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

NCT ID: NCT02602509

Last Updated: 2017-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2016-02-29

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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Celecoxib plus rifampicin group

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

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

Rifampicin

Intervention Type: DRUG

Celecoxib plus pyrazinamide group

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

Group Type: EXPERIMENTAL

Celecoxib

Intervention Type: DRUG

Pyrazinamide

Intervention Type: DRUG

Interventions

Celecoxib

Intervention Type: DRUG

Rifampicin

Intervention Type: DRUG

Pyrazinamide

Intervention Type: DRUG

Other Intervention Names

Celebrex; Rifampin

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicholas Paton

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

National University Hospital

Singapore, , Singapore

Countries

Singapore

Other Identifiers

Celecoxib_WBA

Identifier Type: -

Identifier Source: org_study_id