A Phase 2, Multi-center, Uncontrolled, Open-label Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2015
• Main ID: NCT02573350
• Date of registration: 29/09/2015
• Prospective Registration: No
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: A Phase 2, Multi-center, Uncontrolled, Open-label Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683
• Scientific 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
• Date of first enrolment: March 2009
• Target sample size: 213
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02573350
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

China, Estonia, Korea, Republic of, Latvia, Peru, Philippines

Key inclusion & exclusion criteria

Inclusion Criteria:

- Provide written, informed consent prior to all trial-related procedures

- Male or female patients aged between 18 and 64 years, inclusive, at the time of
enrollment into the 242-07-204 trial. Patients who were 64 years at the time of 204
enrollment and who are now 65 years, are eligible for this trial.

- Patients who have completed trial 242-07-204

- Patients 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 patients 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 patients must agree to use an adequate method of contraception (double barrier)
throughout the participation in the trial and for 30weeks after last dose.

Exclusion Criteria:

- Greater than 30 days has elapsed from the patient'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

- 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 mol/L or hepatic impairment characterized by 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 ECG (between Trial 204 day 56 assessment
and baseline) such as any atrioventricular (AV) block, prolongation of the QRS
complex over 120 msec (in both male and female patients), or the QTcF interval over
450 msec in male patients and 470 msec in female patients.

- Current clinically relevant cardiovascular disorder such as heart failure, coronary
artery disease, uncontrolled or poorly controlled hypertension, arrhythmia,
tachyarrhythmia or status after myocardial infarction.

- Any patients with known or reported significant psychiatric history.

- For patients with HIV infection, CD4 cell count less than 350/mm3 or on treatment
with antiretroviral medication for HIV infection.

- Karnofsky score under 50% 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 patient in the opinion of the investigator.

- Administered an 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 patient not a good
candidate for the trial or may prevent the patient from reliably participating in the
entire course of the trial.



Age minimum: 18 Years
Age maximum: 64 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Tuberculosis, Multidrug-Resistant

Intervention(s)

Drug: Delamanid

Primary Outcome(s)

Adverse Events [Time Frame: Baseline, Day 1, Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26 and Follow-up]

Subjects with changes in ECG reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Day 1, Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26]

Subjects with changes in vital signs reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Day 1, Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26]

Subjects with changes in Hematology, chemistry, and urinalysis assessments reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Weeks 4, 10, 14, 18, 22, 26]

Subjects with changes in Neurological and psychiatric assessments reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26]

Subjects with changes in audiometry reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Day 1, Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26]

Subjects with changes in cortisol reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Weeks 4, 10, 14, 18, 22, 26]

Subjects with changes in Coagulation (PT and aPTT) reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Weeks 4, 10, 14, 18, 22, 26]

Subjects with changes in Visual acuity reported as Treatment Emergent Adverse Events [Time Frame: Baseline, Weeks 1, 2, 4, 6, 10, 14, 18, 22, 26]

Secondary Outcome(s)

Proportion of Sustained Converters using the MGIT culture system. [Time Frame: 6 months]

Proportion of Treatment Responders using the MGIT culture system. [Time Frame: 6 months]

Proportion of New Converters using solid culture medium. [Time Frame: 6 months]

Proportion. of Non-converters using solid culture medium. [Time Frame: 6 months]

Proportion of Reverters using the MGIT culture system. [Time Frame: 6 months]

Proportion of New Converters using the MGIT culture system. [Time Frame: 6 months]

Proportion of Treatment Responders using solid culture medium. [Time Frame: 6 months]

Proportion. of patients who develop resistance to delamanid while on treatment at any visit. [Time Frame: 6 months]

Proportion of Reverters using solid culture medium. [Time Frame: 6 months]

Proportion of Sustained Converters using solid culture medium. [Time Frame: 6 months]

Proportion of Treatment Non-responders using the MGIT culture system. [Time Frame: 6 months]

Proportion of Non-converters using the MGIT culture system. [Time Frame: 6 months]

Proportion of Treatment Non-responders using solid culture medium. [Time Frame: 6 months]

Secondary ID(s)

242-07-208

Source(s) of Monetary Support

Please refer to primary and secondary sponsors