A Multi center, Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Doses of OPC-67683 in Patients with Pulmonary Sputum Culture-Positive, Multidrug-resistant Tuberculosis

Conditions: Pulmonary Multidrug-resistant Tuberculosis (MDR TB)
MedDRA version: 9.1Level: LLTClassification code 10037440Term: Pulmonary tuberculosis

Registration Number: EUCTR2007-005229-31-LV

Lead Sponsor: Otsuka Pharmaceutical Development and Commercialization, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 201

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 or sputum smear
positive for acid fast bacilli with a positive rapid test for rifampicin resistance on
direct sputum within 60 days prior to the expected date of enrollment.
4) Patient with TB caused by isolates of M. tuberculosis complex confirmed to be
resistant to treatment with isoniazid and rifampicin, or positive rapid test for
rifampicin resistance.
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
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

1) A history of allergy to any nitro-imidazoles or nitro-imidazole derivates.
2) Use of the medications in Section 4.1 including: use of amiodarone for the
previous 12 months, use of other anti-arrhthymics for the previous 30 days, and
use of certain other medications, including certain anti-depressants, antihistamines,
and macrolides, for the previous 14 days.
3) Any 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) Clinically relevant changes in the ECG such as atrioventricular (AV) block,
prolongation of the QRS complex over 120 milliseconds (in both male and female
patients), or of either the QTcF or QTcB interval over 430 milliseconds in male
patients and 450 milliseconds 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 < 60%.
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 -9 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, tricyclic
antidepressants, 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.