E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Multidrug-resistant Tuberculosis |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037440 |
E.1.2 | Term | Pulmonary tuberculosis |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of orally administered OPC-67683 when administered two times daily (BID) to MDR TB patients refractory to treatment with an optimized background regimen of anti-TB medications (OBR). To evaluate the pharmacokinetics (PK) of OPC-67683 and metabolites. |
|
E.2.2 | Secondary objectives of the trial |
To determine the proportion of patients with sputum culture conversion. Sputum culture conversion is defined to occur at the time of the collection of a sputum specimen with mycobacterial culture negative for growth of MTB using the MGIT® (Mycobacteria Growth Indicator Tube) culture system followed by at least one additional sputum specimen negative for growth at least 28 days after the first specimen negative for growth and not followed by any sputum specimens positive for growth of MTB during the remainder of the 280-day (40-week) trial period. To monitor development of in vitro resistance to OPC-67683 among enrolled patients over the 196-day (28-week) Treatment Period of the trial. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with at least three sputum mycobacterial cultures positive for MTB with in vitro resistance to isoniazid and rifampicin collected at separate timepoints during the previous 270 days (9 months) despite treatment with first and second-line anti-TB drugs, including one culture within the previous 60 days prior to date of screening initiation.
Patients with sputum mycobacterial culture positive for MTB with in vitro susceptibility to at least one anti-TB medication within the previous 60 days prior to date of screening initiation. |
|
E.4 | Principal exclusion criteria |
A history of allergy to any nitro-imidazoles or nitroimidazole derivates.
Prohibited medications: use of amiodarone for the previous 12 months, use of other anti-arrhthymics for the previous 30 days, and use of certain other medications, including certain anti-depressants, anti-histamines, and macrolides, for the previous 14 days.
Current clinically relevant changes in the screening ECG such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 milliseconds (in both male and female patients), or of QTcF interval over 450 milliseconds in male patients and over 470 milliseconds in female patients.
Current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, uncontrolled or poorly controlled hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction.
For patients with HIV infection, CD4 cell count < 350/mm3 or on treatment with anti-retroviral medication for HIV infection.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety: Vital signs, ECGs, clinical laboratory assessments, and AEs.
Pharmacokinetic: For OPC-67683, time to maximal peak plasma concentration (tmax), maximal peak plasma concentration (Cmax), area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24h), ratios of accumulation for Cmax and AUC0-24h [Rac(Cmax) and Rac(AUC), Day 14, 28, 56, 112 or 196/Day 1]. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The End of Trial Date is defined as the last Date of Contact or the Date of Final Contact Attempt from the Post-treatment Follow-up case report form (CRF) page for the last subject completing or withdrawing from the trial.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |