Drug Penetration Into Bone After Repeated Oral Administration of Debio 1450 to Patients Undergoing Hip Replacement Surgery

A Phase 1, Open-Label Pharmacokinetic Study to Investigate Drug Penetration in the Bone After Repeated Oral Administration of Debio 1450 to Patients Undergoing Hip Replacement Surgery

Debio 1450 is being developed for the treatment of staph (staphylococcal) infections. How fast and completely an antibiotic penetrates into bone is used to determine how effective it might be to treat infections related to bones or joints. Since bone has fewer blood vessels than other tissue (for example lung tissue or the skin), drugs have a harder time getting into them. It is important to find out how much of the antibiotic can get into the bone to help patients with bone infections.

Study Overview

• Status: Completed
• Conditions: Bone Diseases, Infectious
• Intervention / Treatment: Drug: Debio 1450

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91941
      • eStudySite
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury St Medical Group, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets protocol-specified criteria for qualification and contraception
• Is willing and able to comply with restrictions related to food, drink and medications
• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

Exclusion Criteria:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters

• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:

  1. the safety or well-being of the participant or study staff;
  2. the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);
  3. the analysis of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Debio 1450; Participants will receive 3 oral administrations of Debio 1450 at a dose of 240 mg approximately 12 hours apart. The last dose should be given approximately 2, 4, 6 or 12 hours prior to surgery with 3 patients each to be dosed at each of these time points. If the surgery is delayed by more than 12 hours postdose, the patients could receive up to 2 additional administrations (approximately 12 hours apart) to ensure that the last dose is administered between 2 and 12 hours before the surgery.	Drug: Debio 1450; Debio 1450, 40 mg, powder for oral solution, for reconstitution in 5% dextrose in water.
No Intervention: Calibration; A single participant will not receive the study drug, providing data to be used as calibration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone to plasma ratio for Debio 1452 (the Debio 1450 active moiety)	Bone/bone marrow/soft tissue/synovial fluid samples will be collected during surgery; time of resection will be used to calculate the elapsed time after last dosing.	at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma ratios for Debio 1452	Categories: Bone marrow:plasma; soft tissue:plasma; synovial fluid:plasma	at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant
Area under the curve at steady state (AUCτ) of Debio 1452		at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant
Maximum observed plasma concentration (Cmax) of Debio 1452		at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant
Measured concentration at the end of a dosing interval at steady state (Ctrough) of Debio 1452		at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant

Collaborators and Investigators

• Sponsor: Debiopharm International SA

Publications and helpful links

General Publications

• Menetrey A, Janin A, Pullman J, Overcash JS, Haouala A, Leylavergne F, Turbe L, Wittke F, Nicolas-Metral V. Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e01669-18. doi: 10.1128/AAC.01669-18. Print 2019 Mar.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (Estimate): April 1, 2016

Study Record Updates

• Last Update Posted (Actual): October 18, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Musculoskeletal Diseases; Infections; Communicable Diseases; Bone Diseases; Bone Diseases, Infectious
• Other Study ID Numbers: Debio 1450-108; 226488 (Other Identifier: CRO)