Safety, Efficacy and Pharmacokinetics of OPC-67683 in Patients With Pulmonary Tuberculosis
Primary Purpose
Pulmonary Tuberculosis
Status
Completed
Phase
Phase 2
Locations
South Africa
Study Type
Interventional
Intervention
OPC-67683
Rifafour e-275
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Tuberculosis
Eligibility Criteria
Inclusion Criteria:
- Provide written, informed consent prior to all trial-related procedures.
- Male and female patients aged between 18 and 64 years, inclusive.
- Newly diagnosed, previously untreated, uncomplicated, smear positive, pulmonary TB.
- A chest X-ray finding compatible with TB.
- Sputum positive on direct microscopy for acid-fast bacilli (AFB) (at least 1+).
- Able to produce an adequate volume of sputum (10mL or more estimated overnight production).
- Female patients of childbearing potential must demonstrate a negative pregnancy test result. Furthermore they must agree to use a highly effective method of contraception.
- Male patients must agree to use an adequate method of contraception.
Exclusion Criteria:
- Poor general condition where no delay in treatment can be tolerated or where immediate hospital admission is warranted.
- Rifampicin-resistant bacteria detected in the sputum susceptibility testing at Screening.
- Treatment received with any drug active against M. tuberculosis within the 3 months prior to Screening.
- History of allergy to any nitro-imidazole derivates, rifamycin derivatives, isoniazid derivatives, pyrazinamide or ethambutol.
- Clinical evidence of severe extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis).
- Evidence of pulmonary silicosis, lung fibrosis, or other lung condition considered as severe by the investigator (other than TB).
- Presence of chronic obstructive pulmonary disease or asthma.
- Any clinically relevant concomitant conditions or renal impairment characterized by serum creatinine levels >= 1.5xULN or hepatic impairment or alcohol abuse characterized by ALT and/or aspartate transferase (AST) levels 3xULN and/or gamma-glutamyl transpeptidase (GGT) levels 3xULN of the laboratory reference range.
- Known or suspected alcohol or drug abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the patient, in the opinion of the investigator, and as evident by a positive urine drug screen.
- Neuropathy, psychosis or epilepsy.
- Clinically relevant changes in the ECG such as atrioventricular (AV) block, prolongation of the QRS complex >120 milliseconds (in both male and female patients), or QTcB interval >430 milliseconds in male patients and >450 milliseconds in female patients. Family history of long QT syndromes and/or Torsade de Pointes.
- History of or current clinically relevant cardiovascular disorder such as hypokalaemia, heart failure, coronary heart disease, hypertension, arrhythmia or symptom strongly suggestive of such a problem (for example, syncope or palpitations), tachyarrhythmia or status after myocardial infarction.
- Known bleeding disorders or family history of bleeding disorders.
- Diabetes treated with insulin.
- Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
- Any diseases or conditions in which the use of rifampicin, isoniazid, pyrazinamide or ethambutol is contra-indicated.
- Any disease or conditions in which any of the medicinal products listed in the protocol, is used. Treatment received with quinolones and prednisolone within 3 months prior to Screening.
- Administration of an IMP within 1 month prior to Screening.
- Pregnancy, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form.
- Recent use of methadone, benzodiazepines, cocaine, amphetamine/metamphetamine, tetrahydrocannabinol, barbiturates, tricyclic antidepressants, and opiates as determined by a urine drug screen.
- Helper/inducer T lymphocyte (CD4 cell) count of <=350x106/L.
- Use of antiretroviral therapy.
Sites / Locations
- Tiervlei Trial Center, Karl Bremer Hospital
- University of Cape Town Lung Institute
- Medical Research Council
Outcomes
Primary Outcome Measures
TB bacterial load in sputum measured as colony forming units
Secondary Outcome Measures
Early Bactericidal Activity (EBA)
Slope 0-14
Tme to culture positivity
Full Information
NCT ID
NCT00401271
First Posted
November 17, 2006
Last Updated
March 6, 2007
Sponsor
Otsuka Frankfurt Research Institute GmbH
1. Study Identification
Unique Protocol Identification Number
NCT00401271
Brief Title
Safety, Efficacy and Pharmacokinetics of OPC-67683 in Patients With Pulmonary Tuberculosis
Official Title
A Phase II Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Four Oral Doses of OPC-67683 in Patients With Uncomplicated, Smear-Positive, Pulmonary Tuberculosis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2007
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2007 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Otsuka Frankfurt Research Institute GmbH
4. Oversight
5. Study Description
Brief Summary
The purpose of this trial is to evaluate the safety, efficacy and pharmacokinetics of 100mg, 200mg , 300mg and 400mg once daily of OPC-67683, administered orally for 14 consecutive days, in patients with uncomplicated, smear-positive pulmonary TB.
The four OPC-67683 treatment groups will comprise 12 patients each and the one standard therapy (Rifafour e-275) group six patients.
Trial 242-06-101 is an exploratory and not a confirmatory trial and as such no hypothesis will be tested statistically.
The control group, six patients treated with Rifafour, will serve as an control to confirm the microbiological assessments during the trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Tuberculosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
OPC-67683
Intervention Type
Drug
Intervention Name(s)
Rifafour e-275
Primary Outcome Measure Information:
Title
TB bacterial load in sputum measured as colony forming units
Secondary Outcome Measure Information:
Title
Early Bactericidal Activity (EBA)
Title
Slope 0-14
Title
Tme to culture positivity
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provide written, informed consent prior to all trial-related procedures.
Male and female patients aged between 18 and 64 years, inclusive.
Newly diagnosed, previously untreated, uncomplicated, smear positive, pulmonary TB.
A chest X-ray finding compatible with TB.
Sputum positive on direct microscopy for acid-fast bacilli (AFB) (at least 1+).
Able to produce an adequate volume of sputum (10mL or more estimated overnight production).
Female patients of childbearing potential must demonstrate a negative pregnancy test result. Furthermore they must agree to use a highly effective method of contraception.
Male patients must agree to use an adequate method of contraception.
Exclusion Criteria:
Poor general condition where no delay in treatment can be tolerated or where immediate hospital admission is warranted.
Rifampicin-resistant bacteria detected in the sputum susceptibility testing at Screening.
Treatment received with any drug active against M. tuberculosis within the 3 months prior to Screening.
History of allergy to any nitro-imidazole derivates, rifamycin derivatives, isoniazid derivatives, pyrazinamide or ethambutol.
Clinical evidence of severe extrathoracic TB (miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis).
Evidence of pulmonary silicosis, lung fibrosis, or other lung condition considered as severe by the investigator (other than TB).
Presence of chronic obstructive pulmonary disease or asthma.
Any clinically relevant concomitant conditions or renal impairment characterized by serum creatinine levels >= 1.5xULN or hepatic impairment or alcohol abuse characterized by ALT and/or aspartate transferase (AST) levels 3xULN and/or gamma-glutamyl transpeptidase (GGT) levels 3xULN of the laboratory reference range.
Known or suspected alcohol or drug abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the patient, in the opinion of the investigator, and as evident by a positive urine drug screen.
Neuropathy, psychosis or epilepsy.
Clinically relevant changes in the ECG such as atrioventricular (AV) block, prolongation of the QRS complex >120 milliseconds (in both male and female patients), or QTcB interval >430 milliseconds in male patients and >450 milliseconds in female patients. Family history of long QT syndromes and/or Torsade de Pointes.
History of or current clinically relevant cardiovascular disorder such as hypokalaemia, heart failure, coronary heart disease, hypertension, arrhythmia or symptom strongly suggestive of such a problem (for example, syncope or palpitations), tachyarrhythmia or status after myocardial infarction.
Known bleeding disorders or family history of bleeding disorders.
Diabetes treated with insulin.
Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).
Any diseases or conditions in which the use of rifampicin, isoniazid, pyrazinamide or ethambutol is contra-indicated.
Any disease or conditions in which any of the medicinal products listed in the protocol, is used. Treatment received with quinolones and prednisolone within 3 months prior to Screening.
Administration of an IMP within 1 month prior to Screening.
Pregnancy, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form.
Recent use of methadone, benzodiazepines, cocaine, amphetamine/metamphetamine, tetrahydrocannabinol, barbiturates, tricyclic antidepressants, and opiates as determined by a urine drug screen.
Helper/inducer T lymphocyte (CD4 cell) count of <=350x106/L.
Use of antiretroviral therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas H Diacon, Dr.
Organizational Affiliation
Tiervlei Trial Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Roxana Rustomjee, Dr.
Organizational Affiliation
Medical Research Council
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rodney Dawson, Dr.
Organizational Affiliation
University of Cape Town Lung Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tiervlei Trial Center, Karl Bremer Hospital
City
Bellville
State/Province
W Cape
ZIP/Postal Code
7531
Country
South Africa
Facility Name
University of Cape Town Lung Institute
City
Mowbray
State/Province
W Cape
ZIP/Postal Code
7700
Country
South Africa
Facility Name
Medical Research Council
City
Durban
ZIP/Postal Code
4000
Country
South Africa
12. IPD Sharing Statement
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Safety, Efficacy and Pharmacokinetics of OPC-67683 in Patients With Pulmonary Tuberculosis
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