Date: 2017-01-10
Type of information: Results
phase: 2
Announcement: results
Company: Debiopharm (Switzerland)
Product: Debio 1450
Action
mechanism: antibiotic. Debio 1450 is a prodrug of Debio 1452, a potent and selective FabI-inhibitor. FabI is a critical enzyme required for bacterial fatty acid biosynthesis. Debio 1452 has been successfully administered in a series of Phase I studies and a Phase 2 study where it demonstrated high efficacy in the treatment of acute bacterial skin and skin-structure infections (ABSSSI). Due to its unique selectivity for staphylococcal species, Debio 1450 is expected to preserve the human microbiota and thereby reduce antibiotic-associated side effects such as antibiotic-induced diarrhea or C. difficile overgrowth. Additionally, development of multiple drug-resistant organisms like VRE (vancomycin-resistant enterococci) is unlikely given the lack of activity on other bacterial species. Debio 1450 is efficiently and rapidly converted to the active metabolite Debio 1452 after both IV and oral administration in animals. Being able to treat staphylococcal infections with a safe treatment that allows for an IV/oral switch will bring much greater flexibility to physicians and patients and will be a major advance in addressing difficult-to-treat infections.
Disease: Acute Bacterial Skin and Skin Structure Infections (ABSSSI) due to Staphylococci
Therapeutic area: Infectious diseases
Country:
Trial
details: This Phase I, double-blind, placebo-controlled dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of single oral doses of Debio 1450 in healthy subjects. This study complements the IV single-ascending dose Phase I trial recently presented at the 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2014) in Barcelona. Part A, in particular, investigates the food and gastric pH effect of a single oral dose of Debio 1450 as well as the absolute bioavailability when compared to IV Debio 1450. Part B examines the dose proportionality of multiple ascending doses of Debio 1450 administered orally and IV.
Latest
news: * On January 10, 2017, Debiopharm announced positive results from a large Phase II study of the staphylococcal-selective antibiotic Debio 1450 for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI). This multi-center, randomized, double-blind study was designed to compare the efficacy, safety and tolerability of intravenous and oral Debio 1450 at two dose regimens with intravenous vancomycin / oral linezolid as an active comparator in 330 patients with clinically documented ABSSSI due to staphylococci including mostly Staphylococcus aureus sensitive or resistant to methicillin (MSSA or MRSA). The study objectives were met, demonstrating non-inferiority of Debio 1450 to comparator in all pathogenic staphylococci species infected patient populations including MRSA and ensuring that treatment with Debio 1450 at both doses was safe and well tolerated. The non-inferiority was also consistent across stratification parameters (Cellulitis and Diabetes Mellitus status). Study Primary Endpoint: Early Clinical Response and Rate (ECRR) at 48 to 72 hours in mITT population: Debio 1450 Debio 1450 Vancomycin 1g Overall 80mg/120mg BID 160mg/240 mg BID Linezolid 600mg BID ECCR (%) 94.6 90.1 91.1 91.9 * On April 23, 2015, Debiopharm International, part of Debiopharm Group™, a Swiss-based global biopharmaceutical company, announced the start of a clinical phase II study to evaluate Debio 1450 for the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) due to Staphylococci, including all resistant Staphylococcus strains, tested so far. This study is designed as a dose-response study to evaluate the efficacy of Debio 1450 in both intravenous (IV) and oral formulations versus intravenous vancomycin switched to oral linezolid in the treatment of ABSSSI. Safety and tolerability of both the IV and oral formulations of Debio 1450 will be evaluated by conventional endpoints. * On October 7, 2014, Debiopharm announced progress of its Phase I single and multiple ascending dose study of Debio 1450. This Phase I clinical trial in healthy subjects is a two part study to assess the safety, tolerability, and pharmacokinetics of Debio 1450. To date 20 subjects have been enrolled. This trial follows closely a single ascending dose study of Debio 1450 that is currently in its final stages. * On June 19, 2014, Debiopharm announced the launch of a Phase 1 dose-escalation study of Debio 1450 (previously known as AFN-1720), a highly potent anti-infective agent that is selectively active against a large number of Staphylococcus species, including all known resistant strains such as methicillin-resistant S. aureus (MRSA) and vancomycin-intermediate S. aureus (VISA).
The study was designed as a non-inferiority trial in accordance with the most recent Guidance issued by the FDA and was conducted at 25 sites in the United States of America. 330 patients were enrolled in the trial and randomized across three dosing arms.
Efficacy analyses were performed on the Microbiological Intent-to-Treat (mITT) population that includes all randomized patients who were culture positive for any staphylococcal species considered pathogenic and received at least one dose of the study drug.
Patients (n) 92 91 101 284
Responders (n) 87 82 92 261
Non Responders (n) 5 9 9 23
