Safety and Pharmacokinetics (PK) in Multidrug-Resistant (MDR) Refractive Tuberculosis

NCT ID: NCT01131351

Last Updated: 2021-11-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-19
• Study Completion Date: 2011-05-12

Brief Summary

The purpose of this study is:

• To evaluate the safety and tolerability of orally administered OPC-67683 when administered two times daily to MDR tuberculosis (TB) participants refractory to treatment with an optimized background regimen of anti-TB medications (OBR).
• To evaluate the pharmacokinetics (PK) of OPC-67683 and metabolites.

Conditions

Tuberculosis

Keywords

MDR-TB; Dose Escalation; Phase II; Open Label; Non Controlled; Pulmonary Multidrug-Resistant Tuberculosis (MDR TB)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Delamanid 250 mg BID+ OBR

Participants received delamanid five 50 milligrams (mg) (250 mg) tablets, twice a day (BID), along with at least 2 additional anti-TB medications per optimized background regimen (OBR) for up to 28 weeks.

Group Type: EXPERIMENTAL

Delamanid

Intervention Type: DRUG

OPC-67683 film-coated tablets

Optimized Background Regimen (OBR)

Intervention Type: DRUG

OBR was selected at the discretion of the study investigator and included at least 2 anti-TB medications based on World Health Organization (WHO's) guidelines for the programmatic management of drug-resistant TB. Study investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.

Delamanid 300 mg BID+ OBR

Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.

Group Type: EXPERIMENTAL

Delamanid

Intervention Type: DRUG

OPC-67683 film-coated tablets

Optimized Background Regimen (OBR)

Intervention Type: DRUG

OBR was selected at the discretion of the study investigator and included at least 2 anti-TB medications based on World Health Organization (WHO's) guidelines for the programmatic management of drug-resistant TB. Study investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.

Interventions

Delamanid

OPC-67683 film-coated tablets

Intervention Type: DRUG

Optimized Background Regimen (OBR)

OBR was selected at the discretion of the study investigator and included at least 2 anti-TB medications based on World Health Organization (WHO's) guidelines for the programmatic management of drug-resistant TB. Study investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.

Intervention Type: DRUG

Other Intervention Names

OPC-67683

Eligibility Criteria

Inclusion Criteria

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

2. Male or female participants aged between 18 and 64 years, inclusive.

3. Able to produce sputum for mycobacterium culture or able to obtain sputum produced through Induction.

4. At least three sputum mycobacterium cultures positive for MTB with in-vitro resistance to isoniazid and rifampicin during the previous 270 days (9 months) despite treatment with first and second line anti-TB drugs, including one positive culture within the previous 60 days from the time of sputum collection, prior to date of screening initiation [defined as the date the informed consent form (ICF) is signed and screening begins].

5. Sputum mycobacterial culture positive for MTB with in-vitro susceptibility to at least one anti-TB medication within the previous 60 days prior to the date of screening initiation.

6. Participant judged by the investigator to have potential for clinical benefit from OPC-67683 exposure.

7. Female participants of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control (for example, two of the following precautions: tubal ligation, vaginal diaphragm, intrauterine device, oral contraceptives, contraceptive implant, combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate) throughout the participation in the trial and for 22 weeks after last dose (to cover duration of ovulation).

8. Male participant must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30 weeks after last dose (to cover duration of spermatogenesis).

Exclusion Criteria

1. A history of allergy to any nitro-imidazoles or nitro-imidazole derivatives at any time.

2. Use of the medications in Section 4.1 including: use of amiodarone at any time during the previous 12 months, use of other antiarrhythmics for the previous 30 days, as well as use of certain antidepressants, anti-histamines, any macrolides, for the previous 14 days.

3. Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels ~265 micromoles (μmol)/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.

4. Current clinically relevant changes in the Screening electrocardiogram (ECG) such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 msec (in both male and female participants), or of the QT interval with Fridericia's correction (QTcF) interval over 450 msec in male participants and over 470 msec in female participants.

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

6. For participants with human immunodeficiency virus (HIV) infection, helper/inducer T-lymphocyte (CD4 cell) count < 350/mm^3 or on treatment with anti-retroviral medication for HIV infection.

7. Karnofsky score < 50%.

8. Any current diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Infectology Center of Latvia - Clinic of Tuberculosis and Lung Diseases

Ogre, , Latvia

Hospital for Tuberculosis and Lung Diseases

Šiauliai, , Lithuania

National Tuberculosis and Infectious Diseases University Hospital

Vilnius, , Lithuania

Countries

Latvia; Lithuania

Other Identifiers

2009-014944-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

242-08-210

Identifier Type: -

Identifier Source: org_study_id