A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683

Otsuka

Status and phase: Completed; Phase 2

Conditions: Tuberculosis, Multidrug-Resistant

Treatments: Drug: Delamanid; Drug: OBR

Study type: Interventional

Funder types: Industry

Identifiers

NCT02573350

242-07-208

2008-005107-26 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 213 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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213 participants in 2 patient groups

Delamanid 100 mg BID + OBR

Experimental group

Description:

Participants received Delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) along with at least 4 additional anti-TB medications per optimized background regimen (OBR) from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.

Treatment:

Drug: OBR

Drug: Delamanid

Delamanid 200 mg BID + OBR

Experimental group

Description:

Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.

Treatment:

Drug: OBR

Drug: Delamanid