Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers
Primary Purpose
Tuberculosis
Status
Completed
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
Celecoxib
Rifampicin
Pyrazinamide
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis
Eligibility Criteria
Inclusion Criteria:
- Aged over 21 years and below 60 years old
- Male or female willing to comply with the study visits and procedures
- Willing and able to provide written informed consent
Exclusion Criteria:
- Women who are currently pregnant or breastfeeding
- Body weight below 50kg
- Clinical signs of active TB in the opinion of the investigator
- Previous hypersensitivity, intolerance or allergy to rifampicin, pyrazinamide, COX-2 inhibitors, non-steroidal anti-inflammatory drugs or sulfonamides
- Current use of any drugs or medication known to have an interaction with rifampicin, pyrazinamide or celecoxib
- Current use or use in the last 2 weeks of non-steroidal anti-inflammatory drugs or COX-2 inhibitors
- 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
- Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations
- Known hepatic disease, recent hepatitis (within last 6 months) or alcohol abuse
- Known cardiovascular disease, heart failure, stroke or current cardiovascular risk factors
- Known peptic ulcer disease, previous gastrointestinal bleed or current risk factors for gastrointestinal events
- Acute or previous gout, acute porphyria
- Any other significant condition that would, in the opinion of the investigator, compromise the volunteer's safety or outcome in the trial
- Current participation in other clinical intervention trial or research protocol
Sites / Locations
- National University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Celecoxib plus rifampicin group
Celecoxib plus pyrazinamide group
Arm Description
Visit 1: Celecoxib 400mg Visit 2: Rifampicin 10mg/kg Visit 3: Celecoxib 400mg PLUS rifampicin 10mg/kg
Visit 1: Celecoxib 400mg Visit 2: Pyrazinamide 25mg/kg Visit 3: Celecoxib 400mg PLUS pyrazinamide 25mg/kg
Outcomes
Primary Outcome Measures
Log change CFU.day (cumulative over 8 hours) calculated from Mycobacteria Growth Indicator Tube (MGIT) Time to Positivity
Cumulative whole blood bactericidal activity (WBA)
Secondary Outcome Measures
Plasma concentrations of study drugs to determine the Area Under the Curve (AUC)
Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax)
Full Information
NCT ID
NCT02602509
First Posted
November 6, 2015
Last Updated
April 12, 2017
Sponsor
National University Hospital, Singapore
1. Study Identification
Unique Protocol Identification Number
NCT02602509
Brief Title
Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers
Official Title
Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Celecoxib plus rifampicin group
Arm Type
Experimental
Arm Description
Visit 1: Celecoxib 400mg Visit 2: Rifampicin 10mg/kg Visit 3: Celecoxib 400mg PLUS rifampicin 10mg/kg
Arm Title
Celecoxib plus pyrazinamide group
Arm Type
Experimental
Arm Description
Visit 1: Celecoxib 400mg Visit 2: Pyrazinamide 25mg/kg Visit 3: Celecoxib 400mg PLUS pyrazinamide 25mg/kg
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebrex
Intervention Type
Drug
Intervention Name(s)
Rifampicin
Other Intervention Name(s)
Rifampin
Intervention Type
Drug
Intervention Name(s)
Pyrazinamide
Primary Outcome Measure Information:
Title
Log change CFU.day (cumulative over 8 hours) calculated from Mycobacteria Growth Indicator Tube (MGIT) Time to Positivity
Description
Cumulative whole blood bactericidal activity (WBA)
Time Frame
8 hours
Secondary Outcome Measure Information:
Title
Plasma concentrations of study drugs to determine the Area Under the Curve (AUC)
Time Frame
8 hours
Title
Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax)
Time Frame
8 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Aged over 21 years and below 60 years old
Male or female willing to comply with the study visits and procedures
Willing and able to provide written informed consent
Exclusion Criteria:
Women who are currently pregnant or breastfeeding
Body weight below 50kg
Clinical signs of active TB in the opinion of the investigator
Previous hypersensitivity, intolerance or allergy to rifampicin, pyrazinamide, COX-2 inhibitors, non-steroidal anti-inflammatory drugs or sulfonamides
Current use of any drugs or medication known to have an interaction with rifampicin, pyrazinamide or celecoxib
Current use or use in the last 2 weeks of non-steroidal anti-inflammatory drugs or COX-2 inhibitors
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
Evidence of renal or hepatic dysfunction or any clinically significant deviation from normal during screening including laboratory determinations
Known hepatic disease, recent hepatitis (within last 6 months) or alcohol abuse
Known cardiovascular disease, heart failure, stroke or current cardiovascular risk factors
Known peptic ulcer disease, previous gastrointestinal bleed or current risk factors for gastrointestinal events
Acute or previous gout, acute porphyria
Any other significant condition that would, in the opinion of the investigator, compromise the volunteer's safety or outcome in the trial
Current participation in other clinical intervention trial or research protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas Paton
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University Hospital
City
Singapore
Country
Singapore
12. IPD Sharing Statement
Learn more about this trial
Evaluating Celecoxib Activity in Mycobacterium Tuberculosis: A Whole Blood Bactericidal Activity Study in Healthy Volunteers
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