A Study to Assess the Effect of Ceftobiprole on the PK of Pitavastatin and on Plasma Levels of Coproporphyrin

Phase 1

Completed

• Conditions: Drug-drug Interaction Study
• Interventions: Drug: pitavastatin; Drug: pitavastatin single dose combined with ceftobiprole

• Registration Number: NCT06808646
• Lead Sponsor: Basilea Pharmaceutica

Brief Summary

The goal of this clinical study is 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 will be investigated by pharmacokinetic (PK) assessments.

The PK of pitavastatin will be assessed when administered alone and when administered together with ceftobiprole in a study design including two treatment periods.

The clinical study will also investigate the safety of ceftobiprole and how well ceftobiprole is tolerated by healthy subjects when it is administered in combination with pitavastatin. In addition, the effect of ceftobiprole on a specific marker, called coproporphyrin I, will be assessed in the blood.

The duration of the study will be a maximum of 38 days.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-09
• Study Start: 2025-01-17
• Study First Submitted QC: 2025-01-29
• Primary Completion: 2025-02-25
• Study Completion: 2025-02-25
• Status Verified: 2025-03
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Body mass index: 18.0 to 30.0 kg/m2, inclusive
• Good physical and mental health
• Normal renal function (creatinine clearance ≥ 90 mL/min as determined by the Cockcroft-Gault equation)
• Female participants of childbearing potential must not be pregnant or lactating and must must agree to use adequate contraception
• Male subjects, if not surgically sterilized, must agree to use adequate contraception
• All prescribed medication must have been stopped at least 30 days prior to admission to the clinical research center (an exception is made for hormonal contraceptives)
• All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (e.g., St. John's wort) must have been stopped at least 14 days prior to admission to the clinical research center
• Ability and willingness to abstain from alcohol from 48 hours (2 days) prior to Screening and admission to the clinical research center
• Ability and willingness to abstain from methylxanthine-containing beverages or food from 48 hours (2 days) prior to admission to the clinical research center

Main

Exclusion Criteria

• History of relevant drug and/or food allergies, particularly to antibiotics.
• Subject received a known potent inhibitor of OATP1B activity within 30 days prior to admission
• Subject received a potential inducer of OATP1B activity within 30 days prior to admission
• Subject has a history of seizures
• Subject has a history of frequent diarrhea
• Smoking more than 5 cigarettes, 1 cigar, or 1 pipe daily; the use of tobacco products in the 48 hours (2 days) prior to admission
• History of alcohol abuse or drug addiction within 12 months prior to Screening.
• Average intake of more than 24 units of alcohol per week
• Positive drug and/or alcohol screen
• Donation or loss of more than 450 mL of blood within 60 days prior to the first pitavastatin administration on Day 1 of the current study. Donation or loss of more than 1.5 liters of blood (for male subjects)/more than 1.0 liters of blood (for female subjects) in the 10 months prior to the first pitavastatin administration on Day 1 of the current study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Period 1; pitavastatin single dose, Period 2; pitavastatin single dose combined with ceftobiprole	pitavastatin	Period 1 On Day 1, a single oral dose of pitavastatin will be administered Period 2 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
Period 1; pitavastatin single dose, Period 2; pitavastatin single dose combined with ceftobiprole	pitavastatin single dose combined with ceftobiprole	Period 1 On Day 1, a single oral dose of pitavastatin will be administered Period 2 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

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) after a single oral dose of pitavastatin administered without and with intravenous (IV) ceftobiprole	Up to Day 8
Area under the plasma concentration-time curve up to time (AUC0-t) after a single oral dose of pitavastatin administered without and with IV ceftobiprole	Up to Day 8
Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) after a single oral dose of pitavastatin administered without and with IV ceftobiprole	Up to Day 8

Secondary Outcome Measures

Name	Time	Method
Cmax of coproporphyrin I (CP-I) after IV ceftobiprole administration	Up to Day 8
Area under the plasma level-time curve up to time 25.5 hours (AUEC0-25.5h) of CP-I after IV ceftobiprole administration	Up to Day 8
Cmax of IV ceftobiprole without and with oral administration of pitavastatin	Up to Day 8
Area under the plasma concentration-time curve up to 8 hours (AUC0-8h) after IV ceftobiprole without and with oral administration of pitavastatin	Up to Day 8
Cmax of the pitavastatin metabolite pitavastatin lactone after a single oral dose of pitavastatin, administered without and with IV ceftobiprole	Up to Day 8
AUC0-t of the pitavastatin metabolite pitavastatin lactone after a single oral dose of pitavastatin, administered without and with IV ceftobiprole	Up to Day 8
AUC0-inf of the pitavastatin metabolite pitavastatin lactone after a single oral dose of pitavastatin, administered without and with IV ceftobiprole	Up to Day 8
Number of participants reporting Treatment-emergent adverse events (TEAEs) after administration of ceftobiprole without and with a single oral dose of pitavastatin	Up to Day 17
Number of participants with clinically significant change from baseline in laboratory parameters after administration of ceftobiprole without and with a single oral dose of pitavastatin	Up to Day 17
Number of participants with clinically significant change from baseline in vital signs after administration of ceftobiprole without and with a single oral dose of pitavastatin	Up to Day 17
Number of participants with clinically significant change from baseline in 12-lead electrocardiogram (ECG) parameters after administration of ceftobiprole without and with a single oral dose of pitavastatin	Up to Day 17

Trial Locations

Locations (1)

ICON Early Clinical & Bioanalytical Solutions; 🇳🇱 Groningen, Netherlands