A Phase 1, Open-label Study to Evaluate the Safety and to Characterize the Pharmacokinetics of a Fixed-Dose Combination Formulation of Ceftibuten-Ledaborbactam Etzadroxil
Overview
- Phase
- Phase 1
- Intervention
- Ledaborbactam etzadroxil
- Conditions
- Healthy Volunteer
- Sponsor
- Basilea Pharmaceutica
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Part 1 Plasma PK AUC0-∞ (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a Phase 1, open-label, two-part, study in approximately 46 healthy adult participants between 18 and 55 years of age (both inclusive) (at least 16 participants in Part 1 and up to 30 participants in Part 2). The study will be conducted at one clinical site in the United States. Participants in Part 1 and Part 2 may be conducted in parallel. The duration of an individual participation will be approximately 46 days for Part 1 and 43 days for Part 2. All participants will be screened within 28 days prior to dosing. They will be admitted to the clinical research unit (CRU) the day prior to dosing and will remain in the CRU until the end of the PK sample collection period. All participants will return to the clinic for follow-up assessments 7 days ± 1 day after the last dose of study intervention.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adult male or female, between 18 and 55 years of age
- •Body mass index ≥ 18 and ≤ 32 kg/m2
- •Laboratory values meeting defined laboratory ranges
- •Males or non-pregnant, non-lactating females
Exclusion Criteria
- •History of any hypersensitivity reaction following administration of a cephalosporin, penicillin, or other β-lactam antibacterial drug
- •Any acute illness or surgery within the past 3 months determined by the investigator to be clinically relevant
- •Positive alcohol, drug or tobacco use/test
Arms & Interventions
Part 1
Part 1 will enroll at least 16 participants who will receive a single oral dose of ceftibuten and ledaborbactam etzadroxil following a 10-hour fast on 3 occasions in a fixed sequence: (a) Ceftibuten and ledaborbactam etzadroxil as separate capsules; (b) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules; (c) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules after 5 days of esomeprazole orally once daily
Intervention: Ledaborbactam etzadroxil
Part 1
Part 1 will enroll at least 16 participants who will receive a single oral dose of ceftibuten and ledaborbactam etzadroxil following a 10-hour fast on 3 occasions in a fixed sequence: (a) Ceftibuten and ledaborbactam etzadroxil as separate capsules; (b) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules; (c) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules after 5 days of esomeprazole orally once daily
Intervention: Ceftibuten
Part 1
Part 1 will enroll at least 16 participants who will receive a single oral dose of ceftibuten and ledaborbactam etzadroxil following a 10-hour fast on 3 occasions in a fixed sequence: (a) Ceftibuten and ledaborbactam etzadroxil as separate capsules; (b) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules; (c) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules after 5 days of esomeprazole orally once daily
Intervention: Ceftibuten-ledaborbactam etzadroxil
Part 1
Part 1 will enroll at least 16 participants who will receive a single oral dose of ceftibuten and ledaborbactam etzadroxil following a 10-hour fast on 3 occasions in a fixed sequence: (a) Ceftibuten and ledaborbactam etzadroxil as separate capsules; (b) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules; (c) Ceftibuten-ledaborbactam etzadroxil as fixed-dose combination capsules after 5 days of esomeprazole orally once daily
Intervention: Esomeprazole
Part 2 Group 1
Part 2 Group 1 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil as fixed-dose capsules for 7 days (Fasted Group)
Intervention: Ceftibuten-ledaborbactam etzadroxil
Part 2 Group 2
Part 2 Group 2 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil as fixed-dose capsules for 7 days (Fed Group)
Intervention: Ceftibuten-ledaborbactam etzadroxil
Part 2 Group 3
Part 2 Group 3 will possibly enroll 10 participants. Following availability of PK and safety data from Groups 1 and 2, a determination will be made regarding whether or not Group 3 is needed and the dosing conditions that apply
Intervention: Ceftibuten-ledaborbactam etzadroxil
Outcomes
Primary Outcomes
Part 1 Plasma PK AUC0-∞ (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)
Time Frame: 0 - 48 hours on days 1, 4 and 11
Area under the concentration time curve from time zero to infinity (AUC0-∞)
Part 1 Plasma PK Cmax (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)
Time Frame: 0 - 48 hours on days 1, 4 and 11
Maximum observed concentration (Cmax)
Proportion of participants of Part 2 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.
Time Frame: Day 1 thru Day 18 (+/-1)
Participants experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.
Secondary Outcomes
- Proportion of participants of Part 1 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation.(Day 1 thru Day 18 (+/-1))
- Part 2 Plasma PK AUC0-12h (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)(Day 1 and Day 7)
- Part 2 Plasma PK Cmax (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil)(Day 1 and Day 7)