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| ID | Type | Description | Link |
|---|---|---|---|
| C4791007 | Other Identifier | Alias Study Number |
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This is a Phase 1, open-label study to evaluate the drug-drug interaction potential of a strong CYP3A4 inhibitor (itraconazole) and a pan-CYP inducer (rifampin) on APX001 in two parallel groups of healthy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Drugs: APX001, itraconazole |
|
| Cohort 2 | Experimental | Drugs: APX001, rifampin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| APX001 | Drug | Cohort 1 Day 1: APX001 500 mg IV BID over a 3-hour infusion; Day 18: APX001 500 mg IV BID over a 3-hour infusion. Cohort 2 Day 1: APX001 1000 mg IV BID over a 3-hour infusion; Day 24: APX001 1000 mg IV BID over a 3-hour infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of APX001/APX001A as measured by area under the plasma concentration-time curve (AUC) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. | 6 weeks | |
| Pharmacokinetics of APX001/APX001A as measured by maximum observed plasma concentration (Cmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. | 6 weeks | |
| Pharmacokinetics of APX001/APX001A as measured by time to attain maximum observed plasma concentration (Tmax) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. | 6 weeks | |
| Pharmacokinetics of APX001/APX001A as measured by terminal elimination rate constant (λz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. | 6 weeks | |
| Pharmacokinetics of APX001/APX001A as measured by terminal elimination half-life (t1/2) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. | 6 weeks | |
| Pharmacokinetics of APX001/APX001A as measured by total clearance (CL) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. | 6 weeks | |
| Pharmacokinetics of APX001/APX001A as measured by the volume of distribution during the terminal phase (Vz) after multiple doses of a CYP3A4 inhibitor, itraconazole (oral solution) or multiple doses of a pan-CYP inducer, oral rifampin. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects experiencing and frequency of occurrence of adverse events as rated by CTCAE v5.0 after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. | 6 weeks | |
| Occurrence and magnitude of clinical lab test values outside the normal range, clinically significant, and differing from baseline results after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. |
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Inclusion Criteria:
Exclusion Criteria:
Additional Exclusion Criteria for Cohort 2:
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| Name | Affiliation | Role |
|---|---|---|
| Marc Engelhardt | Basilea Pharmaceutica International Ltd, Allschwil | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRA Health Sciences (PRA) - Early Development Services (EDS) | Groningen | 9728 NZ | Netherlands | |||
| PRA-EDS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38757982 | Derived | Hodges MR, van Marle S, Kramer WG, Ople E, Tawadrous M, Jakate A. Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants. Antimicrob Agents Chemother. 2024 Jun 5;68(6):e0165023. doi: 10.1128/aac.01650-23. Epub 2024 May 17. |
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| ID | Term |
|---|---|
| D009181 | Mycoses |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Itraconazole | Drug | Cohort 1 Days 15-30: itraconazole 200 mg oral solution QD. |
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| Rifampin | Drug | Cohort 2 Days 15-33: rifampin 600 mg oral QD. |
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| 6 weeks |
The following parameters will be measured:
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| 6 weeks |
| Occurrence of abnormal vital signs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. | Systolic and diastolic blood pressure and pulse will be recorded after the subject has been resting supine or semi-recumbent for at least 5 minutes. Body temperature and respiratory rate will be measured subsequently. | 6 weeks |
| Occurrence of abnormal, clinically significant results from 12-lead ECGs after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. | The following ECG parameters will be recorded: heart rate, PR interval, QRS duration, QT interval, and QTc interval (Fridericia's). | 6 weeks |
| Occurrence of changes in physical examinations which differ from baseline after dosing with APX001 IV alone and when co-administered with itraconazole (oral solution) or oral rifampin. | Physical examination will include: general appearance; skin/subcutaneous tissue; head; ears, nose, throat; neck and thyroid; thorax; lungs; cardiovascular; lymph nodes; abdomen; musculoskeletal; and neurological. | 6 weeks |
| Groningen |
| Netherlands |
| D010879 |
| Piperazines |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |