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-EE
• Lead Sponsor: Otsuka Pharmaceutical Development and Commercialization, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-12-11
• Last Update Posted: 19 March 2012

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 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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified