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| Name | Class |
|---|---|
| Biomedical Advanced Research and Development Authority | FED |
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This is a Phase 1, open-label, three-part, study in approximately 96 healthy adult participants between 18 and 55 years of age (both inclusive) (16 participants in Part 1, 20 participants in Part 2 and , and approximately 60 participants in Part 3). 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 , 43 days for Part 2 and 83 days for Part 3. All participants in Parts I und 2 will be screened within 28 days prior to dosing. All participants in Part 3 will be screened within 33 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. Participants in Part 3 will also return to the clinic for follow-up assessments 28 days ± 2 days and 42 days ± 2 days after the last dose of study intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 | Experimental | 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 (FDC) capsules; (c) Ceftibuten-ledaborbactam etzadroxil as FDC capsules after 5 days of esomeprazole orally once daily |
|
| Part 2 Group 1 | Experimental | Part 2 Group 1 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil FDC capsules for 7 days (Fasted Group) |
|
| Part 2 Group 2 | Experimental | Part 2 Group 2 will enroll 10 participants. Each will receive oral doses of Ceftibuten-ledaborbactam etzadroxil FDC capsules for 7 days (Fed Group) |
|
| Part 3 (Groups 1, 2, 4, 5, 6) | Experimental | Part 3 will enroll up to 50 participants. Each will receive oral doses of ceftibuten and/or ledaborbactam etzadroxil capsules (combined as FDC when administered together) in fed conditions |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ledaborbactam etzadroxil | Drug | capsules |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 Plasma PK AUC0-∞ (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil) | Area under the concentration time curve from time zero to infinity (AUC0-∞) | 0 - 48 hours on days 1, 4 and 11 |
| Part 1 Plasma PK Cmax (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil) | Maximum observed concentration (Cmax) | 0 - 48 hours on days 1, 4 and 11 |
| Proportion of participants of Part 2 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation. | Participants experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation. | Day 1 thru Day 18 (+/-1) |
| Proportion of participants of Part 3 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation. | Participants experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation. | Day 1 thru Day 49 (± 2 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants of Part 1 experiencing Treatment-emergent adverse events (TEAEs), Serious TEAEs, or TEAEs leading to discontinuation. | Participants 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Karine Litherland, PhD | Contact | +41616061111 | Karine.Litherland@basilea.com |
| Name | Affiliation | Role |
|---|---|---|
| Kamal Hamed, MD | Basilea Pharmaceutica International Ltd, Allschwil | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ICON, Clinical Research Phase I Unit | Recruiting | Lenexa | Kansas | 66219 | United States |
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| Part 3 Group 3 | Active Comparator | Part 3 Group 3 will enroll up to 10 participants. Each will receive oral doses of amoxicillin-clavulanate |
|
| Ceftibuten |
| Drug |
capsules |
|
| Ceftibuten-ledaborbactam etzadroxil | Drug | Fixed Dose Combination (FDC) |
|
| Esomeprazole | Drug | 40 mg capsule |
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| amoxicillin-clavulanate | Drug | 500 mg-125 mg oral doses |
|
Area under the concentration time curve from time zero to 12h (AUC0-12h) |
| Day 1 and Day 7 |
| Part 2 Plasma PK Cmax (ceftibuten, ledaborbactam, and ledaborbactam etzadroxil) | Maximum observed concentration (Cmax) | Day 1 and Day 7 |
| Part 3 Plasma PK AUC0-Tau (ceftibuten and/or ledaborbactam) | Area under the concentration time curve from time zero to Tau (AUC0-Tau) | At Day 1 and Day 7 |
| Part 3 Plasma PK Cmax (ceftibuten and/or ledaborbactam) | Maximum observed concentration (Cmax) | At Day 1 and Day 7 |
| ID | Term |
|---|---|
| D000077722 | Ceftibuten |
| D064098 | Esomeprazole |
| D019980 | Amoxicillin-Potassium Clavulanate Combination |
| ID | Term |
|---|---|
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009853 | Omeprazole |
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D001562 | Benzimidazoles |
| D019818 | Clavulanic Acid |
| D002969 | Clavulanic Acids |
| D000658 | Amoxicillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
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