Douglas Pharmaceuticals Ltd (Douglas), a privately held New Zealand-headquartered pharmaceutical company, today announced positive top-line data from its multinational, randomized, placebo-controlled, double-blind Phase 2 study of R-107 designed to investigate the efficacy and safety of R-107 (ketamine 30, 60, 120 or 180 mg) versus placebo for TRD. The study was carried out in New Zealand and Australia, Singapore, Taiwan, and 2021. 168 patients were randomized.
TRD can be defined as the absence of clinically meaningful improvement in depression despite adequate doses at least two antidepressant drugs, administered for a reasonable duration and with good treatment adherence. TRD patients have limited treatment options.
Participants were subject to an open-label enrichment phase for one week. They received R-107 open label 120 mg/day for five days. Double-blind placebo was given to those who showed improvement in depression. They were randomly assigned to receive R-107 open-label 120 mg/day for 5 days. Primary endpoint was the change in depression ratings, Montgomery-Asberg Depression Rating Scales (MADRS).
The enrichment phase saw 73% (168/231) TRD patients quickly remit (MADRS score =12 within one week of open-label R-107 120mg daily treatment). During the enrichment phase, the mean MADRS scores dropped from 31 to 13.
Primary efficacy analysis revealed that 180 mg dosage group had a statistically significant reduction in MADRS score of 6.1 points compared to the placebo group (p=0.019). The MADRS score reductions in the 30 mg, 60mg, and 120m mg groups were 1.9, 0.75, and 4.5 points, respectively, as compared with placebo. These differences were not statistically significant.
R-107 was generally well tolerated. Headache, dizziness, anxiety were the most frequent TEAEs in all dose groups (>10% overall). The study did not report any product-related Serious Adverse Events.
Douglas plans to begin Phase 3 study in 2022 using the best dosing protocol as confirmed by Phase 2 studies.
Douglas Chief Scientific Officer Dr Peter Surman commented that he saw a clear dose-response relationship from the efficacy data. This makes it possible to select the optimal dosing protocol in the Phase 3 study. We are excited to move R-107 development into pivotal trials thanks to the compelling data of the BEDROC trial. This includes both the speed and durability of the response. We thank all the investigators who participated in the study, particularly for adapting to the Covid-19 pandemic. We look forward in continuing R-107 development with the goal to bring a new, effective treatment for the millions of TRD patients.
Jeff Douglas, Douglas’ Managing Director, stated that R-107 has “cleinically meaningful efficacy” as an anti-depressant, making it an ideal therapy for those who have suffered from TRD for many years without any relief. The quick recovery of mood within one week is a major advantage over current treatments, which can take up to six weeks.
Professor Paul Glue MD, University of Otago Hazel Buckland Professor and Chair of the Trial Steering Committee at BEDROC said, “As a researcher and a clinician who treats many patients suffering from TRD, these data are really encouraging.” R-107’s rapid onset of treatment response and its excellent tolerability compared to other methods of ketamine dosing is especially impressive. R-107, if confirmed in pivotal studies, could have a major impact on the way we treat patients with TRD.
R-107Douglas has been developing R-107, an oral treatment for depression that is fast acting. Ketamine is an antagonist of the NMDA receptor. R-107 has been formulated to release ketamine slowly and steadily over 12 hours. This helps to minimize psychotomimetic side-effects that can be associated with other ketamine dosage forms.
Phase 2 BEDROC study key results
Average total MADRS change from Day 1 through Day 92 vs. placebo group
R-107 180 mg group: 6.1, p=0.019
R-107 120 mg group: 4.5, p=0.083
R-107 60 mg group: 0.7, p=0.785
R-107 30 mg group: 1.9, p=0.450
Rapid-acting antidepressant action in enrichment phase (open label 120 mg daily).
73% (168/231) TRD subject responded to enrichment treatment with a MADRS score of =12, and a reduction of >=50% on Day 8.
The MADRS changes from Day 1 to Day 8 are 31 to 13, with a difference 18 (n=231)
Incidence of TEAEs in randomization phase (% patient):
R-107 180 mg group: 94%
R-107 120 mg group: 81%
R-107 60 mg group: 77%
R-107 30 mg group: 65%
Placebo group: 70%