Data from Pharmawand - Curated by Marshall Pearce - Date added 10 October 2017
Paratek Pharmaceuticals announced the results of three sub-analyses from the Phase III OASIS-1 study that show a consistent safety and efficacy profile of its once-daily oral and intravenous (IV), broad-spectrum investigational antibiotic, omadacycline, when treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in patients with comorbid conditions, which could be associated with reduced treatment efficacy./p>
The analyses compared omadacycline to linezolid in subsets of ABSSSI patients enrolled in the global Phase III registration study with: chronic kidney disease; high body mass index; diabetes, and a history of intravenous drug users with or without hepatitis C infection. In addition to omadacycline demonstrating a consistent efficacy and safety profile compared to linezolid, these data suggest that no dose adjustments for omadacycline are required in patients with these comorbid conditions.
OASIS-1 (Omadacycline in Acute Skin Structure Infections Study) evaluated the efficacy and safety of IV-to-oral once-daily omadacycline against twice-daily linezolid over a 7 to 14-day course of therapy in 645 treated patients. The primary efficacy endpoint for the FDA was early clinical response (ECR) at 48 to 72 hours after the first dose of study drug in the modified intent-to-treat (mITT) population (patients without a potentially causative monomicrobial gram-negative infection). In the mITT analysis population, omadacycline achieved the primary efficacy endpoint of statistical non-inferiority (10% margin) compared to linezolid. The ECR for the omadacycline and linezolid treatment arms was 84.8% compared to 85.5%, respectively.
Omadacycline in Chronic Kidney Disease with ABSSSI: In this safety analysis, 522 patients had stage 0/1 chronic kidney disease (CKD-0/1), 119 had stage 2/3 chronic kidney disease (CKD-2/3). Response rates at ECR assessment were slightly higher in patients with CKD-0/1 in the omadacycline group (87.4%) compared to patients with CKD-2/3 (82.3%). Similarly, for patients treated with linezolid, ECR rates were 87.1% and 83.7% for CKD-0/1 and CKD-2/3, respectively. PTE responses in the mITT population were 87.0% for omadacycline vs. 84.8% for linezolid in CKD-0/1 patients. In patients with CKD-2/3, rates were 90.3% vs. 85.7% for omadacycline and linezolid, respectively. PTE responses in the CE population were 96.7% for omadacycline vs. 94.4% for linezolid in CKD-0/1 patients, and 94.7% for omadacycline vs. 91.1% for linezolid in patients with CKD-2/3. Overall, omadacycline was safe and generally well tolerated in patients with CKD, with similar AEs to subjects without CKD. Overall, the safety and efficacy of omadacycline in patients with CKD-0/1 and CKD-2/3 was similar to that observed in the general population. TEAEs were comparable between omadacycline and linezolid treatment.
Omadacycline in Diabetic and Obese Patients with ABSSSI: In the sub-analyses comparing omadacycline to linezolid in patients with high BMI, evaluable patients had elevated BMI of ?25 (n=417). Of those, 225 were overweight (25 < BMI <30) and 192 were obese (BMI > 30); irrespective of BMI, 59 patients had a medical history of diabetes. Omadacycline outcomes were comparable at ECR assessments in patients with normal (BMI <25) and high BMI. Outcomes in the high-BMI omadacycline treatment group were comparable to outcomes in the linezolid treatment group for the primary endpoint in the mITT (84.8% vs. 85.9%). At PTE, high BMI omadacycline-treated patients showed higher clinical success than linezolid-treated patients (85.9% vs. 83.4%) in the mITT population. PTE response in the high BMI CE population were 95.8% for omadacycline vs. 93.1% for linezolid. At PTE, in both the mITT and CE populations, omadacycline-treated diabetic patients showed higher clinical success compared to linezolid-treated diabetic patients. Overall, the safety and efficacy of omadacycline was consistent regardless of BMI or diabetes diagnosis.
Omadacycline in ABSSSI Patients with a History of IV Drug Use (IVDU) and Hepatitis C (HCV+): In this analysis, 322 patients were IVDU and 168 were IVDU/HCV+. ECR rates were comparable for both omadacycline and linezolid in both IVDU and non-IVDU patients, regardless of HCV diagnosis. PTE responses with omadacycline were higher than linezolid in non-IVDU patients in both the mITT and clinically evaluable (CE) populations. For both omadacycline and linezolid, clinical success at PTE tended to be lower among IVDU and IVDU/HCV+ patients, compared with the non-IVDU and non-IVDU/HCV- patients in the mITT populations. The lower clinical success observed among IVDU and IVDU/HCV+ patients was due to the greater number of indeterminate responses (e.g. lost to follow-up, withdrew consent). Tolerability was similar across all patient groups, with no major differences in liver function.25>30>