A Placebo-controlled, Phase 2 Trial to Evaluate OPC 67683 in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB)

• Status: Completed
• Trial end date: 2010-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a clinical trial to evaluate the safety and efficacy of OPC-67683 in the treatment of multidrug resistant tuberculosis (MDR TB) for 56 days. In addition to an optimized background regimen (OBR).patients will receive will be randomized to:

• 100 mg OPC-67683 BID

• 200 mg OPC-67683 BID

• placebo BID After 56 days subjects will complete their OBR.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Criteria

Inclusion Criteria:

• Provide written, informed consent prior to all trial-related procedures

• Male and female patients aged between 18 and 64 years, inclusive.

• Either mycobacterial culture of sputum positive for growth of M. tuberculosis or sputum smear positive for acid fast bacilli within 60 days prior to the expected date of enrollment.

• 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 within 60 days prior to the expected date of enrollment.

• Findings on chest radiograph consistent with TB.

• Able to produce sputum for mycobacterial culture.

• 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).

• 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).

Exclusion Criteria:

• A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time.

• Use of the medications in Section 4.1 of the protocol including: use of amiodarone at any time during the previous 12 months, use of other anti-arrhythmics for the previous 30 days, and use of certain other medications, including certain anti-depressants, anti-histamines, and macrolides, for the previous 14 days.

• Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels ≥265 micromol/L or hepatic impairment characterized by ALT and/or aspartate transferase (AST) levels 3 times the upper limit of the laboratory reference range.

• Current clinically relevant changes in the ECG such as any 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.

• Current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction.

• For patients with HIV infection, CD4 cell count < 350/mm3 or on treatment with anti-retroviral medication for HIV infection.

• Karnofsky score < 60%.

• Any diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated.

• Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied).

• 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.

• Administered an IMP within 1 month prior to Visit 1 (Screening [Days -9 to -3]).

• Pregnant, 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 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.

• 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.