A Phase 2, Multi-center, Uncontrolled, Open-label Trial to Evaluate Safety, tolerability, and Efficacy of Orally Administered OPC-67683 as 100 mg BID with optional titration to 200 mg BID for up to Six Months Exposure in Patients with Pulmonary Multi-drug Resistant Tuberculosis

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

Registration Number: EUCTR2008-005107-26-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: 430

Inclusion Criteria

1) Provide written, informed consent prior to all trial-related procedures
2) Male or female patients aged between 18 and 64 years, inclusive, at the time of
enrollment into the 242-07-204 trial. Patients who were 64 years at the time of
204 enrollment and who are now 65 years, are eligible for this trial.
3) Patients who have completed trial 242-07-204.
4) Patients judged by the investigator to have the potential for clinical benefit from
OPC-67683 exposure.
5) Able to produce sputum for mycobacterial culture or able to obtain sputum
produced through induction.
6) 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.
7) 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.
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) Greater than 30 days has elapsed from the patient’s date of completion in the 242-
07-204 trial or greater than 30 days has elapsed since the patient’s trial
investigator’s site was initiated in this trial, whichever is later.
2) A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any
time.
3) 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.
4) 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 from the screening lab results.
5) Current clinically relevant changes in the ECG (between Trial 204 day 56
assessment and baseline) such as any atrioventricular (AV) block, prolongation of
the QRS complex over 120 msec (in both male and female patients), or the QTcF
interval over 450 msec in male patients and 470 msec in female patients.
6) Current clinically relevant cardiovascular disorder such as heart failure, coronary
artery disease, uncontrolled or poorly controlled hypertension, arrhythmia,
tachyarrhythmia or status after myocardial infarction.
7) Any patients with known or reported significant psychiatric history.
8) For patients with HIV infection, CD4 cell count < 350/mm3 or on treatment with
anti-retroviral medication for HIV infection.
9) Karnofsky score < 50% while hospitalized and <60% while not hospitalized.
10) Any current diseases or conditions in which the use of nitro-imidazoles or nitroimidazole
derivates is contra-indicated.
11) Evidence of clinically significant metabolic, gastrointestinal, neurological,
psychiatric or endocrine diseases, malignancy, or other abnormalities (other than
the indication being studied).
12) 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.
13) Administered an IMP within 1-month prior to Visit 1 other than OPC-67683
given as IMP in trial 242-07-204.
14) Pregnant, breast-feeding, or planning to conceive or father a child within the
timeframe described in the informed consent form.
15) 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 or products prescribed by a
physician for a non-abuse related indication.
16) Any disorder that in the judgment of the investigator makes the patient not a good
candidate for the trial or may prevent the patient from reliably participating in the
entire course of the trial.