Study Indicates Take-at-Home, Oral Ketamine is an Effective Option for Treatment-Resistant Depression

Ketabon, a dual venture between HMNC Brain Health and Develco Pharma, recently announced key findings from the phase 2 KET01-02 Ketabon study, which evaluated the use of oral ketamine for the treatment of depression. The trial investigated the efficacy, safety, and tolerability of KET01, an oral supplementary treatment using a prolonged-release formulation of ketamine, in 122 out-patients with treatment-resistant depression (TRD). These patients were unresponsive to the minimum of 2 standard antidepressants, therefore fulfilling the criteria for TRD.¹

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Over a 3-week period, study participants received either a 120 mg or 240 mg daily dose of KET01 or placebo in addition to their ongoing standard antidepressant treatment. The study was conducted across a total of 29 sites in Germany, Poland, and the Czech Republic.¹

At a 240 mg daily dose, KET01 demonstrated rapidly occurring and clinically relevant improvements in the severity of patients’ depression on days 4 and 7, compared to placebo. The improvements from baseline were continuous in the patients who received active treatment until day 21, with improvements continuing to be noticeable after the 4-week follow-up period. Further, the placebo-treated cohort had shown some improvement during the trial, and at day 21—the primary endpoint—the change from baseline in the 240 mg per day cohort did not match the statistical implication compared to placebo.¹

“KET01 offers rapid improvement of depressive symptoms while the occurrence of dissociative events interestingly seems to be lower than in currently used ketamine-based treatments. This could lead to wider and more convenient, private at-home use,” said the study’s international coordinating investigator Martin Walter, chair and head of the Department of Psychiatry and Psychotherapy of University Jena, in a press release.¹

Additionally, the antidepressant effects of KET01 were not associated with the usual findings of other ketamine-based treatments (e.g., increased dissociation, heart rate, and blood pressure) that have been a hinderance to clinical uptake of other ketamine- and esketamine-based TRD treatments.¹

“We are highly encouraged by the top-line results of KET01-02, which have the potential to transform the treatment landscape for patients continuing to suffer from TRD,” said Hans Eriksson, PhD, HMNC Brain Health's chief medical officer, in the press release.“Notably, these results were not associated with a signal of dissociative symptoms, as measured by the Clinician-Administered Dissociative States Scale, suggesting that the oral prolonged-release administration has the potential to be a robust antidepressant that offers better tolerability than other forms of ketamine-based treatments."¹

Previous research has demonstrated that other forms of ketamine including at-home sublingual, rapid dissolving tablets (RDT), have been effective at treating TRD. As few as 3 doses of RDT were found to improve patients’ moderate to severe depression, with 50% of the study’s participants showing improvement in depression and anxiety symptomology; however, only 60% of participants who took the clinically recommended 6 doses of ketamine had reported improved symptoms. Like KET01, RDT has been found to be a safe and effective treatment compared to less accessible forms of ketamine, such as intravenous (IV) infusions.²

Another study had determined that subcutaneous injections of ketamine were an effective method of treating TRD. Compared to fixed doses of treatment (0.5 mg/kg ketamine and 0.025 mg/kg midazolam), flexible response-guided dosing (0.5 mg/kg to 0.9 mg/kg ketamine and 0.03 mg/kg to 0.045 mg/kg midazolam) was noticeably more effective in treating TRD symptoms due to the gradual dosage increase as the trial progressed.³

Not only were the injections shown to be effective, but they were more affordable than IV and nasal spray formulations of ketamine. The S-ketamine nasal spray costs approximately $800 per dose, which is more expensive than $5 per ketamine injection (plus a $350 session fee). Because the effects of treatment can wear off over a few days to a week, ongoing treatment is a possibility, resulting in patients wanting to pursue a more cost-effective option.³

“TRD is a major medical problem affecting close to a hundred million people worldwide, and patients suffering from this condition currently have very limited treatment options. While ketamine has been shown to provide effective relief, it has been hampered by the high incidence of dissociative side effects and other adverse events, leading to the need for resource-intensive monitoring programs,” Walter said in the press release. “KET01 has the potential opportunity to vastly change this paradigm.”¹

References

1. Ketabon. Ketabon GMBH Reports Top-Line Results From Phase 2 Trial of Take-at-Home, Oral Ketamine Option for Treatment-Resistant Depression. News release. August 14, 2023. Accessed August 14, 2023. https://bit.ly/47vkEyS

2. Hunter, E. Sublingual Ketamine Demonstrated to Be Safe, Effective for Patients with Treatment-Resistant Depression. Pharmacy Times. https://bit.ly/3KHjwyp January 18, 2023. Accessed August 14, 2023.

3. McGovern, G. Double-Blind Trial Shows Low-Cost Subcutaneous Version of Ketamine is Effective Over Placebo in Treating Treatment-Resistant Depression. Pharmacy Times. https://bit.ly/457L9sO July 19, 2023. Accessed August 14, 2023.