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| ID | Type | Description | Link |
|---|---|---|---|
| HHSO100201600002C | Other Grant/Funding Number | BARDA | |
| 2024-518592-60-00 | EU Trial (CTIS) Number |
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| Name | Class |
|---|---|
| Biomedical Advanced Research and Development Authority | FED |
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The goal of this clinical study was to determine the effect of the test drug ceftobiprole (a drug approved for the treatment of bacterial infections) on the elimination of pitavastatin (a drug approved for the treatment of increased levels of cholesterol in blood) from the body. This interaction was investigated by pharmacokinetic (PK) assessments. The clinical study also investigated the safety of ceftobiprole and how well ceftobiprole was tolerated by healthy subjects when it was administered in combination with pitavastatin.
This study assessed whether there was an inhibitory effect of ceftobiprole on hepatic organic anion-transporting polypeptide 1B (OATP1B) activity. Pitavastatin was used as an OATP1B substrate in this study. The pharmacokinetics of oral pitavastatin were assessed when administered alone and when administered together with IV ceftobiprole in a study design including 2 treatment periods. In addition, the pharmacodynamic effect of repeated doses of IV ceftobiprole on the diurnal plasma levels of coproporphyrin I (CP-I) was assessed in this study as CP-I is an endogenous biomarker for hepatic OATPB1 activity.
The study duration was up to 38 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Period 1; pitavastatin 2 mg | Experimental | On Day 1, a single oral dose of pitavastatin was administered |
|
| Period 2; pitavastatin 2 mg combined with ceftobiprole 500 mg | Experimental | From Day 4 to Day 7, ceftobiprole (as the prodrug ceftobiprole medocaril sodium) will be administered intravenously (IV) every 8 hours (q8h) for four days. On Day 6, a single oral dose of pitavastatin will be co-administered with ceftobiprole From Day 4 to Day 7, 500 mg ceftobiprole (as the prodrug ceftobiprole medocaril sodium) was administered as a 2-hour IV dose every 8 hours (q8h) under fasted conditions in the morning, and irrespective of timing of food intake further on the day. On Day 6, a single oral dose of 2 mg pitavastatin was co-administered with ceftobiprole 30 minutes prior to the end of the first IV dose of 500 mg ceftobiprole under fasted conditions. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pitavastatin | Drug | Single oral administration |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Pitavastatin | To assess the pharmacokinetic parameter Cmax in plasma after a single oral dose of pitavastatin administered without and with intravenous (IV) ceftobiprole | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
| Area Under the Plasma Concentration-time Curve up to Time (AUC0-t) After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-t after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
| Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-inf after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of Coproporphyrin I (CP-I) | The pharmacokinetic parameter Cmax for CP-I in plasma was assessed with and without administration of IV ceftobiprole | Sampling on Day 5; pre-dose, 2, 4, 6, 8 h, 16, and 25.5 (Day 6) hours post-dose and corresponding samples on Day -1 |
| Area Under the Plasma Level-time Curve up to Time 25.5 Hours (AUEC0-25.5h) of CP-I in Plasma |
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Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Kaindl, MD | Basilea Pharmaceutica International Ltd, Allschwil | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ICON Early Clinical & Bioanalytical Solutions | Groningen | 9728 | Netherlands |
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Twelve (12) subjects were enrolled in the study and completed the study as per protocol. The study was conducted in one research center in the Netherlands.
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| ID | Title | Description |
|---|---|---|
| FG000 | Entire Population of Subjects | Subjects received treatments in 2 periods: Period 1 (from Day -1 to Day 3): pitavastatin 2 mg single dose; and Period 2 (from Day 4 to Day 8): pitavastatin 2 mg single dose with ceftobiprole 500 mg as a 2-hour IV dose every 8 hours (q8h). On Day 6, a single oral dose of 2 mg pitavastatin was co-administered with ceftobiprole 30 minutes prior to the end of the first IV dose of 500 mg ceftobiprole |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Population of Subjects | Subjects received treatments in 2 periods: Period 1 (from Day -1 to Day 3): pitavastatin 2 mg single dose; and Period 2 (from Day 4 to Day 8): pitavastatin 2 mg single dose with ceftobiprole 500 mg as a 2-hour IV dose every 8 hours (q8h). On Day 6, a single oral dose of 2 mg pitavastatin was co-administered with ceftobiprole 30 minutes prior to the end of the first IV dose of 500 mg ceftobiprole |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Pitavastatin | To assess the pharmacokinetic parameter Cmax in plasma after a single oral dose of pitavastatin administered without and with intravenous (IV) ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng/mL | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
|
Up to 17 days after first dosing; Pitavastatin Period 1 between first dose on Day1 and before first dose on Day4; ceftobiprole Period 2 between first dose on Day4 and before first dose on Day6; pitavastatin + ceftopibrole Period 2 after first dose on Day6
A TEAE was defined as any event not present prior to the first administration of the study drug, or any event already present that worsens in either severity or frequency following exposure to the study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pitavastatin Period 1 | Subjects received (from Day -1 to Day 3) pitavastatin 2 mg single dose |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysgeusia | Nervous system disorders | MedDRA version 27.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Kaindl, MD | Basilea Pharmaceutica International Ltd, Allschwil | +41615671505 | thomas.kaindl@basilea.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 30, 2024 | Feb 25, 2026 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 24, 2025 | Feb 25, 2026 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 5, 2024 | Mar 26, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| C108475 | pitavastatin |
| C443755 | ceftobiprole |
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| pitavastatin single dose combined with ceftobiprole |
| Drug |
Single oral pitavastatin co-administered with IV ceftobiprole |
|
The pharmacokinetic parameter AUEC0-25.5h for CP-I was assessed with and without administration of IV ceftobiprole |
| Sampling on Day 5; pre-dose, 2, 4, 6, 8 h, 16, and 25.5 (Day 6) hours post-dose and corresponding samples on Day -1 |
| Cmax of Ceftobiprole in Plasma | To assess the pharmacokinetic parameter Cmax of IV ceftobiprole without and with oral administration of pitavastatin | Sampling on Day 5: pre-dose ,1, 2, 4, 6, 8 h post-dose, on Day 6; pre-dose,1, 2, 4, 6, 8 h post-dose |
| Area Under the Plasma Concentration-time Curve up to 8 Hours (AUC0-8h) After IV Ceftobiprole | To assess the pharmacokinetic parameter AUC0-8h after IV ceftobiprole without and with oral administration of pitavastatin | Sampling on Day 5: pre-dose ,1, 2, 4, 6, 8 h post-dose, on Day 6; pre-dose,1, 2, 4, 6, 8 h post-dose |
| Cmax of the Pitavastatin Metabolite Pitavastatin Lactone in Plasma After Pitavastatin Administration | To assess the pharmacokinetic parameter Cmax of pitavastatin lactone after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
| AUC0-t of the Pitavastatin Metabolite Pitavastatin Lactone in Plasma After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-t of pitavastatin lactone after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
| AUC0-inf of of the Pitavastatin Metabolite Pitavastatin Lactone in Plasma After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-inf of pitavastatin lactone after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftobiprole Without and With a Single Oral Dose of Pitavastatin | A treatment-emergent AE (TEAE) was defined as any event not present prior to the first administration of the study drug, or any event already present that worsens in either severity or frequency following exposure to the study drug | Up to 17 days after first dosing; Pitavastatin Period 1 between first dose on Day1 and before first dose on Day4; ceftobiprole Period 2 between first dose on Day4 and before first dose on Day6; pitavastatin + ceftopibrole Period 2 after first dose on Day6 |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Height (cm) | Mean | Standard Deviation | cm |
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| Weight (kg) | Mean | Standard Deviation | kg |
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| BMI | Mean | Standard Deviation | kg/m2 |
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| Period 2; Pitavastatin 2 mg Combined With Ceftobiprole 500 mg |
Subjects received (from Day 4 to Day 8) pitavastatin 2 mg single dose with ceftobiprole 500 mg as a 2-hour IV dose every 8 hours (q8h). On Day 6, a single oral dose of 2 mg pitavastatin was co-administered with ceftobiprole 30 minutes prior to the end of the first IV dose of 500 mg ceftobiprole |
|
|
| Primary | Area Under the Plasma Concentration-time Curve up to Time (AUC0-t) After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-t after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng x h/mL | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
|
|
|
| Primary | Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-inf after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng x h/mL | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
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|
|
| Secondary | Cmax of Coproporphyrin I (CP-I) | The pharmacokinetic parameter Cmax for CP-I in plasma was assessed with and without administration of IV ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng/mL | Sampling on Day 5; pre-dose, 2, 4, 6, 8 h, 16, and 25.5 (Day 6) hours post-dose and corresponding samples on Day -1 |
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|
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| Secondary | Area Under the Plasma Level-time Curve up to Time 25.5 Hours (AUEC0-25.5h) of CP-I in Plasma | The pharmacokinetic parameter AUEC0-25.5h for CP-I was assessed with and without administration of IV ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng x h/mL | Sampling on Day 5; pre-dose, 2, 4, 6, 8 h, 16, and 25.5 (Day 6) hours post-dose and corresponding samples on Day -1 |
|
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| Secondary | Cmax of Ceftobiprole in Plasma | To assess the pharmacokinetic parameter Cmax of IV ceftobiprole without and with oral administration of pitavastatin | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng/mL | Sampling on Day 5: pre-dose ,1, 2, 4, 6, 8 h post-dose, on Day 6; pre-dose,1, 2, 4, 6, 8 h post-dose |
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| Secondary | Area Under the Plasma Concentration-time Curve up to 8 Hours (AUC0-8h) After IV Ceftobiprole | To assess the pharmacokinetic parameter AUC0-8h after IV ceftobiprole without and with oral administration of pitavastatin | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng x h/mL | Sampling on Day 5: pre-dose ,1, 2, 4, 6, 8 h post-dose, on Day 6; pre-dose,1, 2, 4, 6, 8 h post-dose |
|
|
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| Secondary | Cmax of the Pitavastatin Metabolite Pitavastatin Lactone in Plasma After Pitavastatin Administration | To assess the pharmacokinetic parameter Cmax of pitavastatin lactone after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng/mL | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
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|
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| Secondary | AUC0-t of the Pitavastatin Metabolite Pitavastatin Lactone in Plasma After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-t of pitavastatin lactone after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng x h/mL | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
|
|
|
| Secondary | AUC0-inf of of the Pitavastatin Metabolite Pitavastatin Lactone in Plasma After Pitavastatin Administration | To assess the pharmacokinetic parameter AUC0-inf of pitavastatin lactone after a single oral dose of pitavastatin administered without and with IV ceftobiprole | Pharmacokinetic set: The PK set consisted of all subjects who received at least one dose of study drug and provided sufficient bioanalytical assessment results to calculate reliable estimates of the PK parameter | Posted | Geometric Mean | Full Range | ng x h/mL | Sampling on Day 1 and Day 6; before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 hours (h) post-dose. Day 2 and Day 7; 24 and 36 h post-dose. Day 3 and Day 8; 48 h post-dose |
|
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| Secondary | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) After Administration of Ceftobiprole Without and With a Single Oral Dose of Pitavastatin | A treatment-emergent AE (TEAE) was defined as any event not present prior to the first administration of the study drug, or any event already present that worsens in either severity or frequency following exposure to the study drug | safety set: The safety set consisted of all enrolled subjects who have received at least one dose of study drug | Posted | Count of Participants | Participants | Up to 17 days after first dosing; Pitavastatin Period 1 between first dose on Day1 and before first dose on Day4; ceftobiprole Period 2 between first dose on Day4 and before first dose on Day6; pitavastatin + ceftopibrole Period 2 after first dose on Day6 |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 5 |
| 12 |
| EG001 | Ceftobiprole Period 2 | Subjects received (from Day 4 to Day 8) pitavastatin 2 mg single dose with ceftobiprole 500 mg as a 2-hour IV dose every 8 hours (q8h) | 0 | 12 | 0 | 12 | 7 | 12 |
| EG002 | Pitavastatin + Ceftobiprole Period 2 | Subjects received (from Day 4 to Day 8) pitavastatin 2 mg single dose with ceftobiprole 500 mg as a 2-hour IV dose every 8 hours (q8h). On Day 6, a single oral dose of 2 mg pitavastatin was co-administered with ceftobiprole 30 minutes prior to the end of the first IV dose of 500 mg ceftobiprole | 0 | 12 | 0 | 12 | 5 | 12 |
| Headache | Nervous system disorders | MedDRA version 27.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA version 27.0 | Systematic Assessment |
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| Catheter site haematoma | General disorders | MedDRA version 27.0 | Systematic Assessment |
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| Catheter site irritation | General disorders | MedDRA version 27.0 | Systematic Assessment |
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| Feeling cold | General disorders | MedDRA version 27.0 | Systematic Assessment |
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| Feeling hot | General disorders | MedDRA version 27.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA version 27.0 | Systematic Assessment |
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| Vessel puncture site reaction | General disorders | MedDRA version 27.0 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA version 27.0 | Systematic Assessment |
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| Not any TEAE |
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