Clinical Trial: A Placebo-controlled, Phase 2 Trial to Evaluate OPC 67683 in Patients With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi Center, Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Doses of OPC 67683 in Patients With Pulmonary Sputum Cultur

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).patients will receive will be randomized to:

  • 100 mg OPC-67683 BID
  • 200 mg OPC-67683 BID
  • placebo BID After 56 days subjects will complete their OBR.

Detailed Summary:

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

  • Optimized Background Regimen (OBR) plus 100 mg OPC-67683 twice daily
  • OBR plus 200 mg OPC-67683 twice daily
  • OBR plus placebo twice daily

The three treatment groups will comprise approximately 140 patients 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 patients (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 patients with and without cavities visible in the lung fields on baseline chest radiograph will be allocated to each treatment group. A total of 430 male or female patients 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. Patients 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AFB smears and a positive rapid rifampicin resistance test will be enrolled as presumptively culture positive and withdrawn as ineligible if they are confirmed to not have sputum culture positive MDR TB. Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

    Current Primary Outcome:

    • The primary efficacy endpoint is the proportion of patients who achieve sputum mycobacterial culture conversion within 56 full days or less of treatment. [ Time Frame: 84 days ]
    • Reported adverse events, physical examination, vital signs (blood pressure, heart rate, body temperature and weight), standard 12-lead ECG, clinical laboratory assessment results (hematology, chemistry, urinalysis). [ Time Frame: 84 days ]


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • PK: For OPC-67683, tmax, Cmax, AUC0-24h , ratios of accumulation for Cmax and AUC0-24h, Day 14, 28 or 56/Day 1. For the metabolites, tmax, Cmax, AUC0-24h , ratios of accumulation for Cmax and AUC0-24h , Day 14, 28 or 56/Day 1] [ Time Frame: 84 days ]
    • Efficacy: Change from baseline in time to culture positivity using the MGIT® system. AUC of change from baseline in time to culture positivity in the MGIT® system [ Time Frame: 84 days ]
    • Efficacy: Proportion of patients with sputum mycobacterial culture negative for growth at Day 57 (1=negative, 0=positive) using the MGIT® culture system without regard to subsequent culture results. [ Time Frame: 84 days ]
    • Efficacy: Proportion of patients achieving sputum culture conversion from positive growth at baseline (pre-dose) to negative growth on solid mycobacterial culture media within 56 full days of treatment out of all evaluable patients. [ Time Frame: 84 days ]
    • Efficacy: Proportion of patients with sputum mycobacterial culture positive for growth at baseline who have negative growth at Day 57 (1=negative, 0=positive) using solid culture media without regard to subsequent culture results. [ Time Frame: 84 days ]
    • Efficacy: Dose-response in sputum culture conversion rates for results from the MGIT system. Dose-response in sputum culture conversion rates for results from solid culture media. [ Time Frame: 84 days ]


    Original Secondary Outcome: Same as current

    Information By: Otsuka Pharmaceutical Development & Commercialization, Inc.

    Dates:
    Date Received: May 20, 2008
    Date Started: April 2008
    Date Completion:
    Last Updated: August 13, 2015
    Last Verified: August 2015