Clinical trial NCT04044001: BTZ-043 - Multiple Ascending Dose (MAD) to Evaluate Safety, Tolerability and Early Bactericidal Activity (EBA)
Official title: A Prospective Phase Ib/IIa, Active-controlled, Randomized, Open-label Study to Evaluate the Safety, Tolerability, Extended Early Bactericidal Activity and Pharmacokinetics of Multiple Oral Doses of BTZ-043 Tablets in Subjects With Newly Diagnosed, Uncomplicated, Smear-positive, Drug-susceptible Pulmonary Tuberculosis
Conditions: Pulmonary Tuberculoses
Other Specified Pulmonary Tuberculosis
Summary: This is a prospective, open label, two-centre, randomized, controlled, two-stage, phase Ib/IIa study to evaluate the safety, tolerability, PK, drug-drug interaction and bactericidal activity of BTZ-043 administered orally once daily over 14 days to participants with newly diagnosed, uncomplicated, smear-positive, drug-susceptible pulmonary tuberculosis.
The primary objective is to assess the safety and tolerability of BTZ-043 given over 14 days by evaluation of adverse events during treatment and follow-up period in patients with newly diagnosed, uncomplicated, smear-positive, drug-susceptible pulmonary tuberculosis.
Interventions:
description: BTZ-043 (250mg per tablet)
name: BTZ-043
type: Drug
description: Rifafour e-275® (150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, 275 mg ethambutol per tablet)
name: Rifafour e-275®
other_name: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (HRZE)
type: Drug
description: A probe drug cocktail will be given to randomly selected patients after inclusion on Day 1 and on Day 14 once orally. The probe drug cocktail consists of<br/>* Caffeine: 1 tablet à 150mg<br/>* Tolbutamide: 1/4 tablet à 500mg<br/>* Dextromethorphan: 10 ml syrup à 15mg/5ml<br/>* Midazolam:2 ml solution à 5mg/5ml<br/>* Digoxin: 2 tablets à 0.25mg
name: Probe Drug Cocktail
type: Drug
description: 1 tablet à 50mg Dolutegravir will be given to randomly selected patients after inclusion on Day 1 and on Day 14 once orally.
name: Dolutegravir 50mg Tab
other_name: Tivicay®
type: Drug
Study arms:
design_group_description: Patients will receive 1 tablet of BTZ-043 orally once daily, containing 250mg BTZ-043 from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 1 (BTZ 250)
design_group_type: Experimental
design_group_description: Patients will receive 2 tablets of BTZ-043 orally once daily, each containing 250mg BTZ-043 (500 mg in total) from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 2 (BTZ 500)
design_group_type: Experimental
design_group_description: Patients will receive 3 tablets of BTZ-043 orally once daily, each containing 250mg BTZ-043 (750 mg in total) from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 3 (BTZ 750)
design_group_type: Experimental
design_group_description: Patients will receive 4 tablets of BTZ-043 orally once daily, each containing 250mg BTZ-043 (1000 mg in total) from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 4 (BTZ 1000)
design_group_type: Experimental
design_group_description: Patients will receive 5 tablets of BTZ-043 orally once daily, each containing 250mg BTZ-043 (1250 mg in total) from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 5 (BTZ 1250)
design_group_type: Experimental
design_group_description: Patients will receive 6 tablets of BTZ-043 orally once daily, each containing 250mg BTZ-043 (1500 mg in total) from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 6 (BTZ 1500)
design_group_type: Experimental
design_group_description: Patients will receive 7 tablets of BTZ-043 orally once daily, each containing 250mg BTZ-043 (1750 mg in total) from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 7 (BTZ 1750)
design_group_type: Experimental
design_group_description: Patients will receive 8 tablets of BTZ-043 orally once daily, each containing 250mg BTZ-043 (2000 total) from Day 1 through to Day 14
design_group_title: Stage 1 - Cohort 8 (BTZ 2000)
design_group_type: Experimental
design_group_description: Patients will receive a higher dose of BTZ-043, that has proven to be safe in stage 1 orally once daily from Day 1 through to Day 14. The dose of BTZ-043 will be determined after review of safety data from stage 1.
design_group_title: Stage 2 - Arm 1 (BTZ high)
design_group_type: Experimental
design_group_description: Patients will receive a medium dose of BTZ-043, that has proven to be safe in stage 1 orally once daily from Day 1 through to Day 14. The dose of BTZ-043 will be determined after review of safety data from stage 1.
design_group_title: Stage 2 - Arm 2 (BTZ medium)
design_group_type: Experimental
design_group_description: Patients will receive a lower dose of BTZ-043, that has proven to be safe in stage 1 orally once daily from Day 1 through to Day 14. The dose of BTZ-043 will be determined after review of safety data from stage 1.
design_group_title: Stage 2 - Arm 3 (BTZ low)
design_group_type: Experimental
design_group_description: Patients will receive a standard dose of Rifafour e-275® orally once daily according to body weight from Day 1 through to Day 14. Each tablet of Rifafour e-275® contains 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide and 275mg ethambutol.<br/>The daily doses will be given to fasting patients, in accordance with South African Guidelines for treatment of TB. The total number of tablets will be based on the body weight at screening:<br/>* participants weighing 38 - 54 kg: 3 tablets<br/>* participants weighing 55 - 70 kg: 4 tablets<br/>* participants weighing >70 kg: 5 tablets
design_group_title: Stage 2 - Arm 4 (control)
design_group_type: Active Comparator
Sponsor: Ludwig-Maximilians-Universität München
Collaborators: Radboud University Medical Center
German Federal Ministry Of Education And Research
Drug name mappings:
name: 多替拉韦钠
lang: CN
name: Dolutegravir Sodium
lang: EN
name: ドルテグラビルナトリウム
lang: JP
name: BTZ-043
lang: EN