A Trial to Evaluate OPC 67683 in Participants With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB)
Condition: Tuberculosis, Pulmonary; Tuberculosis, Multidrug Resistant; Extensively Drug-Resistant Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Extensively Drug-Resistant Tuberculosis
Intervention: Delamanid; Optimized Background Regimen (OBR); Placebo
Intervention description: Delamanid was administered orally twice daily as 50-mg tablets under fed conditions in the morning and evening.; Selection and administration of the treatment medications (i.e., OBRs) was based on World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country.
Study Investigator could change OBR for a participant based on participant's tolerability and drug susceptibility testing (DST) results.; Placebo tablets matching 50-mg tablets of delamanid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 481.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Tuberculosis; Pulmonary; Multidrug resistant; Antitubercular Agents; OPC 67683

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), participants will be randomized to receive:

        -  100 mg OPC-67683 twice daily (BID)

        -  200 mg OPC-67683 BID

        -  Placebo BID

      After 56 days participants will complete their optimized background regimen (OBR).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provide written, informed consent prior to all trial-related procedures

          -  Male and female participants aged between 18 and 64 years, inclusive.

          -  Either mycobacterial culture of sputum positive for growth of Mycobacterium
             tuberculosis or sputum smear positive for acid fast bacilli within 60 days prior to
             the expected date of enrollment.

          -  Participant with TB caused by isolates of Mycobacterium 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 participants 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 participants must agree to use an adequate method of contraception (double
             barrier) throughout the participation in the trial and for 30 weeks 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 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 alanine
             transaminase (ALT) and/or aspartate transferase (AST) levels 3 times the upper limit
             of the laboratory reference range.

          -  Current clinically relevant changes in the electrocardiogram (ECG) such as any
             atrioventricular (AV) block, prolongation of the QRS complex over 120 milliseconds (in
             both male and female participants), or of either the QT interval corrected by
             Fridericia's formula (QTcF) or QT interval corrected by Bazett's formula (QTcB)
             interval over 430 milliseconds in male participants and 450 milliseconds in female
             participants.

          -  Current clinically relevant cardiovascular disorder such as heart failure, coronary
             heart disease, hypertension, arrhythmia, tachyarrhythmia or status after myocardial
             infarction.

          -  For participants with human immunodeficiency virus (HIV) infection, cluster of
             differentiation 4 helper/inducer T cell[s] (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 participant in the opinion of the investigator.

          -  Administered an investigational medicinal product (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 participant not a good
             candidate for the trial or may prevent the participant from reliably participating in
             the entire course of the trial.