Date: 2015-10-26
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the annual meetings of ANESTHESIOLOGY® 2015 and The International Society of Anesthetic Pharmacologists in San Diego
Company: The Medicines Company (USA - NJ)
Product: ABP-700
Action
mechanism: allosteric modulator of the GABAA receptor. ABP-700 is a novel, positive allosteric modulator of the GABAA receptor currently being developed for general anesthesia and procedural sedation. ABP-700 is from a family of compounds invented by Dr. Douglas Raines at the Massachusetts General Hospital.
Disease: general anesthesia, procedural sedation
Therapeutic area: CNS diseases
Country:
Trial details:
Latest
news: * On October 26, 2015, The Medicines Company announced that results of the first-in-man study, ANVN-01, with ABP-700, a positive allosteric GABAA receptor modulator in development for general anesthesia and procedural sedation, were presented at the annual meetings of ANESTHESIOLOGY® 2015 and The International Society of Anesthetic Pharmacologists in San Diego. In addition to the pharmacokinetic and pharmacodynamic data presented at the meeting, data on the effects of ABP-700 on adrenal responsiveness from pre-clinical and two Phase I studies was also presented. ANVN-01 was a double-blind, randomized, placebo-controlled trial that evaluated the agent’s safety, tolerability, pharmacokinetics and pharmacodynamics in 60 healthy adult volunteers. ABP-700 was given as a single bolus intravenous injection of 0.03 to 1.0mg/kg. Pharmacokinetics were linear and dose-proportional. Depth and duration of sedation were dose dependent as measured by both Modified Observer’s Assessment of Alertness/Sedation scale (MOAA/S) and bispectral index (BIS) and rapidly reversing at all doses. There was no observed blood pressure reduction associated with ABP-700. Nausea or vomiting, common side effects from anesthesia, were reported in less than 2 percent of ABP-700 subjects. Adverse events related to involuntary muscle movement, tachycardia and respiratory effects were dose dependent and consistent with the mechanism of action of ABP-700. Also shown were data about ABP-700 effects on adrenal gland function. These data derive from two separate Phase I studies. In one study, subjects received placebo or a 0.03-1.0mg/kg bolus of APB-700; in the other, subjects received placebo or a 30-minute IV infusion of either ABP-700 (0.9 to 1.97 mg/kg) or propofol (2.25 mg/kg). Results showed that in adrenocortical responsiveness to synthetic ACTH stimulation one hour after bolus doses or 30-minute infusion doses was normal and indistinguishable from placebo or propofol. These results suggest that with ABP-700, any impact on adrenocortical steroid synthesis in humans after single bolus administration or short-term continuous infusion is likely to be brief, clinically unimportant, and equivalent to the current clinical standard of care, propofol.
