A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683
Condition: Tuberculosis, Multidrug-Resistant
MeSH terms: Tuberculosis; Tuberculosis, Multidrug-Resistant
Intervention: Delamanid; OBR
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. Study investigators could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 213.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No

Summary:

      A phase 2, multicenter, uncontrolled, open-label trial in participants with Multi-drug
      Resistant Tuberculosis (MDR-TB). Only participants who completed Trial 242-07-204
      (NCT00685360) were eligible. The trial was performed globally at 14 sites qualified to treat
      MDR-TB. All 434 participants who completed Trial 242-07-204 were eligible for this trial if
      there was still potential clinical benefit to them and all inclusion criteria and no
      exclusion criteria were met.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provide written, informed consent prior to all trial-related procedures

          -  Male or female participants aged between 18 and 64 years, inclusive, at the time of
             enrollment into the 242-07-204 trial. Participants who were 64 years at the time of
             204 enrollment and who are now 65 years, are eligible for this trial.

          -  Participants who have completed trial 242-07-204

          -  Participants judged by the investigator to have the potential for clinical benefit
             from OPC-67683 exposure

          -  Able to produce sputum for mycobacterial culture or able to obtain sputum produced
             through induction

          -  Female participants of childbearing potential must have a negative urine pregnancy
             test and agree to use a highly effective method of birth control throughout the
             participation in the trial and for 22 weeks after last dose.

          -  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.

        Exclusion Criteria:

          -  Greater than 30 days has elapsed from the participant'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.

          -  A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time.

          -  Use of the medications in Section 5.4.7 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 moles per liter (mol/L) or hepatic impairment characterized by
             Alanine aminotransferase (ALT) and/or aspartate transferase (AST) levels 3 times the
             upper limit of the laboratory reference range from the screening lab results.

          -  Current clinically relevant changes in the electrocardiogram (ECG) (between Trial
             242-07-204 Day 56 assessment and baseline) such as any atrioventricular (AV) block,
             prolongation of the QRS complex over 120 milliseconds (msec) (in both male and female
             participants), or the corrected QT interval using Fridericia's method (QTcF) interval
             over 450 msec in male participants and 470 msec in female participants.

          -  Current clinically relevant cardiovascular disorders such as heart failure, coronary
             artery disease, uncontrolled or poorly controlled hypertension, arrhythmia,
             tachyarrhythmia or status after myocardial infarction.

          -  Any participants with known or reported significant psychiatric history.

          -  For participants with human immunodeficiency virus (HIV) infection, CD4 cell count
             less than 350/cubic millimeter (mm^3) or on treatment with antiretroviral medication
             for HIV infection.

          -  Karnofsky score under 50 percent (%) while hospitalized and less than 60% while not
             hospitalized.

          -  Any current 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 participants in the opinion of the investigator.

          -  Administered an investigational medicinal product (IMP) within 1 month prior to Visit
             1 other than OPC-67683 given as IMP in trial 242-07-204.

          -  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/methamphetamine,
             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.

          -  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.