Date: 2016-01-05
Type of information: Results
phase: 3
Announcement: results
Company: Acacia Pharma (UK)
Product: Baremsis™ - APD421 (amisulpride - intravenous formulation of a currently marketed dopamine D2 antagonist for the new use of prevention and treatment of nausea & vomiting)
Action
mechanism: dopamine D2 antagonist.
Disease: prevention of post-operative nausea & vomiting (PONV) in high-risk patients
Therapeutic area: Gastrointestinal diseases - Digestive diseases
Country: France, Germany, USA
Trial details:
Latest
news: * On January 5, 2016, Acacia Pharma, a supportive care company, announced positive results from a Phase 3 study investigating Baremsis™ (amisulpride injection, formerly APD421) in combination with standard antiemetics for the prevention of post-operative nausea & vomiting in high-risk patients. The Phase 3 combination trial compared the prophylactic use of Baremsis™ plus a standard antiemetic (for example ondansetron or dexamethasone) against placebo plus a standard antiemetic. The primary endpoint was complete response, defined as no vomiting or retching and no requirement for antiemetic rescue medication in the first 24 hours after surgery. The study was one of the largest PONV studies ever undertaken and was conducted at multiple sites in Europe and the US. It recruited a total of 1,204 surgical patients with 3 or 4 risk factors for PONV (the “Apfel risk factors”), of whom 1,147 were evaluable. * On April 21, 2015, Acacia Pharma announced the initiation of a Phase 3 study investigating APD421 in combination with standard antiemetics, in the prevention of post-operative nausea & vomiting (PONV) in high-risk patients. The study is taking place in approximately 30 leading institutions in the USA, France, and Germany and aims to recruit up to 1,200 surgical patients at high-risk of suffering PONV over the next 6-12 months. The trial compares APD421 plus a standard anti-emetic (for example ondansetron or dexamethasone), against placebo plus the same standard anti-emetic. The primary endpoint is no vomiting or retching and no requirement for anti-emetic rescue medication in the first 24 hours after surgery. The incidence and severity of nausea are also being studied. Further studies are planned to investigate the use of APD421 in the treatment of established PONV, with the aim of seeking FDA regulatory approval and bringing the product onto the US market. Data generated by Acacia Pharma in Phase 2 and Phase 3 clinical trials indicate that APD421, its proprietary low dose intravenous formulation of the marketed dopamine antagonist amisulpride, is an effective, safe anti-emetic. The Company believes that a drug with these characteristics can be used to manage PONV: prophylactically in combination with standard antiemetics (eg 5HT3 antagonists and/or corticosteroids) in high-risk patients, and to rescue patients with PONV despite prior prophylaxis with non-dopamine-antagonist antiemetics. Amisulpride is also being developed by Acacia Pharma as APD403 for the prevention of chemotherapy induced nausea & vomiting (CINV).
Baremsis™ significantly improved the complete response rate when added on top of a standard antiemetic compared to placebo and a standard antiemetic (57.7% vs 46.6%, p=0.0002). In addition, all secondary efficacy endpoints, including the rate of vomiting, nausea and use of rescue medication, were also met. The safety profile of Baremsis™ was excellent. No toxicities of note were seen and the profile of adverse events and laboratory abnormalities was as good as placebo. Detailed data will be presented in due course at relevant scientific meetings and submitted for publication in a peer-reviewed journal.
International consensus guidelines recommend the use of combinations of antiemetics from different mechanistic classes for the prevention of PONV in high-risk patients acknowledging the multiple biological pathways that are implicated in PONV. Currently two classes of antiemetics are predominantly used to prevent PONV in these patients, 5HT3 antagonists (usually ondansetron) and corticosteroids (usually dexamethasone). However, a safe and effective third mechanism antiemetic is required and Baremsis™, as a dopamine antagonist, could fulfil this need.
