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

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: Celecoxib; Drug: Rifampicin; Drug: Pyrazinamide

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Log change CFU.day (cumulative over 8 hours) calculated from Mycobacteria Growth Indicator Tube (MGIT) Time to Positivity	Cumulative whole blood bactericidal activity (WBA)	8 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of study drugs to determine the Area Under the Curve (AUC)	8 hours
Plasma concentrations of study drugs to determine the Maximum Plasma Concentration (Cmax)	8 hours

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: November 6, 2015
• First Submitted That Met QC Criteria: November 9, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cyclooxygenase 2 Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Celecoxib; Rifampin; Pyrazinamide
• Other Study ID Numbers: Celecoxib_WBA