Clinical trial NCT00685360
Conditions: Tuberculosis, Pulmonary Tuberculosis, Multidrug Resistant Extensively Drug-Resistant Tuberculosis
Keywords: Tuberculosis Pulmonary Multidrug resistant Antitubercular Agents OPC 67683
Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Start date: 2008-05-08; Completion date: 2010-06-11
Enrollment: 481 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a clinical trial to evaluate the safety and efficacy of OPC-67683 in the treatment of multidrug resistant tuberculosis (MDR TB) for 56 days. In addition to an optimized background regimen (OBR), participants will be randomized to receive:

* 100 mg OPC-67683 twice daily (BID)
* 200 mg OPC-67683 BID
* Placebo BID

After 56 days participants will complete their optimized background regimen (OBR).

Detailed description:
This is a multi center, randomized, double-blinded, stratified, placebo-controlled clinical trial in three parallel groups. Participants will be randomized to one of the following three treatment groups:

* OBR plus 100 mg OPC-67683 BID
* OBR plus 200 mg OPC-67683 BID
* OBR plus placebo BID

The three treatment groups will comprise approximately 140 participants each (male or female). The trial will consist of the following periods:

* Pre-treatment Period (Visits 1 to 3 \[Day -9 to Day -1\])
* Treatment Period (Visits 4 to 59 \[Days 1 to 56\])
* Post-treatment Period (Visits 60 to 64 \[Days 57 to 84\])

Enrolled participants (those accepted into the screening period of the trial who signed an informed consent form) will be stratified at randomization by extent of pulmonary TB; an equal number of participants with and without cavities visible in the lung fields on baseline chest radiograph will be allocated to each treatment group. A total of approximately 430 male or female participants aged 18 to 64 years, inclusive, with pulmonary, sputum culture-positive MDR TB (TB caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampicin) or with sputum smears positive for acid fast bacilli (AFB) and a positive rapid test for rifampicin resistance on direct sputum within 60 days prior to the expected date of enrollment. Participants with positive AFB smears and a positive rapid rifampicin resistance test will be enrolled as presumptively culture positive and withdrawn as ineligible if they are confirmed to not have sputum culture positive MDR TB.

Arms: arm 1: Participants received delamanid 100 milligrams (mg) (two 50 mg tablets), orally, BID with two matching placebo tablets plus optimized background regimen (OBR) for 56 consecutive days (from Day 1 to Day 56).

Participants were administered OBR as directed by the given investigator based on World Health Organization (WHO) guidelines and clinical judgment, in conjunction with national TB program guidelines in each country. arm 2: Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).

Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country. arm 3: Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56).

Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.
Interventions: intervention 1: Delamanid intervention 2: Optimized Background Regimen (OBR) intervention 3: Placebo
Intervention descriptions: intervention 1: Delamanid was administered orally twice daily as 50-mg tablets under fed conditions in the morning and evening. intervention 2: Selection and administration of the treatment medications (i.e., OBRs) was based on World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country.

Study Investigator could change OBR for a participant based on participant's tolerability and drug susceptibility testing (DST) results. intervention 3: Placebo tablets matching 50-mg tablets of delamanid

Protocol documents: