A Phase 3 Study Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Drug Resistant Pulmonary Tuberculosis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02333799|
Recruitment Status : Active, not recruiting
First Posted : January 7, 2015
Last Update Posted : May 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Tuberculosis||Drug: Bedaquiline Drug: PA-824 Drug: Linezolid||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||109 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3 Open-label Trial Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Pulmonary Infection of Either Extensively Drug-resistant Tuberculosis (XDR-TB) or Treatment Intolerant / Non-responsive Multi-drug Resistant Tuberculosis (MDR-TB).|
|Study Start Date :||March 2015|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||October 2021|
Experimental: Bedaquiline + PA-824 + Linezolid
bedaquiline 400 mg once daily for 2 weeks then 200mg 3 times per week plus PA-824 200mg once daily plus linezolid 1200mg once daily .
Scored 600mg tablets
- Incidence of bacteriologic failure or relapse or clinical failure through follow up until 6 months after the end of treatment. [ Time Frame: Treatment Period: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, 30, 34, 39 Follow Up: Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 ]
Bacteriologic failure: During the treatment period, failure to attain culture conversion to negative.
Bacteriologic relapse: During the follow-up period, failure to maintain culture conversion to negative status in culture, with culture conversion to positive status with a Mycobacterium tuberculosis (M.tb.) strain that is genetically identical to the infecting strain at baseline.
Clinical failure: A change from protocol-specified TB treatment due to treatment failure, retreatment for TB during follow up, or TB-related death.
Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart.
Subjects who are documented at a visit as unable to produce sputum and who are clinically considered to be responding well to treatment will be considered to be culture negative at that visit.
- Time to sputum culture conversion to negative status through the treatment period. [ Time Frame: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 ]
- Proportion of subjects with sputum culture conversion to negative status at 4, 6, 8, 12, 16 and 26 or 39 weeks. [ Time Frame: Week 4, 6, 8, 12, 16, 26, 39 ]
- Incidence of Treatment Emergent Adverse Events (TEAEs) presented by incidence, and seriousness, leading to TB related or non-TB related death. [ Time Frame: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, 30, 34, 39, Follow-up Month 3, 6, 9, 12, 15, 18, 21, 24 ]
- All Subjects- Pre-dose sampling at weeks 2, 8 and 16 to measure Ctrough levels of bedaquiline, bedaquiline metabolite M2, Linezolid and PA-824. [ Time Frame: Weeks 2, 8 and 16 ]
- Time to sputum culture positivity [ Time Frame: Treatment Period: Day 1, Week 1, 2, 4, 6, 8, 12, 16, 20, 26, 30, 34, 39 Follow Up: Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 ]If liquid culture in the MGIT platform is used, the rate of change in time to sputum culture positivity (TTP) over time in the Mycobacterial Growth Indicator Tube (MGIT) system in sputum, represented by the model-fitted log(TTP) results as calculated by the regression of the observed log(TTP) results over time.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02333799
|Task Applied Science - Brooklyn Chest Hospital|
|Ysterplaat, Cape Town, South Africa, 7405|
|King DinuZulu Hospital Complex|
|Sydenham, Durban, South Africa, 4001|
|Sizwe Tropical Disease Hospital|
|Sandringham, Johannesburg, South Africa, 2131|
|THINK: Tuberculosis & HIV Investigative Network of KwaZulu-Natal (Durban)|
|Pietermaritzburg, Kwazulu-Natal, South Africa, 3200|
|Principal Investigator:||Dan Everitt, MD||Global Alliance for TB Drug Development|
|Principal Investigator:||Francesca Conradie, MD||CHRU Themba Lethu Clinic - Helen Joseph Hospital|