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The Safety of Tuberculosis Treatments by Oral Inhalation

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ClinicalTrials.gov Identifier: NCT01785927
Recruitment Status : Unknown
Verified February 2013 by Teerapol Srichana, Prince of Songkla University.
Recruitment status was:  Not yet recruiting
First Posted : February 7, 2013
Last Update Posted : February 7, 2013
Sponsor:
Collaborator:
National Research Council of Thailand
Information provided by (Responsible Party):
Teerapol Srichana, Prince of Songkla University

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.


Condition or disease Intervention/treatment Phase
Healthy Other: ABCD Phase 1

Detailed Description:
Four formulations of antituberculosis drug (rifampicin, isoniazid, pyrazinamide, and levofloxacin) 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Clinical Trial Phase I of Antituberculosis Dry Powder Aerosols
Study Start Date : February 2013
Estimated Primary Completion Date : April 2013
Estimated Study Completion Date : April 2013

Arm Intervention/treatment
ABCD
ABCD A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
Other: ABCD
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).

BCDA
BCDA A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
Other: ABCD
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).

CDAB
CDAB A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
Other: ABCD
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).

DABC
DABC A = rifampicin, B = isoniazid, C= pyrazinamide, D = levofloxacin
Other: ABCD
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).




Primary Outcome Measures :
  1. Cytokine levels (Tumor Necrosis Factor-α and Interleukin-1β) [ Time Frame: Two months ]

Secondary Outcome Measures :
  1. Liver function tests (tB/dB, AST, ALT, ALP) [ Time Frame: Two months ]

Other Outcome Measures:
  1. Adverse events [ Time Frame: Two months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01785927


Contacts
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Contact: Teerapol Srichana, PhD 66-74-288979 teerapol.s@psu.ac.th

Locations
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Thailand
Songklanagarind Hospital Not yet recruiting
Hat Yai, Songkla, Thailand, 90112
Contact: Siwasak Juthong, MD    66-74-451474    jsiwasak@medicine.psu.ac.th   
Sub-Investigator: Siwasak Juthong, MD         
Sponsors and Collaborators
Prince of Songkla University
National Research Council of Thailand

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Responsible Party: Teerapol Srichana, Associate Professor, Prince of Songkla University
ClinicalTrials.gov Identifier: NCT01785927     History of Changes
Other Study ID Numbers: RES.no. 18/2554
First Posted: February 7, 2013    Key Record Dates
Last Update Posted: February 7, 2013
Last Verified: February 2013
Keywords provided by Teerapol Srichana, Prince of Songkla University:
Antituberculosis
Dry powder aerosols
Inhalation
Additional relevant MeSH terms:
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Levofloxacin
Isoniazid
Pyrazinamide
Antitubercular Agents
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Anti-Bacterial Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents