Douglas Pharmaceuticals announces positive top-line results from Phase 2 trial of R-107 in subjects with Treatment Resistant Depression

AUCKLAND, New Zealand, Dec. 16, 2021 /PRNewswire/ -- 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. This study was conducted in New Zealand, Australia, Singapore, and Taiwan from 2019 to 2021, with 231 TRD patients enriched, and 168 patients randomized.

TRD is defined as a lack of clinically meaningful improvement in depressed mood despite the use of adequate doses of at least two antidepressant agents, prescribed for adequate duration and with reasonable treatment adherence. There are currently limited treatment options available for patients with TRD.

Participants went through a one week open-label enrichment phase, where they received R-107 open-label 120 mg/day for 5 days. Those who had an improvement in depressed mood were randomized to receive double-blinded placebo, 30, 60, 120, or 180 mg R-107 doses twice a week for 84 days. The primary endpoint was a change in ratings on a standard depression rating scale, the Montgomery-Asberg Depression Rating Scale (MADRS).

During the enrichment phase, 73% (168/231) of TRD patients rapidly remitted (MADRS score ≤12) within one week from the open-label treatment of R-107 120 mg daily. Mean MADRS scores fell from 31 to 13 during the enrichment phase.

The primary efficacy analysis showed that the 180 mg dose group demonstrated a statistically significant mean reduction of 6.1 points in MADRS score at the end of the study compared with the placebo group (p=0.019). The 30 mg, 60 mg, and 120 mg groups showed MADRS score reductions of 1.9, 0.7, and 4.5 points respectively, compared to placebo, which were not statistically significant.

R-107 was generally well tolerated. The most common TEAEs across dose groups (>10% overall incidence) were headache, dizziness, and anxiety. There were no product-related Serious Adverse Events (SAE) reported in the study.

Douglas intends to start Phase 3 study in 2022 with the optimal dosing protocol confirmed by this Phase 2 study.

Dr Peter Surman, Chief Scientific Officer of Douglas commented, "We saw a clear dose-response pattern from the efficacy data, that makes us confident to choose an optimal dosing protocol for the Phase 3 study. With the compelling data from the BEDROC trial, both in the rapidity and durability of response, we are looking forward to moving the development of R-107 into pivotal trials. We would like to thank the participating investigators for their commitment to the study, especially in coping with the changes brought about from the Covid-19 pandemic. We look forward to continuing the development of R-107 with the goal of bringing a new effective treatment to the millions of patients suffering with TRD."

Jeff Douglas, Managing Director of Douglas went on to say that "Clinically meaningful efficacy as an anti-depressant could make R-107 an ideal therapy for people who suffer with TRD, often for years, without relief. The rapid on-set of remission within one week is particularly appealing compared to current treatments where patients can take four to six weeks to see a significant improvement in mood."

"As a researcher, and as a psychiatrist and clinician who treats many patients with TRD, I am really encouraged by these data," said Professor Paul Glue, MD, University of Otago, Hazel Buckland Professor, Chair of the Trial Steering Committee for BEDROC. "The rapid onset of treatment response with R-107, and the excellent tolerability compared with other ways of dosing ketamine, is particularly impressive. If confirmed in pivotal trials, R-107 could have a significant impact on how we treat patients with TRD."

About R-107
Douglas is developing R-107 as a rapidly acting oral agent for the treatment of depression. Ketamine works as a NMDA receptor antagonist. R-107 is formulated to release the ketamine at a slow and steady rate over 12 hours to minimise psychotomimetic side-effects associated with other ketamine dosage forms.

Phase 2 BEDROC study key findings

• Mean total MADRS changes from Day 1 to 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 effect in enrichment phase (open-label 120 mg daily):
• 73% (168/231) TRD subjects responded to the enrichment treatment, with a MADRS score ≤12 and a reduction ≥50% at Day 8;
• The MADRS change from Day 1 to Day 8 is from 31 to 13 with a difference of 18 (n=231)
• TEAEs incidence in randomization phase (% of 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%

About Douglas
Douglas Pharmaceuticals is New Zealand's largest pharmaceutical company, employing over 700 people and exporting prescription products to over 30 countries around the world. Douglas is headquartered in Auckland and has sites in Fiji and Pennsylvania. Douglas works with innovative partners to research, develop, manufacture, and commercialise drug repurposing assets to address serious unmet medical needs.

Contact Information
Daina Cardillo Basile
Kovak-Likly Communications
Email: [email protected]

SOURCE Douglas Pharmaceuticals Ltd