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

NCT02602509 | Completed Phase 1

• 1 other identifier: Celecoxib_WBA
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

Celecoxib plus rifampicin group

EXPERIMENTAL

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

Drug: Celecoxib; Drug: Rifampicin

Celecoxib plus pyrazinamide group

EXPERIMENTAL

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

Drug: Celecoxib; Drug: Pyrazinamide

Interventions

Celecoxib DRUG

Also known as: Celebrex

Celecoxib plus pyrazinamide group; Celecoxib plus rifampicin group

Rifampicin DRUG

Also known as: Rifampin

Celecoxib plus rifampicin group

Pyrazinamide DRUG

Celecoxib plus pyrazinamide group

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

Celecoxib; Rifampin; Pyrazinamide

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Pyrazines

Study Officials

• Nicholas Paton

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2015
• First Posted: November 11, 2015
• Study Start: November 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: April 13, 2017

Record last verified: 2015-11

Locations

SG (1)