatments,” stated Dr. Hans Eriksson, chief medical officer at Ketabon and HMNC Brain Health.
He added that conducting the KET01-02 study at home without concerns about administration further bolsters their take-at-home approach.
Regarding the lack of statistical significance at day 21 of the study, Eriksson said, “The important finding for the continued development of KET01 was the rapid improvement in depressive symptoms.”
The transient improvement in the placebo arm at week 3 “probably reflects the variability in placebo effects seen in smaller clinical trials, especially in depression studies with approximately 40 patients per treatment arm,” Eriksson said. “It was our choice to select day 21 as the primary efficacy time point, and if we instead had chosen the alternative of day 7, the study would have been positive, based on the same data set. This is not an attempt to “explain away” the lack of statistical significance at day 21, but it highlights the impact of random effects in smaller clinical trials.”
Ketabon KET01 treatment-resistant depression: A potential at-home optionMore data from the study are forthcoming. At present, Ketabon is focused on topline data showing potential for KET01 to be a take-at-home, oral ketamine option for patients suffering from TRD.
Patients in the study received either 120 mg/day KET01, 240 mg/day KET01, or a daily placebo, alongside their regular antidepressant regimen for three weeks.
On the topic of dosage selection for KET01, Ketabon selected the doses for the KET01 program based on “’back-calculating’ from the established efficacious dose of 0.5 mg/kg when ketamine is administered intravenously,” Eriksson shared. The conversion required considering the lower oral bioavailability and pharmacokinetic data with oral ketamine relative to intravenous.
“The 240 mg/day KET01 dose did show a signal of antidepressant efficacy in a previous smaller Phase 2 trial of adjunctive treatment in treatment-resistant depression (TRD), KET01-01, with a MADRS mean score separation from placebo of about 5 points after 2 weeks,” Eriksson added. In that earlier study, the total daily dose was divided into two 120 mg doses, with one taken in the morning, and another in the evening.
“These findings encouraged us to use a daily dose of 240 mg in the larger KET01-02 study. In KET01-02, we administered the entire dose in the morning, thereby achieving somewhat higher peak concentrations of ketamine, but a similar overall daily exposure,” Eriksson said. “The fact that we now have seen a signal of antidepressant efficacy with a dose of 240 mg/day in two studies in TRD will encourage us to use this dose as a benchmark to include in future studies. The 120 mg/day dose was selected to identify a lower, potentially efficacious dose, but in the KET01-02 trial, it was only marginally numerically better than placebo.”
Filed Under: clinical trials, Drug Discovery and Development, Psychiatric/psychotropic drugs