The Safety of Tuberculosis Treatments by Oral Inhalation
Clinical Trial Phase I of Antituberculosis Dry Powder Aerosols
1 other identifier
interventional
40
1 country
1
Brief Summary
The inhaled route of delivery has always been associated with the considerable challenge of getting the drug to its target. The lungs are a highly complex organ designed to filter inspired air, with many different cell types contributing to their function. Furthermore, the lungs may change dramatically when afflicted by disease resulting in an internal environment that works against the drug reaching and interacting successfully with the target. For targets in the upper airways this will have lesser significance, but drug delivery to the deep lung may be impeded by changes such as mucus hyper-secretion or thickening or airway narrowing. In order to interpret toxicology findings it is necessary to reconcile test sensitivity, background biological variation, normal responses to inhaled materials and drug or medicine-specific adverse effects. Identification of adverse end-points is an area where better control data sets might help discern true adverse effects from a normal physiological lung response. The lung responds acutely to inhalation of irritant materials by hyper-secretion of mucus, chemokine release, inflammatory cell recruitment and cough and collectively these may be characterized as non-specific irritancy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 healthy
Started Feb 2013
Shorter than P25 for phase_1 healthy
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2013
CompletedFirst Submitted
Initial submission to the registry
February 5, 2013
CompletedFirst Posted
Study publicly available on registry
February 7, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2013
CompletedFebruary 7, 2013
February 1, 2013
2 months
February 5, 2013
February 5, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Cytokine levels (Tumor Necrosis Factor-α and Interleukin-1β)
Two months
Secondary Outcomes (1)
Liver function tests (tB/dB, AST, ALT, ALP)
Two months
Other Outcomes (1)
Adverse events
Two months
Study Arms (4)
ABCD
OTHERABCD A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
BCDA
OTHERBCDA A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
CDAB
OTHERCDAB A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
DABC
OTHERDABC A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
Interventions
Rifampicin, isoniazid, pyrazinamide, and levofloxacin dry powders will be administered to each patient by randomization. Each formulation will be assigned the code, such as A, B, C, or D, and the treatment sequences will be generated as ABCD (sequence 1), BCDA (sequence 2), CDAB (sequence 3) and DABC (sequence 4). On the first day of drug dosing in period I, volunteers will be randomly assigned to a sequence of treatments as indicated in a pre-printed randomization scheme, which was generated using block randomization with block sizes of 4 and 6, and the allocation ratio of 1:1. Subjects will be stratified by sex. Subjects in sequence 1 will receive treatment A during the first study period and will then cross over to receive treatment B, C, and D at the second, third and fourth periods, respectively (each after a 7-day washout period).
Eligibility Criteria
You may qualify if:
- Aged 18-45 years
- Body mass index 18-27 kg/m2
- Healthy
- In the case of reproductive age woman, effective contraceptive will be used for at least 4 weeks prior to a screening examination until the end of study.
- Non-lactating women
- Patients who are willing to participate in the trial and will first sign the informed consent form.
You may not qualify if:
- Allergic to any antituberculosis drugs or other components
- High blood pressure (diastolic pressure \> 90 mmHg)
- Liver enzymes (AST and ALT) \> 2 times of upper normal value
- Pregnancy or lactation
- No underlying diseases such as asthma, COPD, chronic kidney disease, diabetes mellitus, liver disease, immunocompromised deficiency, etc.
- HBsAg positive
- Abnormality in chest X-ray or routine laboratory tests
- Smokers \> 10 cigarette/day or smokers \< 10 cigarettes/day who could not quit at least 7 days before study and throughout study (including the washout between periods)
- Regular alcohol consumption (more than 1 time/week) or alcohol consumption within 7 days prior to the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Songklanagarind Hospital
Hat Yai, Changwat Songkhla, 90112, Thailand
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
February 5, 2013
First Posted
February 7, 2013
Study Start
February 1, 2013
Primary Completion
April 1, 2013
Study Completion
April 1, 2013
Last Updated
February 7, 2013
Record last verified: 2013-02