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Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers

Sponsor
National University Hospital, Singapore (Other)
Overall Status
Completed
CT.gov ID
NCT02602509
Collaborator
(none)
18
Enrollment
1
Location
2
Arms
3
Duration (Months)
6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the bactericidal activity against Mycobacterium tuberculosis of celecoxib in combination with established drugs used to treat tuberculosis (TB). Pharmacokinetics (PK) and whole blood bactericidal activity (WBA) will be measured in healthy volunteers following administration of the study drugs alone and in combination.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The whole blood bactericidal activity (WBA) assay is an ex vivo model for measuring the combined effects of administered drugs, host factors and strain factors on mycobacterial sterilisation. If performed in parallel with PK measurements, the method can be used to evaluate the effect of drugs throughout the dosing cycle. Celecoxib is a COX-2 inhibitor with immuno-modulatory properties important in the host defence against tuberculosis (TB). The aim of this trial is to investigate the effect on WBA of manipulation of the host response to TB using celecoxib, in combination with established TB drugs.

Study Design

Study Type:
Interventional
Actual Enrollment :
18 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers
Study Start Date :
Nov 1, 2015
Actual Primary Completion Date :
Feb 1, 2016
Actual Study Completion Date :
Feb 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Celecoxib plus rifampicin group

Visit 1: Celecoxib 400mg Visit 2: Rifampicin 10mg/kg Visit 3: Celecoxib 400mg PLUS rifampicin 10mg/kg

Drug: Celecoxib
Other Names:
  • Celebrex

    • Drug: Rifampicin
    Other Names:
  • Rifampin

    		•
    Experimental: Celecoxib plus pyrazinamide group

    Visit 1: Celecoxib 400mg Visit 2: Pyrazinamide 25mg/kg Visit 3: Celecoxib 400mg PLUS pyrazinamide 25mg/kg

    Drug: Celecoxib
    Other Names:
  • Celebrex

    • Drug: Pyrazinamide

    Outcome Measures

    Primary Outcome Measures

    1. Log change CFU.day (cumulative over 8 hours) calculated from Mycobacteria Growth Indicator Tube (MGIT) Time to Positivity [8 hours]

      Cumulative whole blood bactericidal activity (WBA)

    Secondary Outcome Measures

    1. Plasma concentrations of study drugs to determine the Area Under the Curve (AUC) [8 hours]

    2. Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax) [8 hours]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    1. Aged over 21 years and below 60 years old

    2. Male or female willing to comply with the study visits and procedures

    3. Willing and able to provide written informed consent

    Exclusion Criteria:

    1. Women who are currently pregnant or breastfeeding

    2. Body weight below 50kg

    3. Clinical signs of active TB in the opinion of the investigator

    4. Previous hypersensitivity, intolerance or allergy to rifampicin, pyrazinamide, COX-2 inhibitors, non-steroidal anti-inflammatory drugs or sulfonamides

    5. Current use of any drugs or medication known to have an interaction with rifampicin, pyrazinamide or celecoxib

    6. Current use or use in the last 2 weeks of non-steroidal anti-inflammatory drugs or COX-2 inhibitors

    7. Current use or use in the last 2 weeks of any drugs, over the counter or herbal preparations that are known or potential inhibitors or inducers of cytochrome P450 enzymes

    8. Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations

    9. Known hepatic disease, recent hepatitis (within last 6 months) or alcohol abuse

    10. Known cardiovascular disease, heart failure, stroke or current cardiovascular risk factors

    11. Known peptic ulcer disease, previous gastrointestinal bleed or current risk factors for gastrointestinal events

    12. Acute or previous gout, acute porphyria

    13. Any other significant condition that would, in the opinion of the investigator, compromise the volunteer's safety or outcome in the trial

    14. Current participation in other clinical intervention trial or research protocol

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National University Hospital Singapore Singapore

    Sponsors and Collaborators

    • National University Hospital, Singapore

    Investigators

    • Principal Investigator: Nicholas Paton, National University Hospital, Singapore

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National University Hospital, Singapore
    ClinicalTrials.gov Identifier:
    NCT02602509
    Other Study ID Numbers:
    • Celecoxib_WBA
    First Posted:
    Nov 11, 2015
    Last Update Posted:
    Apr 13, 2017
    Last Verified:
    Nov 1, 2015
    Additional relevant MeSH terms:
    Tuberculosis
    Rifampin
    Pyrazinamide
    Celecoxib

    Study Results

    No Results Posted as of Apr 13, 2017