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CompletedNCT02726438Updated Oct 18, 2017

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

A Phase 1 interventional study of Debio 1450 in Bone Diseases, Infectious, sponsored by Debiopharm International SA. Completed at 2 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2017-10-18.

Sponsored by Debiopharm International SA · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
17
Allocation
Non-randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Bone Diseases, Infectious
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
17 participants (actual)

Study arms

  • 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

  • No intervention
    Calibration

    A single participant will not receive the study drug, providing data to be used as calibration.

Interventions

  • DrugDebio 1450

    Debio 1450, 40 mg, powder for oral solution, for reconstitution in 5% dextrose in water.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 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 outcomes

  1. Plasma ratios for Debio 1452

    Categories: Bone marrow:plasma; soft tissue:plasma; synovial fluid:plasma

    Time frame: 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

  2. Area under the curve at steady state (AUCτ) of Debio 1452

    Time frame: 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

  3. Maximum observed plasma concentration (Cmax) of Debio 1452

    Time frame: 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

  4. Measured concentration at the end of a dosing interval at steady state (Ctrough) of Debio 1452

    Time frame: 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

06

Study locations

2 sites
  • eStudySite
    La Mesa, California 91941, United States
  • Mercury St Medical Group, PLLC
    Butte, Montana 59701, United States
07

References and documents

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. PubMed 30559136 ↗
08

Registry details

Key details

Study ID
NCT02726438
Lead sponsor
Debiopharm International SA
Responsible party
Sponsor
First posted
Apr 1, 2016
Start date
Apr 2016
Primary completion
Jun 2017
Completion
Jun 2017
Last update
Oct 18, 2017

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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