Pulmonary Multidrug-resistant Tuberculosis (MDR TB) MedDRA version: 9.1 Level: LLT Classification code 10037440 Term: Pulmonary tuberculosis
Conditions
Sponsors
Otsuka Pharmaceutical Development and Commercialization, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Provide written, informed consent prior to all trial-related procedures 2) Male and female patients aged between 18 and 64 years, inclusive. 3) Either mycobacterial culture of sputum positive for growth of M. tuberculosis or sputum smear positive for acid fast bacilli within 60 days from the time of sputum collection for the respective culture or smear until the expected date of enrollment (defined as the date the ICF is signed and screening begins). 4) Patient with TB caused by isolates of M. tuberculosis complex confirmed to be resistant to treatment with isoniazid and rifampicin, or with positive rapid test for rifampicin resistance on direct sputum positive for acid fast bacilli or on culture positive for growth of M. tuberculosis within 60 days prior to the expected date of enrollment performed on sputum samples described above in criterion #3. 5) Findings on chest radiograph consistent with TB. 6) Able to produce sputum for mycobacterial culture. 7) Female patients of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control (for example, two of the following precautions: tubal ligation, vaginal diaphragm, intrauterine device, oral contraceptives, contraceptive implant, combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate) throughout the participation in the trial and for 22 weeks after last dose (to cover duration of ovulation). 8) Male patients must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30weeks after last dose (to cover duration of spermatogenesis). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time. 2) Use of the medications in Section 4.1 including: use of amiodarone at any time during the previous 12 months, use of other anti-arrhthymics for the previous 30 days, and use of certain other medications, including certain anti-depressants, anti-histamines, and macrolides, for the previous 14 days. 3) Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels =265 µmol/L or hepatic impairment characterized by ALT and/or aspartate transferase (AST) levels 3 times the upper limit of the laboratory reference range. 4) Current clinically relevant changes in the screening ECG such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 msec (in both male and female patients), or of QTcF interval over 450 msec in male patients and 470 msec in female patients. 5) Current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction. 6) For patients with HIV infection, CD4 cell count < 350/mm3 or on treatment with anti-retroviral medication for HIV infection. 7) Karnofsky score < 50% 8) Any diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated. 9) Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied). 10) Known or suspected alcohol abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the patient in the opinion of the investigator. 11) Administered an IMP within 1-month prior to Visit 1 (Screening [Days -12 to - 3]). 12) Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form. 13) Recent use of methadone, benzodiazepines, cocaine, amphetamine/metamphetamine, tetrahydrocannabinol, barbiturates, and opiates as determined by a urine drug screen unless evidence is provided that the positive drug screen is the result of authorized medications products prescribed by a physician for a non abuse related indication. 14) Any disorder that in the judgment of the investigator makes the subject not a good candidate for the trial or may prevent the patient from reliably participating in the entire course of the trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: -;Main Objective: To evaluate the safety, efficacy and pharmacokinetics of 200 mg and 400 mg total daily doses of OPC-67683 administered orally as 100 mg twice daily and 200 mg twice daily in comparison to placebo for 56 consecutive days in combination with an optimized background treatment regimen (OBR) to patients with pulmonary, sputum culture-positive MDR TB;Primary end point(s): Efficacy: The primary efficacy endpoint is the proportion of subjects who achieve sputum mycobacterial culture negative for growth using the MGIT? system, ie, sputum culture conversion, within 56 days. Sputum culture conversion is defined to occur at the time of the collection of a sputum specimen with mycobacterial culture negative for growth of M. tuberculosis followed by at least one additional sputum specimen with mycobacterial culture negative for growth at least 27 days after the first specimen and not followed by any sputum specimens with a mycobacterial culture positive for growth of M. tuberculosis at any point during the remainder of the 84-day trial. PK: For OPC-67683, tmax, Cmax, AUC0-24h, ratios of accumulation for Cmax and AUC0-24h [Rac(Cmax) and Rac(AUC), Day 14, 28 or 56/Day 1] will be determined. For OPC-67683 metabolites, tmax, Cmax, AUC0-24h, Rac(Cmax) and Rac(AUC) [Day 14, 28 or 56/Day 1], and t1/2,z will be determined. Safety: Reported adverse events, physical examination, vital signs (blood pressure, heart rate, body temperature and weight), standard 12-lead ECG, clinical laboratory assessment results (hematology, chemistry, urinalysis). | — |
Countries
Estonia, Latvia
Outcome results
None listed