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

NCT06808646 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: BPR-CP-101HHSO100201600002C2024-518592-60-00
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug-drug Interaction Study

Keywords

Ceftobiprole; Pitavastatin; OATP1B; Coproporphyrin; DDI

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (8)

• Cmax of Coproporphyrin I (CP-I)

  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

  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

  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

  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

  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

Study Arms (2)

Period 1; pitavastatin 2 mg

EXPERIMENTAL

On Day 1, a single oral dose of pitavastatin was administered

Drug: pitavastatin

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.

Drug: pitavastatin single dose combined with ceftobiprole

Interventions

pitavastatin DRUG

Single oral administration

Period 1; pitavastatin 2 mg

pitavastatin single dose combined with ceftobiprole DRUG

Single oral pitavastatin co-administered with IV ceftobiprole

Period 2; pitavastatin 2 mg combined with ceftobiprole 500 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 were required not be pregnant or lactating and had to agree to use adequate contraception
• Male subjects, if not surgically sterilized, were required to agree to use adequate contraception
• All prescribed medication had to be stopped at least 30 days prior to admission to the clinical research center (an exception was made for hormonal contraceptives)
• All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (e.g., St. John's wort) had to be 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

You may not qualify if:

• 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 had a history of seizures
• Subject had 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.

Sponsors & Collaborators

• Basilea Pharmaceutica: lead
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (1)

ICON Early Clinical & Bioanalytical Solutions

Groningen, 9728, Netherlands

Location

MeSH Terms

Interventions

pitavastatin; ceftobiprole

Results Point of Contact

• Title: Thomas Kaindl, MD
• Organization: Basilea Pharmaceutica International Ltd, Allschwil

thomas.kaindl@basilea.com

+41615671505

Study Officials

• Thomas Kaindl, MD

  Basilea Pharmaceutica International Ltd, Allschwil

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: February 5, 2025
• Study Start: January 17, 2025
• Primary Completion: February 25, 2025
• Study Completion: February 25, 2025
• Last Updated: April 21, 2026
• Results First Posted: April 21, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)