Safety and Efficacy Trial of Delamanid for 6 Months in Participants With Multidrug-resistant Tuberculosis

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Trial to Evaluate the Safety and Efficacy of Delamanid (OPC-67683) Administered Orally as 200 mg Total Daily Dose for Six Months in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis

The purpose of this trial is to determine whether delamanid is effective in the treatment of multidrug-resistant tuberculosis (MDR TB) in combination with other MDR TB medications during 6 months of treatment.

The primary objective of this trial is to evaluate the efficacy of delamanid administered orally as 100 milligrams (mg) twice daily (BID) for 2 months followed by 200 mg once daily (QD) for 4 months in combination with an optimized background treatment regimen (OBR) versus placebo with OBR during the 6-month Intensive Period of MDR TB treatment. Following the 6-month Intensive Period, OBR was administered alone during the Continuation Period for 12 to 18 months (from Month 7 up to Month 24). The trial also included a post-treatment follow-up period of 6 to 12 months (Month 19 to Month 24 to the end of Month 30). OBR given throughout the study was administered as per World Health Organization (WHO) guidelines and national treatment norms.

This trial is a multicenter, randomized, double-blind, stratified, placebo-controlled trial that was conducted globally in 2 parallel groups at 17 sites in 7 countries qualified to treat MDR TB.

Inclusion Criteria:

• Provide written, informed consent
• Current diagnosis of MDR TB
• Chest radiograph consistent with TB
• Able to produce sputum
• Negative urine pregnancy test and agree to use a highly effective method of birth control and/or adequate method of contraception

Exclusion Criteria:

• Allergy to any nitro-imidazoles or nitro-imidazole derivates
• Diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated
• Use of disallowed medications
• Renal impairment
• Abnormal electrocardiogram (ECG) results
• Cardiovascular disorders
• Body mass index (BMI) < 16 kg/m^2
• Karnofsky score < 50%
• Significant metabolic, gastrointestinal, neurological, psychiatric, or endocrine diseases, active malignancy
• Alcohol abuse
• Pregnant, breast-feeding, or planning to conceive or father a child
• Recent use of methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, tetrahydrocannabinol, barbiturates, and opiates
• Previous exposure to delamanid
• Administered an investigational medicinal product (IMP) within 1 month prior to Screening (Days -21 to -2).
• Evidence of extensively drug-resistant TB based on the definition from WHO
• Human immunodeficiency virus (HIV) co-infection for participants screened at sites not participating in the HIV subtrial (data from the HIV subtrial will be reported separately from the Clinical Study Report for Study 242-09-213).