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1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study

BACKGROUND: In a previous phase 1b study, ≥ 90% of patients with cystitis treated with omadacycline (OMC), a novel intravenous (IV) and oral aminomethylcycline, achieved clinical success. We assessed the safety and efficacy of OMC vs nitrofurantoin (NIT) for treatment of cystitis in a randomized, ad...

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Autores principales: Overcash, J Scott, Tzanis, Evan, Manley, Amy, Sirbu, Alissa, Serio, Alisa W, White, Tiffany, Wright, Kelly, Chitra, Surya, Eckburg, Paul B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778228/
http://dx.doi.org/10.1093/ofid/ofaa439.1866
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author Overcash, J Scott
Tzanis, Evan
Manley, Amy
Sirbu, Alissa
Serio, Alisa W
White, Tiffany
Wright, Kelly
Chitra, Surya
Eckburg, Paul B
author_facet Overcash, J Scott
Tzanis, Evan
Manley, Amy
Sirbu, Alissa
Serio, Alisa W
White, Tiffany
Wright, Kelly
Chitra, Surya
Eckburg, Paul B
author_sort Overcash, J Scott
collection PubMed
description BACKGROUND: In a previous phase 1b study, ≥ 90% of patients with cystitis treated with omadacycline (OMC), a novel intravenous (IV) and oral aminomethylcycline, achieved clinical success. We assessed the safety and efficacy of OMC vs nitrofurantoin (NIT) for treatment of cystitis in a randomized, adaptive phase 2 study. METHODS: Females ≥18 years with uncomplicated symptomatic cystitis were randomized to oral dose regimens of OMC or NIT for 7 days (NCT03425396; Table 1). Efficacy was assessed for noninferiority by investigator’s assessment of clinical response (IACR) at post-treatment evaluation (PTE; primary endpoint; Day 14). Other endpoints included IACR, microbiologic response, and composite clinical and microbiologic response at end of treatment (EOT) and PTE. Treatment-emergent adverse events (TEAEs) were assessed. Results were reviewed by a data monitoring committee. Table 1 [Image: see text] RESULTS: Of 225 patients enrolled, 93.8% completed the study. Baseline (BL) characteristics were similar across groups, except Group 4, which was added late in the study based on blinded review of tolerability. (Table 2). Most patients had moderate BL symptoms of urinary tract infection. Among those with an identified pathogen, the most common species was E. coli. BL minimum inhibitory concentrations (MICs) against E. coli were 0.5 to 8 µg/mL for OMC and < 2 to 64 µg/mL for NIT. Clinical success rates for the intent-to-treat (ITT) population at PTE were high for all groups (OMC 78–88%; NIT 91%; Figure). Microbiologic response rates were higher with NIT vs OMC at PTE (Figure). Noninferiority of OMC to NIT was not met, as the lower limit of the 95% CI for treatment difference exceeded −10% (range −16.8% to −44.1%). OMC was generally well tolerated, with gastrointestinal disorders as the most frequent TEAEs (OMC 22%; NIT 14.8%). Table 2 [Image: see text] Figure [Image: see text] CONCLUSION: In this phase 2 study, clinical success rates were high in the OMC and NIT groups, although no OMC group met noninferiority criteria. Microbiological responses with all doses of OMC were generally lower than in the NIT group, potentially influenced by the higher BL MICs observed in this study compared with the previous phase 1b study. OMC was well tolerated, with a safety profile consistent with its current labeling. Further analyses are needed to fully understand study outcomes. DISCLOSURES: J. Scott Overcash, MD, FACEP, Paratek Pharmaceuticals, Inc. (Scientific Research Study Investigator) Evan Tzanis, BS, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Amy Manley, BS, Paratek Pharmaceuticals, Inc. (Employee) Alissa Sirbu, BSN, Paratek Pharmaceuticals, Inc. (Employee) Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Tiffany White, PhD, ContraFact Corporation (Consultant, (ended Feb 2020))Facile Therapeutics (Consultant)Paratek Pharmaceuticals, Inc. (Employee) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Surya Chitra, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Paul B. Eckburg, MD, AN2 Therapeutics (Consultant)Bugworks Research (Consultant)Curza (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant)SNIPR Biome (Consultant)Spero Therapeutics (Consultant)
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spelling pubmed-77782282021-01-07 1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study Overcash, J Scott Tzanis, Evan Manley, Amy Sirbu, Alissa Serio, Alisa W White, Tiffany Wright, Kelly Chitra, Surya Eckburg, Paul B Open Forum Infect Dis Poster Abstracts BACKGROUND: In a previous phase 1b study, ≥ 90% of patients with cystitis treated with omadacycline (OMC), a novel intravenous (IV) and oral aminomethylcycline, achieved clinical success. We assessed the safety and efficacy of OMC vs nitrofurantoin (NIT) for treatment of cystitis in a randomized, adaptive phase 2 study. METHODS: Females ≥18 years with uncomplicated symptomatic cystitis were randomized to oral dose regimens of OMC or NIT for 7 days (NCT03425396; Table 1). Efficacy was assessed for noninferiority by investigator’s assessment of clinical response (IACR) at post-treatment evaluation (PTE; primary endpoint; Day 14). Other endpoints included IACR, microbiologic response, and composite clinical and microbiologic response at end of treatment (EOT) and PTE. Treatment-emergent adverse events (TEAEs) were assessed. Results were reviewed by a data monitoring committee. Table 1 [Image: see text] RESULTS: Of 225 patients enrolled, 93.8% completed the study. Baseline (BL) characteristics were similar across groups, except Group 4, which was added late in the study based on blinded review of tolerability. (Table 2). Most patients had moderate BL symptoms of urinary tract infection. Among those with an identified pathogen, the most common species was E. coli. BL minimum inhibitory concentrations (MICs) against E. coli were 0.5 to 8 µg/mL for OMC and < 2 to 64 µg/mL for NIT. Clinical success rates for the intent-to-treat (ITT) population at PTE were high for all groups (OMC 78–88%; NIT 91%; Figure). Microbiologic response rates were higher with NIT vs OMC at PTE (Figure). Noninferiority of OMC to NIT was not met, as the lower limit of the 95% CI for treatment difference exceeded −10% (range −16.8% to −44.1%). OMC was generally well tolerated, with gastrointestinal disorders as the most frequent TEAEs (OMC 22%; NIT 14.8%). Table 2 [Image: see text] Figure [Image: see text] CONCLUSION: In this phase 2 study, clinical success rates were high in the OMC and NIT groups, although no OMC group met noninferiority criteria. Microbiological responses with all doses of OMC were generally lower than in the NIT group, potentially influenced by the higher BL MICs observed in this study compared with the previous phase 1b study. OMC was well tolerated, with a safety profile consistent with its current labeling. Further analyses are needed to fully understand study outcomes. DISCLOSURES: J. Scott Overcash, MD, FACEP, Paratek Pharmaceuticals, Inc. (Scientific Research Study Investigator) Evan Tzanis, BS, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Amy Manley, BS, Paratek Pharmaceuticals, Inc. (Employee) Alissa Sirbu, BSN, Paratek Pharmaceuticals, Inc. (Employee) Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Tiffany White, PhD, ContraFact Corporation (Consultant, (ended Feb 2020))Facile Therapeutics (Consultant)Paratek Pharmaceuticals, Inc. (Employee) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Surya Chitra, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Paul B. Eckburg, MD, AN2 Therapeutics (Consultant)Bugworks Research (Consultant)Curza (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant)SNIPR Biome (Consultant)Spero Therapeutics (Consultant) Oxford University Press 2020-12-31 /pmc/articles/PMC7778228/ http://dx.doi.org/10.1093/ofid/ofaa439.1866 Text en © The Author 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Poster Abstracts
Overcash, J Scott
Tzanis, Evan
Manley, Amy
Sirbu, Alissa
Serio, Alisa W
White, Tiffany
Wright, Kelly
Chitra, Surya
Eckburg, Paul B
1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study
title 1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study
title_full 1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study
title_fullStr 1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study
title_full_unstemmed 1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study
title_short 1688. Omadacycline in Female Adults With Cystitis: Results From a Randomized, Double-Blinded, Adaptive Phase 2 Study
title_sort 1688. omadacycline in female adults with cystitis: results from a randomized, double-blinded, adaptive phase 2 study
topic Poster Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778228/
http://dx.doi.org/10.1093/ofid/ofaa439.1866
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