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Early Bactericidal Activity of TBA-7371 in Pulmonary Tuberculosis

Sponsor
Bill & Melinda Gates Medical Research Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT04176250
Collaborator
(none)
90
Enrollment
4
Locations
6
Arms
30.5
Anticipated Duration (Months)
22.5
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety, early bactericidal activity (EBA) and pharmacokinetics of TBA-7371 in adult participants with rifampicin-sensitive tuberculosis and select dose regimen(s) for future studies.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2a, Dose Escalation, Controlled, Randomized Study to Evaluate Safety, Early Bactericidal Activity (EBA) and Pharmacokinetics of TBA-7371 in Adult Patients With Rifampicin-sensitive Pulmonary Tuberculosis
Actual Study Start Date :
Jan 16, 2020
Anticipated Primary Completion Date :
Aug 1, 2022
Anticipated Study Completion Date :
Aug 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: TBA-7371 100 mg QD

Drug: TBA-7371
Participants will receive TBA-7371 oral suspension 100 milligram (mg) once daily (QD) for 14 days.
Experimental: TBA-7371 100 mg BID

Drug: TBA-7371
Participants will receive TBA-7371 oral suspension 100 mg twice daily (BID) for 14 days.
Experimental: TBA-7371 200 mg QD

Drug: TBA-7371
Participants will receive TBA-7371 oral suspension 200 mg QD for 14 days.
Experimental: TBA-7371 100 mg TID

Drug: TBA-7371
Participants will receive TBA-7371 oral suspension 100 mg three times daily (TID) for 14 days.
Experimental: TBA-7371 400 mg QD

Drug: TBA-7371
Participants will receive TBA-7371 oral suspension 400 mg QD for 14 days.
Active Comparator: HRZE

Drug: HRZE
Participants will receive Isoniazid [H] / rifampicin [R] / pyrazinamide [Z] / ethambutol [E] (HRZE), a fixed dose combination (H: 75 mg / R: 150 mg / Z: 400 mg / E: 275 mg) tablet QD for 14 days.
Other Names:
  • Rifafour® e-275

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Slope of Average Change per Day, From Day 0 to Day 14 [BAcfu (0-14)] of the Log Colony Forming Units (CFU) Counts [Day 0 (screening) to Day 14]

    2. Number of Participants who Experienced One or More Severe (≥ grade 3) and/or Serious Adverse Events (SAEs) [Day 1 through Day 15]

    Secondary Outcome Measures

    1. Slope of Average Change per Day, From Day 0 to Day 2 [BAcfu (0-2)] and From Day 2 to Day 14 [BAcfu (2-14)] of the Log CFU Counts [Day 0 (Screening) to Day 2 and Day 2 to Day 14]

    2. Slope of the Time to Sputum Culture Positivity (TPP) in the Mycobacteria Growth Indicator Tube (MGIT) System From Day 0 to Day 14 [BAttp (0-14)], From Day 0 to Day 2 [BAttp (0-2)], and From Day 2 to Day 14 [BAttp (2-14)] [Day 0 (Screening) to Day 14, Day 0 (Screening) to Day 2 and Day 2 to Day 14]

    3. Slope of the Log Concentration of Sputum LipoArabinoMannan (LAM) From Day 0 to day 14 [BAlam (0-14)], From Day 0 to Day 2 [BAlam (0-2)], and From Day 2 to Day 14 [BAlam (2-14)] [Day 0 (Screening) to Day 14, Day 0 (Screening) to Day 2 and Day 2 to Day 14]

    4. Number of Participants With Adverse Events (AEs) and Frequency of AEs [Day 1 through Day 15]

    5. Frequency of Participants With Any New Eye Symptom in One or Both Eyes [Day 1 through day 15]

    6. Mean and Frequency Distribution of Duration of Each Eye Symptom [Day 1 through day 15]

    7. Mean and Frequency Distribution of Percentage of Days With Any Eye Symptom and Each of the Eye Symptoms [Day 1 through day 15]

    8. Mean Change in Visual Acuity Score From Screening to Lowest Score [Day 1 through day 15]

    9. Median Change in Visual Acuity Score From Screening to Lowest Score [Day 1 through day 15]

    10. Mean Changes in Color Vision Score From Screening to Lowest Score [Day 1 through day 15]

    11. Median Changes in Color Vision Score From Screening to Lowest Score [Day 1 through day 15]

    12. Mean and Frequency Distribution of Changes in Heart Rate (HR) [Day 1 through day 15]

    13. Mean and Frequency Distribution of Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Day 1 through day 15]

    14. Number of Participants With ≥ 25 % Increase in HR, Decrease in SBP, Decrease in DBP [Day 1 through day 15]

    15. Mean and Frequency Distribution of Percentage of Days With ≥ 25% Increase in HR, Decrease in SBP, Decrease in DBP [Day 1 through day 15]

    16. Mean/median Change in PR, RR, QRS, QT, QTcF Values From Baseline ECG [Day 0 (screening) Through Day 15]

    17. Mean Change in HR [Day 1 to days 4, 7, 10, 14 and 15]

    18. Mean Change in SBP and DBP [Day 1 to days 4, 7, 10, 14 and 15]

    19. Change in Number of Participants With Eye Symptoms (All, Severe, Serious) [Day 1 to days 4, 7, 10, 14 and 15]

    20. Change in Mean Visual Acuity Score [Day 1 to days 4, 7, 10, 14 and 15]

    21. Change in Mean Color Vision Score [Day 1 to days 4, 7, 10, 14 and 15]

    22. Mean Change in HR [Day 0 (Screening) to days 28 and 42; and from day 14 to days 28 and 42]

    23. Mean Change in SBP and DBP [Day 0 (Screening) to days 28 and 42; and from day 14 to days 28 and 42]

    24. Change in Number of Participants with Eye Symptoms (All, Severe, Serious) [Day 0 (Screening) to days 28 and 42; and from days 1-15 (combined) to days 28-42 (combined)]

    25. Change in Mean Visual Acuity Score [Day 0 (Screening) to days 28 and 42; and from days 1-15 (combined) to days 28-42 (combined)]

    26. Change in Mean Color Vision Score [Day 0 (Screening) to days 28 and 42; and from days 1-15 (combined) to days 28-42 (combined)]

    27. Mean Concentration of Clinical Safety Haematology Parameter: Red Blood Cells [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    28. Median Concentration of Clinical Safety Haematology Parameter: Red Blood Cells [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    29. Mean Change From Screening in Clinical Safety Haematology Parameter: Red Blood Cells [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    30. Median Change From Screening in Clinical Safety Haematology Parameter: Red Blood Cells [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    31. Mean Concentration of Clinical Safety Haematology Parameter: Haemoglobin [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    32. Median Concentration of Clinical Safety Haematology Parameter: Haemoglobin [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    33. Mean Change From Screening in Clinical Safety Haematology Parameter: Haemoglobin [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    34. Median Change From Screening in Clinical Safety Haematology Parameter: Haemoglobin [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    35. Mean Concentration of Clinical Safety Haematology Parameter: Platelets [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    36. Median Concentration of Clinical Safety Haematology Parameter: Platelets [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    37. Mean Change From Screening in Clinical Safety Haematology Parameter: Platelets [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    38. Median Change From Screening in Clinical Safety Haematology Parameter: Platelets [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    39. Mean Concentration of Clinical Safety Haematology Parameter: White Blood Cells [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    40. Median Concentration of Clinical Safety Haematology Parameter: White Blood Cells [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    41. Mean Change From Screening in Clinical Safety Haematology Parameter: White Blood Cells [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    42. Median Change From Screening in Clinical Safety Haematology Parameter: White Blood Cells [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    43. Mean Levels of Clinical Safety Haematology Parameter: Neutrophils [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    44. Median Levels of Clinical Safety Haematology Parameter: Neutrophils [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    45. Mean Change From Screening in Clinical Safety Haematology Parameter: Neutrophils [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    46. Median Change From Screening in Clinical Safety Haematology Parameter: Neutrophils [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    47. Mean Levels of Clinical Safety Haematology Parameter: Lymphocytes [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    48. Median Levels of Clinical Safety Haematology Parameter: Lymphocytes [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    49. Mean Change From Screening in Clinical Safety Haematology Parameter: Lymphocytes [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    50. Median Change From Screening in Clinical Safety Haematology Parameter: Lymphocytes [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    51. Mean Levels of Clinical Safety Haematology Parameter: Monocytes [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    52. Median Levels of Clinical Safety Haematology Parameter: Monocytes [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    53. Mean Change From Screening in Clinical Safety Haematology Parameter: Monocytes [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    54. Median Change From Screening in Clinical Safety Haematology Parameter: Monocytes [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    55. Mean Levels of Clinical Safety Haematology Parameter: Eosinophils [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    56. Median Levels of Clinical Safety Haematology Parameter: Eosinophils [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    57. Mean Change From Screening in Clinical Safety Haematology Parameter: Eosinophils [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    58. Median Change From Screening in Clinical Safety Haematology Parameter: Eosinophils [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    59. Mean Levels of Clinical Safety Haematology Parameter: Basophils [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    60. Median Levels of Clinical Safety Haematology Parameter: Basophils [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    61. Mean Change From Screening in Clinical Safety Haematology Parameter: Basophils [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    62. Median Change From Screening in Clinical Safety Haematology Parameter: Basophils [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    63. Mean Concentration of Clinical Safety Serum Chemistry Parameter: Alanine Aminotransferase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    64. Median Concentration of Clinical Safety Serum Chemistry Parameter: Alanine Aminotransferase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    65. Mean Change From Screening in Clinical Safety Serum Chemistry Parameter: Alanine Aminotransferase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    66. Median Change From Screening in Clinical Safety Serum Chemistry Parameter: Alanine Aminotransferase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    67. Mean Concentration of Clinical Safety Serum Chemistry Parameter: Aspartate Aminotransferase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    68. Median Concentration of Clinical Safety Serum Chemistry Parameter: Aspartate Aminotransferase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    69. Mean Change From Screening in Clinical Safety Serum Chemistry Parameter: Aspartate Aminotransferase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    70. Median Change From Screening in Clinical Safety Serum Chemistry Parameter: Aspartate Aminotransferase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    71. Mean Concentration of Clinical Safety Serum Chemistry Parameter: Alkaline Phosphatase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    72. Median Concentration of Clinical Safety Serum Chemistry Parameter: Alkaline Phosphatase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    73. Mean Change From Screening in Clinical Safety Serum Chemistry Parameter: Alkaline Phosphatase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    74. Median Change From Screening in Clinical Safety Serum Chemistry Parameter: Alkaline Phosphatase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    75. Mean Concentration of Clinical Safety Serum Chemistry Parameter: Total Bilirubin [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    76. Median Concentration of Clinical Safety Serum Chemistry Parameter: Total Bilirubin [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    77. Mean Change From Screening in Clinical Safety Serum Chemistry Parameter: Total Bilirubin [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    78. Median Change From Screening in Clinical Safety Serum Chemistry Parameter: Total Bilirubin [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    79. Mean Concentration of Clinical Safety Serum Chemistry Parameter: Creatinine [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    80. Median Concentration of Clinical Safety Serum Chemistry Parameter: Creatinine [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    81. Mean Change From Screening in Clinical Safety Serum Chemistry Parameter: Creatinine [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    82. Median Change From Screening in Clinical Safety Serum Chemistry Parameter: Creatinine [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    83. Mean Concentration of Clinical Safety Serum Chemistry Parameter: Blood Urea Nitrogen [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    84. Median Concentration of Clinical Safety Serum Chemistry Parameter: Blood Urea Nitrogen [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    85. Mean Change From Screening in Clinical Safety Serum Chemistry Parameter: Blood Urea Nitrogen [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    86. Median Change From Screening in Clinical Safety Serum Chemistry Parameter: Blood Urea Nitrogen [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    87. Mean Concentration of Clinical Safety Serum Coagulation Parameter: Prothrombin Time [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    88. Median Concentration of Clinical Safety Serum Coagulation Parameter: Prothrombin Time [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    89. Mean Change From Screening in Clinical Safety Serum Coagulation Parameter: Prothrombin Time [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    90. Median Change From Screening in Clinical Safety Serum Coagulation Parameter: Prothrombin Time [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    91. Mean Concentration of Clinical Safety Serum Coagulation Parameter: Partial Thromboplastin Time [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    92. Median Concentration of Clinical Safety Serum Coagulation Parameter: Partial Thromboplastin Time [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    93. Mean Change From Screening in Clinical Safety Serum Coagulation Parameter: Partial Thromboplastin Time [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    94. Median Change From Screening in Clinical Safety Serum Coagulation Parameter: Partial Thromboplastin Time [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    95. Mean Concentration of Clinical Safety Serum Coagulation Parameter: International Normalized Ratio [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    96. Median Concentration of Clinical Safety Serum Coagulation Parameter: International Normalized Ratio [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    97. Mean Change From Screening in Clinical Safety Serum Coagulation Parameter: International Normalized Ratio [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    98. Median Change From Screening in Clinical Safety Serum Coagulation Parameter: International Normalized Ratio [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    99. Mean Concentration of Clinical Safety Urinalysis Parameter: Specific Gravity [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    100. Median Concentration of Clinical Safety Urinalysis Parameter: Specific Gravity [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    101. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Specific Gravity [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    102. Median Change From Screening in Clinical Safety Urinalysis Parameter: Specific Gravity [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    103. Mean Concentration of Clinical Safety Urinalysis Parameter: Potential of Hydrogen (pH) [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    104. Median Concentration of Clinical Safety Urinalysis Parameter: pH [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    105. Mean Change From Screening in Clinical Safety Urinalysis Parameter: pH [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    106. Median Change From Screening in Clinical Safety Urinalysis Parameter: pH [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    107. Mean Concentration of Clinical Safety Urinalysis Parameter: Glucose [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    108. Median Concentration of Clinical Safety Urinalysis Parameter: Glucose [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    109. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Glucose [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    110. Median Change From Screening in Clinical Safety Urinalysis Parameter: Glucose [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    111. Mean Concentration of Clinical Safety Urinalysis Parameter: Protein [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    112. Median Concentration of Clinical Safety Urinalysis Parameter: Protein [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    113. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Protein [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    114. Median Change From Screening in Clinical Safety Urinalysis Parameter: Protein [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    115. Mean Concentration of Clinical Safety Urinalysis Parameter: Blood [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    116. Median Concentration of Clinical Safety Urinalysis Parameter: Blood [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    117. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Blood [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    118. Median Change From Screening in Clinical Safety Urinalysis Parameter: Blood [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    119. Mean Concentration of Clinical Safety Urinalysis Parameter: Ketones [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    120. Median Concentration of Clinical Safety Urinalysis Parameter: Ketones [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    121. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Ketones [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    122. Median Change From Screening in Clinical Safety Urinalysis Parameter: Ketones [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    123. Mean Concentration of Clinical Safety Urinalysis Parameter: Bilirubin [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    124. Median Concentration of Clinical Safety Urinalysis Parameter: Bilirubin [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    125. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Bilirubin [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    126. Median Change From Screening in Clinical Safety Urinalysis Parameter: Bilirubin [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    127. Mean Concentration of Clinical Safety Urinalysis Parameter: Urobilinogen [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    128. Median Concentration of Clinical Safety Urinalysis Parameter: Urobilinogen [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    129. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Urobilinogen [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    130. Median Change From Screening in Clinical Safety Urinalysis Parameter: Urobilinogen [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    131. Mean Concentration of Clinical Safety Urinalysis Parameter: Nitrite [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    132. Median Concentration of Clinical Safety Urinalysis Parameter: Nitrite [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    133. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Nitrite [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    134. Median Change From Screening in Clinical Safety Urinalysis Parameter: Nitrite [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    135. Mean Concentration of Clinical Safety Urinalysis Parameter: Leukocyte Esterase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    136. Median Concentration of Clinical Safety Urinalysis Parameter: Leukocyte Esterase [Day 0 (Screening), Day 3, Day 7, Day 14 and Day 42]

    137. Mean Change From Screening in Clinical Safety Urinalysis Parameter: Leukocyte Esterase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    138. Median Change From Screening in Clinical Safety Urinalysis Parameter: Leukocyte Esterase [Day 0 (Screening) to Day 3, Day 7, Day 14 and Day 42]

    139. TBA7371 Pharmacokinetic Parameter (PK): Maximum Plasma Concentration (Cmax) [Days 1, 2, 4, 7 and 14]

    140. TBA7371 PK Parameter: Time to Maximum Plasma Concentration (Tmax) [Days 1, 2, 4, 7 and 14]

    141. TBA7371 PK Parameter: Last Measurable Concentration (Clast) [Days 1, 2, 4, 7 and 14]

    142. TBA7371 PK Parameter: Time to Last Measurable Concentration (Tlast) [Days 1, 2, 4, 7 and 14]

    143. TBA7371 PK Parameter: Area Under the Plasma Concentration-Time Curve (AUC) Extrapolated to Infinity (AUCinf) [Days 1, 2, 4, 7 and 14]

    144. TBA7371 PK Parameter: Area Under the Plasma Concentration-Time Curve from 0 up to the Last Measurable Concentration (AUClast) [Days 1, 2, 4, 7 and 14]

    145. TBA7371 PK Parameter: AUC to the End of the Dosing Period (AUCtau) [Days 1, 2, 4, 7 and 14]

    146. TBA7371 PK Parameter: Half-Life [Days 1, 2, 4, 7 and 14]

    147. PK Parameter: Accumulation Ratios [Days 1, 2, 4, 7 and 14]

    148. Expected Concentration Associated With 90% of the Maximal TBA-7371 Early Bactericidal Activity (EBA) Effect (EC90) [Day 0 (Screening) to Day 14]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Participants between 18 to 60 years of age inclusive at the time of signing the informed consent.

    • Body weight within 40 and 100 kilogram (inclusive).

    • Untreated, rifampicin-sensitive pulmonary tuberculosis, as defined by all of the following:

    1. isoniazid urine screen negativity

    2. sputum smear positivity on direct microscopy for acid-fast bacilli, defined as at least 1+ on the International Unit Against Tuberculosis and Lung Disease/ World Health Organization scale

    3. chest X-rays which in the opinion of the investigator is consistent with tuberculosis (TB).

    4. Mycobacterium tuberculosis (Mtb) positivity on molecular test (GeneXpert®)

    5. rifampicin sensitivity on molecular test (GeneXpert®).

    • Participants must be able to produce at least 10 milliliter of sputum during the overnight sputum collection (day -7 to -3 or day -2 of the Screening Phase).

    • Female and male participants should be of non-childbearing potential or using an effective method of birth control.

    • Non-childbearing potential is defined as follows:

    1. participant is not heterosexually active or practices sexual abstinence, OR

    2. female participant or sexual partner has undergone bilateral oophorectomy, bilateral tubal ligation and/or hysterectomy, OR

    3. female participant or sexual partner has been postmenopausal with a history of no menses for at least 12 consecutive months, OR

    4. male participant or sexual partner has undergone vasectomy or bilateral orchidectomy at least three months prior to screening, OR

    5. male participant with pregnant sexual partner (for duration of the study) who does not have any other sexual partners.

    • An effective method of birth control is defined as follows:

    1. double barrier method, which can include any 2 of the following: a male condom, diaphragm, cervical cap, or female condom (male and female condoms should not be used together), OR

    2. barrier method (one of the above) combined with hormone-based contraceptives or an intra-uterine device for the female participant or partner, AND

    3. participant willing to continue practicing one of the above-mentioned birth control methods throughout 14-day Study Treatment Phase and for 4 weeks after the last dose of study medication or discontinuation from study medication in case of early withdrawal.

    • Participants must be capable of giving signed informed consent, which includes agreeing to compliance with the requirements and restrictions listed in the informed consent form and the protocol.
    Exclusion Criteria:

    • Need for immediate effective anti-TB treatment as judged by the investigator.

    • Evidence and/or history of extra-thoracic TB (e.g. miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis, ocular TB), as judged by the investigator.

    • Evidence and/or history in the last 5 years of one or any combination of the following:

    1. uveitis;

    2. color vision deficiency;

    3. amblyopia;

    4. visual acuity worse than 20/25 after correction in either eye;

    5. any known eye disease or prior eye surgery;

    6. any systemic condition with ocular manifestations (i.e. Marfan, syphilis, diabetes, Beçhet, Vogt-Koyanagi-Harada, Lyme, or chronic inflammatory condition such as sarcoidosis, rheumatoid arthritis, psoriatic arthritis)

    • Evidence and/or history in the last 5 years of clinically significant medical condition(s) as judged by the investigator, including malignancies and unstable or uncontrolled hypertension.

    • Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol.

    • For Human Immunodeficiency Virus infected participants:

    1. CD4+ count <350 cells/microliter, OR

    2. Acquired Immune Deficiency Syndrome-defining opportunistic infection or malignancies (except pulmonary TB).

    • Seated systolic/diastolic blood pressure assessed as vital sign [i.e. not from electrocardiogram (ECG)] is less than 95/40 millimeters of Mercury (mmHg) or greater than 145/95 mmHg at screening. Out-of-range blood pressure may be repeated twice with at least 5 minutes intervening.

    • Seated heart rate assessed as vital sign (i.e. not from ECG) is lower than 40 beats per minute (bpm) or higher than 110 bpm at screening. Out-of-range heart rate may be repeated twice with at least 5 minutes intervening.

    • A clinically significant ECG abnormality at screening. NOTE: The following can be considered not clinically significant:

    1. mild first-degree atrio-ventricular block (P-R interval <0.23 seconds);

    2. right or left axis deviation;

    3. incomplete right bundle branch block;

    4. isolated left anterior fascicular block (left anterior hemiblock) in young athletic participants.

    • A list of commonly used prohibited medications with the features described below are prohibited:

    • Use of medications active against Mtb within 3 months prior to the first dose of study drug.

    • Use of systemic immunosuppressive medications within 14 days prior to the first dose of study drug.

    • Use of strong inhibitors or strong inducers of cytochrome P450 (CYP) enzymes within 14 days prior to the first dose of study drug.

    • Use of inhibitors of phosphodiesterase (PDE) enzymes within 14 days prior to the first dose of study drug.

    • Use of medications known to affect the eye within 3 months prior to the first dose of study drug.

    • For Human Immunodeficiency Virus positive participants, use of medications listed in the protocol within 3 months prior to the first dose of study drug.

    • Participation in other clinical study(-ies) with investigational agent(s) within 6 months prior to trial start.

    • The following laboratory values from blood collected during the Screening Phase, which represent Grade 2 or higher abnormalities per Division of Acquired Immune Deficiency

    Syndrome (DAIDS) Toxicity Table Version 2.1, will be cause for exclusion:

    • Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase ≥ 2.5x upper limit of normal (ULN) for local laboratory values

    • Total bilirubin ≥ 1.6x ULN

    • Creatinine ≥ 1.3x ULN

    • Hemoglobin < 10 grams per deciliter (g/dL) [male] or 9.5 g/dL [female]

    • White Blood Cells < 2,000 /cubic millimeter (mm3)

    • Platelets ≤ 100,000 /mm3

    • International normalized ratio of prothrombin time (INR) ≥ 1.5x ULN

    • Partial thromboplastin time (PTT) ≥ 1.66 ULN

    • Prothrombin time (PT) ≥ 1.25x ULN

    Grade 2 or higher abnormalities in other laboratory parameters from blood or urine Grade 1 abnormalities, or abnormalities from laboratory parameters not included in the DAIDS Toxicity Table Version 2.1, may lead to exclusion if the investigator considers them clinically significant.

    • History of allergy or hypersensitivity to any of the study drugs or related substances.

    • Positive urine drug screening for cocaine AND/OR amphetamines AND/OR opiates AND/OR methamphetamines. Note: screening will also be conducted for cannabinoids and results documented in the case report form; however, a positive test for cannabinoids is not an exclusion criterion.

    • Female participants currently pregnant or lactating/nursing; OR having positive serum pregnancy test during the Screening Phase OR planning a pregnancy within the 1 month after first dose of study drug.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Investigational Site Bellville Cape Town South Africa 7530
    2 Investigational Site Mowbray Cape Town South Africa 7700
    3 Investigational Site Pretoria Gauteng South Africa 0087
    4 Investigational Site Jouberton North West Province South Africa 2574

    Sponsors and Collaborators

    • Bill & Melinda Gates Medical Research Institute

    Investigators

    • Study Director: Gates MRI, Bill & Melinda Gates Medical Research Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bill & Melinda Gates Medical Research Institute
    ClinicalTrials.gov Identifier:
    NCT04176250
    Other Study ID Numbers:
    • Gates MRI-TBD03-201
    First Posted:
    Nov 25, 2019
    Last Update Posted:
    Jun 8, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bill & Melinda Gates Medical Research Institute
    Rifampicin-sensitive pulmonary tuberculosis
    TBA-7371
    Pulmonary tuberculosis
    Additional relevant MeSH terms:
    Tuberculosis
    Tuberculosis, Pulmonary

    Study Results

    No Results Posted as of Jun 8, 2022