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| ID | Type | Description | Link |
|---|---|---|---|
| PanACEA-DECODE-01 | Other Identifier | PanACEA |
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| Name | Class |
|---|---|
| Ludwig-Maximilians - University of Munich | OTHER |
| Radboud University Medical Center | OTHER |
| University of California, San Francisco | OTHER |
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This trial is to describe the safety, tolerability and exposure-toxicity relationship of Depazolid given over 16 weeks, in combination with standard-dose Bedaquiline, Delamanid and Moxifloxacin, compared to standard-dose Bedaquiline, Delamanid and Moxifloxacin alone
This will be an open label Phase IIb dose-finding, randomized, controlled study with a duration of 16 weeks of experimental therapy of Delpazolid(DZD) - Bedaquiline/Delamanid/ Moxifloxacin (BDM) in adult patients with newly diagnosed, smear positive, uncomplicated, drug sensitive pulmonary tuberculosis (TB) to evaluate the safety, efficacy, tolerability, pharmacokinetics and exposure/response-relationship of different doses of delpazolid in combination with bedaquiline, delamanid and moxifloxacin.
Participants will be randomized to one of five arms containing BDM standard dose with different doses of DZD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm1(D0) | Active Comparator | Participants receive the following medication for the duration of 16weeks together with food.
|
|
| Arm2(D400) | Experimental | Participants receive the following medication for the duration of 16weeks together with food.
|
|
| Arm3(D800-OD) | Experimental | Participants receive the following medication for the duration of 16weeks together with food.
|
|
| Arm4(D1200) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Delpazolid | Drug | Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety Outcome : Proportion of Patients Experiencing Adverse Event | Participants with ≥ 1 TEAE, by severity, related Adverse events: possibly, probably, or definitely related to study drugs | week0 - week52 |
| Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_AUC0-24 | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM. | Week 0 - Week 16 |
| Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_Cmax | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM. | Week 0 - Week 16 |
| Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_Cmin | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM. | Week 0 - Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy Outcome: BD MGIT960® Liquid Media Culture Results | Summary of Changes in Mycobacterial Load Over Time on Treatment as Quantified by Time to Positivity in BD MGIT960® Liquid Media - Intent to Treat Population Sputum samples were collected for BD MGIT960® Liquid Media culture at all time points during the treatment and follow-up phases, and this table shows culture results, which are reported as: Positive, Negative, Contaminated, Missing. Note: Contaminated cultures are shown as contaminated for the purpose of the overall result but are counted as missing for calculating summary statistics. The data recorded as 'Positive for MTB Complex with Contamination' are included as 'Positive' for MGIT result. However, the data from mean and median calculations for TTP (Time to positive) due to contamination. |
Not provided
Inclusion Criteria:
Provide written, informed consent prior to all trial-related procedures including HIV testing.
Male or female, aged between 18 and 65 years, inclusive.
Body weight between 40 and 90 kg, inclusive.
Newly diagnosed, previously untreated, drug susceptible pulmonary TB: presence of MTB complex and rapid molecular tests result confirming susceptibility to RIF and INH such as GeneXpert and/or HAIN MTBDR plus.
A chest X-ray (no older than 2 weeks) which, in the opinion of the Investigator, is consistent with TB.
Sputum positive on microscopy from concentrated sputum for acid-fast bacilli on at least one sputum sample (at least 1+ on the IUATLD/WHO scale).
The participant is willing to forgo consumption of foods high in tyramine for the period of taking study medication (See Appendix, section 20.2, page 92).
The participant is either unable to conceive/father children AND/OR his/her partner is unable to conceive/father children AND/OR they will consent to be using effective methods of contraception when engaging in heterosexual intercourse, as defined below:
a. Non-childbearing potential: i. Female participant/sexual partner of male participant: Bilateral oophorectomy, and/or hysterectomy or bilateral tubal ligation more than 12 months ago and/or has been postmenopausal with a history of no menses for at least 12 consecutive months ii. Male participant/sexual partner of female participant: Vasectomised or has had a bilateral orchidectomy minimally three months prior to screening iii. Male participants having a pregnant female partner or a male sexual partner: At least one barrier method has to be used in this case. b. Effective contraception methods: i. Female participants: Two methods, including methods that the patient's sexual partner(s) use. At least one must be a barrier method. Contraception must be practised for at least until 12 weeks after the last dose of DZD. ii. Male participants: Two methods, including methods that the patient's female sexual partner(s) use. At least one must be a barrier method. Effective contraception must be ensured for at least 16 weeks after the last dose of DZD.
Note: hormone-based contraception alone may not be reliable when taking RIF during continuation phase; therefore, hormone-based contraceptives alone cannot be used by female participants/female partners of male participants to prevent pregnancy.
Exclusion Criteria:
Circumstances that raise doubt about free, unconstrained consent to study participation (e.g. prisoner or mentally handicapped person)
Poor general condition where delay in treatment cannot be tolerated or death within four months is likely.
Poor social condition which would make it unlikely that the patient would be able to complete follow-up
The patient is pregnant or breast-feeding.
The patient is infected with HIV with a CD4 count <220 cells/mm3. If >220 cells/mm3, patients will be included only if any of the following is applicable:
The patient has a known intolerance to any of the study drugs or concomitant disorders or conditions for which study drugs or standard TB treatment are contraindicated
The patient has a history of, or current evidence of clinically relevant cardiovascular metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or any other condition that will influence treatment response, study adherence or survival in the judgement of the investigator, especially:
Any of the following laboratory findings at screening:
ECG findings in the screening ECG: (one or more):
Restricted medication:
Treatment with any other investigational drug within 1 month prior to enrolment or enrolment into other clinical (intervention) trials during participation.
Previous anti-TB treatment with drugs active against MTB within the last 3 months prior to screening.
Unable or unwilling to abide by the requirements regarding restricted medication or have taken restricted medication as described under section 12.6, page 58. Restricted medication includes the following drug classes:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Aurum Institute Tembisa Clinical Research Centre | Tembisa | Gauteng | 1632 | South Africa | ||
| Clinical HIV Research Unit (CHRU) University of the Witwatersrand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40645198 | Result | Minja LT, van der Feltz I, Manyama C, Mpagama S, Mhimbira F, Norena I, Sebe M, Rassool M, Wallis RS, Ntinginya N, Liyoyo A, Mbeya B, Wagnerberger L, Zumba T, Peter DD, Makkan H, Sloan DJ, Brake LT, Schildkraut JA, Aarnoutse R, McHugh TD, Wildner L, Boeree MJ, Geiter L, Cho YL, Aldana BH, Phillips PPJ, Hoelscher M, Svensson EM, Heinrich N; PanACEA consortium. Delpazolid in combination with bedaquiline, delamanid, and moxifloxacin for pulmonary tuberculosis (PanACEA-DECODE-01): a prospective, randomised, open-label, phase 2b, dose-finding trial. Lancet Infect Dis. 2025 Nov;25(11):1219-1229. doi: 10.1016/S1473-3099(25)00289-0. Epub 2025 Jul 8. | |
| 37280643 |
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Deidentified individual patient data, that underlie the results in published article(s) based on data from the trial which including text, tables, figures will be presented to various stakeholders. This reported will be presented to various stakeholder during various forums or meetings. First esults will be disclosed to participants, staff and our site Community Advisory Board. Thereafter we would invite several stakeholders from the community or visit their establishments to review study results. Simultaneously, the studying findings report will be sent to the various regulatory authorities, including the National Department of Health (NDoH). With NDoH and its divisions we will establish needs for further engagement and suggestions for policy or programmatic changes.
PD will be provided 1 - 2 years after and up to 5 years after the publication of the article on the results of the trial
IPD access will be provided for analyses of related to the aims of research described in the protocol and for individual patient data meta-analyses to researchers who provide a methodologically sound proposal to yhlee@ligachembio.com
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This study was initiated on 28 October 2021 (first signed informed consent) with the date of last participant who completed last study visit on 04 Sep 2023.
A total of 156 participants were screened. Of these, 76 participants were randomized to 1 of 5 arms, and subsequently received at least 1 dose of the study drug. The remaining 80 participants were considered to have been screen failures.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm1(D0) | Participants received the following medication for the duration of 16 weeks together with food.
Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| FG001 | Arm2(D400) | Participants received the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| FG002 | Arm3(D800-OD) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| FG003 | Arm4(D1200) | Participants received the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| FG004 | Arm5(D800-BD) | Participants received the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-Treat Population and Safety Population
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm1(D0) | Participants receive the following medication for the duration of 16 weeks together with food.
Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety Outcome : Proportion of Patients Experiencing Adverse Event | Participants with ≥ 1 TEAE, by severity, related Adverse events: possibly, probably, or definitely related to study drugs | Safety Population | Posted | Count of Participants | Participants | week0 - week52 |
|
From Week 0 to Week 52
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Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm1(D0) | BDM group
| 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastritis | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 25.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Seonghye Cheon | LigaChem Bioscience, Inc. | +82)02-6952-0689 | scheon@ligachembio.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 8, 2021 | Aug 22, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 15, 2023 | Aug 22, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007239 | Infections |
| D014397 | Tuberculosis, Pulmonary |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C000627008 | delpazolid |
| C493870 | bedaquiline |
| C516022 | OPC-67683 |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
Not provided
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| Experimental |
Participants receive the following medication for the duration of 16weeks together with food.
|
|
| Arm5(D800-BD) | Experimental | Participants receive the following medication for the duration of 16weeks together with food.
|
|
|
| Bedaquiline, Delamanid, Moxifloxacin | Drug | These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
|
|
| Week 0 - Week 16 |
| Efficacy Outcome: Changes in Mycobacterial Load Over Time on Treatment as Quantified by Time to Positivity in BD MGIT960® Liquid Media | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by time to positivity (TTP) in BD MGIT 960® liquid culture described by nonlinear mixed-effects methodology. Sputum samples were collected for BD MGIT960® Liquid Media culture at all time points during the treatment and follow-up phases, and this table shows TTP results. | Week 0 - Week 16 |
| Efficacy Outcome: Loewenstein-Jensen Solid Media Culture Results | Summary of Changes in Mycobacterial Load Over Time on Treatment as Quantified by Time to Culture Conversion in Loewenstein-Jensen Solid Media - Intent-to-Treat Population Sputum samples were collected for Loewenstein-Jensen Solid Media culture at at Week 0, Week 8, Week 12, Week 6 during the treatment and follow-up phases, and this table shows culture results, which are reported as: Positive, Negative, Contaminated, Missing. | Week 0 - Week 16 |
| Efficacy Outcome: The Proportion Converted by Day Corresponding to End of Each Week | Culture conversion was defined as 2 negative cultures without an intervening positive culture. Time was measured as time on treatment until the first negative culture (up to Week 16 Visit). 'Converted by Week x' shows proportion converted by day corresponding to end of each week, e.g., Week 2 = Day 14. | Week 0 - Week 16 |
| Efficacy Outcome: Time to Culture Conversion | Time to culture conversion was defined as 2 negative cultures without an intervening positive culture. Time was measured as time on treatment until the first negative culture (up to Week 16 Visit). | Week 0 - Week 16 |
| Efficacy Outcome : Relapse or Reinfection | A participant was positive for relapse or reinfection if they converted to culture negative by Week 8 and had 2 consecutive positive cultures after Week 16 of randomization, without an intervening negative. | Week0 - Week52 |
| Johannesburg |
| 2092 |
| South Africa |
| Ifakara Health Institute | Bagamoyo | Tanzania |
| National Institute for Medical Research (NIMR-MMRC) | Mbeya | Tanzania |
| Ki'bongoto Infectious Disease Hospital (KIDH) Kilimanjaro Clinical Research Institute (KCRI) | Moshi | Tanzania |
| Derived |
| Dierig A, Hoelscher M, Schultz S, Hoffmann L, Jarchow-MacDonald A, Svensson EM, Te Brake L, Aarnoutse R, Boeree M, McHugh TD, Wildner LM, Gong X, Phillips P, Minja LT, Ntinginya N, Mpagama S, Liyoyo A, Wallis RS, Sebe M, Mhimbira FA, Mbeya B, Rassool M, Geiter L, Cho YL, Heinrich N. A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis. Trials. 2023 Jun 6;24(1):382. doi: 10.1186/s13063-023-07354-5. |
| BG001 | Arm2(D400) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| BG002 | Arm3(D800-OD) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| BG003 | Arm4(D1200) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| BG004 | Arm5(D800-BD) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m2 |
|
| HIV status | Count of Participants | Participants |
|
| GeneXpert CT results | Count of Participants | Participants |
|
| OG001 | Arm2(D400) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| OG002 | Arm3(D800-OD) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| OG003 | Arm4(D1200) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
| OG004 | Arm5(D800-BD) | Participants receive the following medication for the duration of 16 weeks together with food.
Delpazolid: Delpazolid is not licensed yet. Current experience in humans upto Phase IIA. Dose according to randomization to dosing arms 2-5. Bedaquiline, Delamanid, Moxifloxacin: These three licensed drugs form the backbone of a new regimen to which delpazolid is added in arms 2-5. |
|
|
| Primary | Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_AUC0-24 | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Median | Full Range | mg/L*h | Week 0 - Week 16 |
|
|
|
| Primary | Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_Cmax | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Median | Full Range | mg/L | Week 0 - Week 16 |
|
|
|
| Primary | Efficacy Outcome: Exposure-response Analysis With TTP (Time to Positive)_Cmin | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by TTP (Time to positive) in BD MGIT960® liquid culture described by non linear mixed effects methodology. A population PK model was developed using NONMEM version 7.4.1. DZD PK is well-described by a two-compartment model with first-order absorption, first-order elimination and a proportional residual error. The final model included allometric scaling based on FFM. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Median | Full Range | mg/L | Week 0 - Week 16 |
|
|
|
| Secondary | Efficacy Outcome: BD MGIT960® Liquid Media Culture Results | Summary of Changes in Mycobacterial Load Over Time on Treatment as Quantified by Time to Positivity in BD MGIT960® Liquid Media - Intent to Treat Population Sputum samples were collected for BD MGIT960® Liquid Media culture at all time points during the treatment and follow-up phases, and this table shows culture results, which are reported as: Positive, Negative, Contaminated, Missing. Note: Contaminated cultures are shown as contaminated for the purpose of the overall result but are counted as missing for calculating summary statistics. The data recorded as 'Positive for MTB Complex with Contamination' are included as 'Positive' for MGIT result. However, the data from mean and median calculations for TTP (Time to positive) due to contamination. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Count of Participants | Participants | Week 0 - Week 16 |
|
|
|
| Secondary | Efficacy Outcome: Changes in Mycobacterial Load Over Time on Treatment as Quantified by Time to Positivity in BD MGIT960® Liquid Media | The efficacy of DZD was evaluated by measuring the change in mycobacterial load over time on treatment as quantified by time to positivity (TTP) in BD MGIT 960® liquid culture described by nonlinear mixed-effects methodology. Sputum samples were collected for BD MGIT960® Liquid Media culture at all time points during the treatment and follow-up phases, and this table shows TTP results. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Mean | Standard Deviation | days | Week 0 - Week 16 |
|
|
|
| Secondary | Efficacy Outcome: Loewenstein-Jensen Solid Media Culture Results | Summary of Changes in Mycobacterial Load Over Time on Treatment as Quantified by Time to Culture Conversion in Loewenstein-Jensen Solid Media - Intent-to-Treat Population Sputum samples were collected for Loewenstein-Jensen Solid Media culture at at Week 0, Week 8, Week 12, Week 6 during the treatment and follow-up phases, and this table shows culture results, which are reported as: Positive, Negative, Contaminated, Missing. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Count of Participants | Participants | Week 0 - Week 16 |
|
|
|
| Secondary | Efficacy Outcome: The Proportion Converted by Day Corresponding to End of Each Week | Culture conversion was defined as 2 negative cultures without an intervening positive culture. Time was measured as time on treatment until the first negative culture (up to Week 16 Visit). 'Converted by Week x' shows proportion converted by day corresponding to end of each week, e.g., Week 2 = Day 14. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Number | percentage of participants | Week 0 - Week 16 |
|
|
|
| Secondary | Efficacy Outcome: Time to Culture Conversion | Time to culture conversion was defined as 2 negative cultures without an intervening positive culture. Time was measured as time on treatment until the first negative culture (up to Week 16 Visit). | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Median | Inter-Quartile Range | Days | Week 0 - Week 16 |
|
|
|
| Secondary | Efficacy Outcome : Relapse or Reinfection | A participant was positive for relapse or reinfection if they converted to culture negative by Week 8 and had 2 consecutive positive cultures after Week 16 of randomization, without an intervening negative. | Intent to Treat Population; all randomized participants in the groups to which they were randomly assigned and who have taken at least one dose of study treatment. | Posted | Count of Participants | Participants | Week0 - Week52 |
|
|
|
| 15 |
| 0 |
| 15 |
| 8 |
| 15 |
| EG001 | Arm2(D400) | BDM + delpazolid 400 mg QD group | 0 | 15 | 0 | 15 | 7 | 15 |
| EG002 | Arm3(D800-OD) | BDM + delpazolid 800 mg QD group | 0 | 15 | 1 | 15 | 7 | 15 |
| EG003 | Arm4(D1200) | BDM + delpazolid 1200 mg QD group | 0 | 16 | 0 | 16 | 6 | 16 |
| EG004 | Arm5(D800-BD) | BDM + delpazolid 800 mg BID group | 0 | 15 | 2 | 15 | 9 | 15 |
| Anaemia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA 25.1 | Non-systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 25.1 | Non-systematic Assessment |
|
| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA 25.1 | Non-systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 25.1 | Non-systematic Assessment |
|
| Gamma glutamyl transferase increased | Investigations | MedDRA 25.1 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 25.1 | Non-systematic Assessment |
|
Not provided
Not provided
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Negative |
|
| Contaminated |
|
| Missing |
|
| Week 1 |
|
| Week 2 |
|
| Week 3 |
|
| Week 4 |
|
| Week 5 |
|
| Week 6 |
|
| Week 7 |
|
| Week 8 |
|
| Week 9 |
|
| Week 10 |
|
| Week 11 |
|
| Week 12 |
|
| Week 13 |
|
| Week 14 |
|
| Week 15 |
|
| Week 16 |
|
| Week 1 |
|
| Week 2 |
|
| Week 3 |
|
| Week 4 |
|
| Week 5 |
|
| Week 6 |
|
| Week 7 |
|
| Week 8 |
|
| Week 9 |
|
| Week 10 |
|
| Week 11 |
|
| Week 12 |
|
| Week 13 |
|
| Week 14 |
|
| Week 15 |
|
| Week 16 |
|
| Negative |
|
| Contaminated |
|
| Missing |
|
| Week 8 |
|
| Week 12 |
|
| Week 16 |
|
| Week 2 |
|
| Week 3 |
|
| Week 4 |
|
| Week 5 |
|
| Week 6 |
|
| Week 7 |
|
| Week 8 |
|
| Week 9 |
|
| Week 10 |
|
| Week 11 |
|
| Week 12 |
|
| Week 13 |
|
| Week 14 |
|
| Week 15 |
|
| Week 16 |
|
| Conversion by Week 8 and positive culture past week 12 |
|
| Did not convert by Week 8 |
|
| Relapsed or reinfected |
|
| Death |
|