Clinical trial NCT02573350: A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683
Official title: A Phase 2, Multi-center, Uncontrolled, Open-label Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683 as 100 mg BID With Optional Titration to 200 mg BID for up to Six Months Exposure in Patients With Pulmonary Multi-drug Resistant Tuberculosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis, Multidrug-Resistant
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2015-10-09
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Number of Participants With Clinically Significant Abnormality in Vital Signs
timeFrame: From first dose of study drug up to Week 26
measure: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values
timeFrame: From first dose of study drug up to Week 26
measure: Number of Participants With Clinical Significant Abnormality in Laboratory Test
timeFrame: From first dose of study drug up to Week 26
measure: Number of Participants With Abnormality in Audiometry at Baseline
timeFrame: Baseline
measure: Number of Participants With Abnormality in Visual Acuity
timeFrame: From first dose of study drug up to Week 26
measure: Number of Participants With Abnormality in Neurological and Psychiatric Assessment Reported as Treatment-emergent Adverse Event (TEAE)
timeFrame: From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
measure: Number of Participants With Clinical Significant Abnormality in Thyroid Function Test Reported as TEAE
timeFrame: From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
measure: Number of Participants With Any Concomitant Medication Usage
timeFrame: From first dose of study drug up to Week 26
measure: Percentage of Participants With At Least One TEAEs and Serious Adverse Events (SAEs)
timeFrame: From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
measure: Number of Participants With Clinical Significant Abnormality in Coagulation (PT and aPTT) Reported as TEAE
timeFrame: From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
measure: Number of Participants With Clinical Significant Abnormality in Cortisol
timeFrame: From first dose of study drug up to Week 26
Secondary outcomes:
measure: Percentage of Treatment Responders Using the Mycobacterial Growth Indicator Tube (MGIT) Culture System
timeFrame: Week 26
measure: Percentage of Treatment Responders Using Solid Culture Medium
timeFrame: Week 26
measure: Percentage of Treatment Non-responders Using the MGIT Culture System
timeFrame: Week 26
measure: Percentage of Treatment Non-responders Using Solid Culture Medium
timeFrame: Week 26
measure: Percentage of Sustained Converters Using the MGIT Culture System
timeFrame: Week 26
measure: Percentage of Sustained Converters Using Solid Culture Medium
timeFrame: Week 26
measure: Percentage of New Converters Using the MGIT Culture System
timeFrame: Week 26
measure: Percentage of New Converters Using Solid Culture Medium
timeFrame: Week 26
measure: Percentage of Non-converters Using the MGIT Culture System
timeFrame: Week 26
measure: Percentage of Non-converters Using Solid Culture Medium
timeFrame: Week 26
measure: Percentage of Reverters Using the MGIT Culture System
timeFrame: Week 26
measure: Percentage of Reverters Using Solid Culture Medium
timeFrame: Week 26
measure: Percentage of Participants Who Developed Resistance to Delamanid While on Treatment
timeFrame: Up to Week 26
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chest Hospital
city: Tallinn
country: Estonia
facility: North Estonian Medical Centre Foundation Center of Pulmonology
city: Tartu
country: Estonia
facility: Tartu University Lung Hospital
city: Seoul
country: Korea, Republic of
facility: Younsei University Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Riga
country: Latvia
facility: State Agency of Tuberculosis and Lung Disease
city: Lima
country: Peru
facility: Hospital Nacional Sergio E. Bernales
city: Makati City
country: Philippines
facility: Tropical Disease Foundation
Study officials:
References: