Mycobacterium Infections, Nontuberculous
Conditions
Keywords
ALIS, ARIKAYCE
Brief summary
A study to evaluate the effectiveness of Liposomal Amikacin for Inhalation (LAI) 590 mg administered once daily (QD) when added to multi-drug regimen (MDR) in participants with Nontuberculous Mycobacterial (NTM) lung infection caused by Mycobacterium Avium Complex (MAC) that were refractory to treatment. Participants were randomized 2:1 to LAI 590 mg administered QD + MDR or MDR alone.
Detailed description
This is a randomized, open-label, multicenter study of LAI in adult participants with NTM lung infections caused by MAC that were refractory to treatment. Participants received either LAI 590 mg administered QD by inhalation plus a multidrug regimen, hereafter referred to as LAI + MDR or a multidrug regimen alone, hereafter referred to as MDR alone for a minimum of 8 months. Participants who demonstrated culture conversion by Month 6 went on to complete a treatment course of 12 months, starting from the first of 3 negative cultures that defined culture conversion. Sputum culture results were made available to the site after the Month 6 sputum result was known, in time for the Month 8 visit. Prior to the Month 8 visit, the culture results from Baseline to Month 6 inclusively were blinded to the site and Sponsor. The results were blinded to reduce the potential for bias in an open-label study. At Month 8 (-28 to +7 days), after all sputum culture results were made available to the site only, up to and including Month 6, participants were assessed as converters or non-converters. A converter was defined as a participant who had 3 consecutive monthly MAC-negative sputum cultures at any time within the first 6 months of the study. Relapse or recurrence was defined as having MAC-positive sputum cultures in liquid broth media (agar negative) for 3 or more consecutive months, or having at least 1 MAC-positive sputum culture on solid media (agar positive) after achieving culture conversion. A non-converter was defined as a participant who did not have 3 consecutive monthly MAC-negative sputum cultures at any time within the first 6 months of the study. All converters remained in the study. Converters who, after culture conversion, subsequently had MAC-positive sputum cultures in liquid broth media (agar negative) for 1 or 2 consecutive months only by Month 6 also remained in the study. Participants who remained in the study continued their randomized treatment regimen until they completed a total of 12 months of treatment (EOT), starting from the first of 3 negative cultures that defined culture conversion. These participants returned after the EOT visit for 28 days, 3, 6, and 12 months off-treatment follow-up visits. The 12 months off-treatment follow-up visit was the end of study (EOS) visit. No NTM treatment was administered during the off-treatment phase. At Month 8, all non-converters as assessed at the Month 6 visit were discontinued from Study INS-212. Participants who experienced a relapse or recurrence by Month 6 also discontinued from Study INS-212 at their Month 8 visit. These participants were potentially eligible to enter a separate open-label study of LAI (Study INS-312), provided all entry criteria were met for that study.
Interventions
DRUGLAI (Liposomal Amikacin for Inhalation) 590 mg
LAI 590 mg QD, administered by inhaling drug product that had been aerosolized in an eFlow nebulizer over approximately 14 minutes.
Sponsors
Insmed Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Be continually positive for MAC on sputum culture while adhering to a multi-drug treatment regimen for a minimum duration of 6 months which is either ongoing or was completed no more than 12 months before screening 2. Be diagnosed with MAC NTM lung infection with evidence of nodular bronchiectasis and/or fibrocavitary disease by chest CT 3. Be willing to adhere to multi-drug treatment regimen during the course of the study
Exclusion criteria
1. Patients with cystic fibrosis 2. Positive pregnancy test or lactation at screening. All women of child bearing potential will be tested. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally sterile. 3. Active pulmonary tuberculosis requiring treatment at screening 4. History of lung transplantation 5. Prior exposure to LAI (including clinical study).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm | by Month 6 | Sputum specimens were collected at Screening (Visit 1), Baseline (Visit 2), and at Visits 3 (Month 1) through 8 (Month 6). A negative culture result reflected a negative culture result for all sputum samples collected at each visit. Participants met the primary endpoint of culture conversion by Month 6 if they had 3 consecutive monthly MAC-negative sputum cultures during the first 6 months of the study. A participant needed to achieve the first of 3 consecutive negative sputum cultures (that defined culture conversion) by Month 4 in order to meet the primary endpoint by Month 6. Each participant in the intent to treat (ITT) population (ie, all randomized participants) was classified as either a converter or non-converter by Month 6. |
| Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone | up to Month 19 | Sputum specimens were collected at screening, baseline (Day 1), during treatment, and at Months 1, 3, 6, and 12 months off treatment. Culture conversion with durability was defined as achieving culture conversion by Month 6 and then having no more than 2 consecutive broth positive cultures and no Agar positive culture up to 3 months off treatment. Converters with missing broth or Agar sputum culture result after Month 6 up to 3 months off treatment were considered as not achieving culture conversion with durability except those participants who are unable to produce sputum despite reasonable efforts, as reported by source documentation. Participants who had relapse/recurrence, had rescue medication and/or died before reaching 3 months off treatment were considered as not achieving culture conversion with durability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone | up to Month 16 | Sustained conversion was evaluated in participants who completed at least 12 months of treatment from the start of culture conversion. Sustained conversion was defined as conversion (3 consecutive negative monthly sputum samples) by Month 6 with no positive agar media culture or no more than 2 broth media cultures up to and including the time point. Participants who did not convert were considered non-sustained conversions. |
| Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm | at Month 6 | A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and at Month 6. The standardized protocol based on the ATS guidelines was used. The 6MWT was conducted by a site member who was blinded to the participant's open-label treatment assignment. The analysis of the change from Baseline (Day 1) to Month 6 in the 6MWT distance was performed after the last participant completed Month 6 and his/her 6MWT distance data were available. |
| Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score | at Month 6 | The SGRQ was completed before administration of study drug at Baseline (Day 1) and Months 3, 6, 8, and 12, and at the EOT visit and the 3 months off treatment visit. The SGRQ is a self-administered questionnaire that has been validated in participants with airways disease, specifically in participants with bronchiectasis. The SGRQ assesses health-related quality of life in participants with chronic pulmonary disease by evaluating 3 health domains: symptoms (distress caused by respiratory symptoms); activity (effects of disturbances on mobility and physical activity); and impacts (the effect of disease on factors such as employment, personal control of one's health, and need for medication). A composite total score is derived as the sum of domain scores for symptoms, activity, and impact (0 = best possible score and 100 = worst possible score). A within patient reduction from baseline in score of 4 units is generally recognized as a clinically meaningful improvement in quality of life. |
| Change in 6-Minute Walk Test (6MWT) Distance at EOT in the LAI Arm Compared to a Multi-drug Regimen Alone | up to Month 16 | A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and up to EOT or Month 16. The standardized protocol based on the ATS guidelines was used. The 6MWT was conducted by a site member who was blinded to the participant's open-label treatment assignment. |
| Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm | by Month 6 | The time to culture conversion was defined by the date of the first of at least 3 consecutive monthly culture specimens that were Mycobacterium avium complex (MAC)-negative. The 25th percentile time to conversion is the estimated time taken for 25% of participants to convert. The 50th percentile time to conversion is the estimated time taken for 50% of participants to convert. |
Participant flow
Recruitment details
This study was conducted at 127 sites in 18 countries.
Pre-assignment details
Participant flow table reflects the disposition through end of the study (Month 28). The deaths under Reasons for Discontinuation reflect the primary reason (according to investigator's judgment) that the participant discontinued and does not represent all deaths in the trial.
Participants by arm
| Arm | Count |
|---|---|
| LAI + Multi-drug Regimen Participants received LAI 590 mg QD in addition to their already prescribed anti-mycobacterial regimen (based on the 2007 ATS/IDSA Guidelines); LAI 590 mg QD, administered by inhaling drug product that had been aerosolized in an eFlow nebulizer over approximately 14 minutes | 224 |
| Multi-drug Regimen Participants received their already prescribed anti-mycobacterial regimen (based on the 2007 ATS/IDSA Guidelines) | 112 |
| Total | 336 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 1 |
| Overall Study | Death | 9 | 7 |
| Overall Study | Other Not Specified | 12 | 0 |
| Overall Study | Physician Decision | 4 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Rescue Medication | 2 | 0 |
| Overall Study | Withdrawal by Subject | 22 | 5 |
Baseline characteristics
| Characteristic | Total | Multi-drug Regimen | LAI + Multi-drug Regimen |
|---|---|---|---|
| Age, Continuous | 64.7 years STANDARD_DEVIATION 9.77 | 64.9 years STANDARD_DEVIATION 10.16 | 64.6 years STANDARD_DEVIATION 9.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 313 Participants | 102 Participants | 211 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 5 Participants | 3 Participants |
| If female, is participant of childbearing potential? No | 214 Participants | 62 Participants | 152 Participants |
| If female, is participant of childbearing potential? Yes | 19 Participants | 6 Participants | 13 Participants |
| If not childbearing potential, specify Naturally Sterile | 0 Participants | 0 Participants | 0 Participants |
| If not childbearing potential, specify Postmenopausal | 164 Participants | 50 Participants | 114 Participants |
| If not childbearing potential, specify Surgically Sterile | 50 Participants | 12 Participants | 38 Participants |
| Multidrug regimen prior to enrollment Off treatment for at least 3 months | 34 Participants | 11 Participants | 23 Participants |
| Multidrug regimen prior to enrollment On treatment | 302 Participants | 101 Participants | 201 Participants |
| Prior nebulized IV amikacin | 39 Participants | 15 Participants | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 83 Participants | 25 Participants | 58 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) White | 235 Participants | 77 Participants | 158 Participants |
| Region Asia (excluding Japan) | 20 Participants | 6 Participants | 14 Participants |
| Region Japan | 48 Participants | 14 Participants | 34 Participants |
| Region North America | 159 Participants | 55 Participants | 104 Participants |
| Region Rest of World | 109 Participants | 37 Participants | 72 Participants |
| Sex: Female, Male Female | 233 Participants | 68 Participants | 165 Participants |
| Sex: Female, Male Male | 103 Participants | 44 Participants | 59 Participants |
| Smoking status (includes e-cigarettes) Current smoker | 36 Participants | 10 Participants | 26 Participants |
| Smoking status (includes e-cigarettes) Not a current smoker | 300 Participants | 102 Participants | 198 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 223 | 8 / 112 |
| other Total, other adverse events | 199 / 223 | 72 / 112 |
| serious Total, serious adverse events | 45 / 223 | 23 / 112 |
Outcome results
Primary
Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm
Sputum specimens were collected at Screening (Visit 1), Baseline (Visit 2), and at Visits 3 (Month 1) through 8 (Month 6). A negative culture result reflected a negative culture result for all sputum samples collected at each visit. Participants met the primary endpoint of culture conversion by Month 6 if they had 3 consecutive monthly MAC-negative sputum cultures during the first 6 months of the study. A participant needed to achieve the first of 3 consecutive negative sputum cultures (that defined culture conversion) by Month 4 in order to meet the primary endpoint by Month 6. Each participant in the intent to treat (ITT) population (ie, all randomized participants) was classified as either a converter or non-converter by Month 6.
Time frame: by Month 6
Population: The ITT population was the set of all randomized participants. Participants were classified according to their assigned treatment. There was a total of 336 participants in the ITT population, including 224 participants in the LAI + MDR arm and 112 participants in the MDR alone arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LAI + Multi-drug Regimen | Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm | Converter | 65 Participants |
| LAI + Multi-drug Regimen | Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm | Non-Converter | 159 Participants |
| Multi-drug Regimen | Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm | Converter | 10 Participants |
| Multi-drug Regimen | Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm | Non-Converter | 102 Participants |
Comparison: The proportion of participants achieving culture conversion by Month 6 was analyzed using the Cochran-Mantel-Haenszel test, stratified by smoking status and prior multi-drug regimen. The treatment comparison was tested at two-sided significance level of 0.05. The null hypothesis assumed that culture conversion by Month 6 is independent of treatment, and the alternative hypothesis assumed that culture conversion by Month 6 is associated with treatment.p-value: <0.0001Cochran-Mantel-Haenszel
Primary
Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone
Sputum specimens were collected at screening, baseline (Day 1), during treatment, and at Months 1, 3, 6, and 12 months off treatment. Culture conversion with durability was defined as achieving culture conversion by Month 6 and then having no more than 2 consecutive broth positive cultures and no Agar positive culture up to 3 months off treatment. Converters with missing broth or Agar sputum culture result after Month 6 up to 3 months off treatment were considered as not achieving culture conversion with durability except those participants who are unable to produce sputum despite reasonable efforts, as reported by source documentation. Participants who had relapse/recurrence, had rescue medication and/or died before reaching 3 months off treatment were considered as not achieving culture conversion with durability.
Time frame: up to Month 19
Population: The ITT population was the set of all randomized participants. Participants were classified according to their assigned treatment. There was a total of 336 participants in the ITT population, including 224 participants in the LAI + MDR arm and 112 participants in the MDR alone arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LAI + Multi-drug Regimen | Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone | Durable Conversion | 36 Participants |
| LAI + Multi-drug Regimen | Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone | Non-Durable Conversion | 188 Participants |
| Multi-drug Regimen | Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone | Durable Conversion | 0 Participants |
| Multi-drug Regimen | Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone | Non-Durable Conversion | 112 Participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score
The SGRQ was completed before administration of study drug at Baseline (Day 1) and Months 3, 6, 8, and 12, and at the EOT visit and the 3 months off treatment visit. The SGRQ is a self-administered questionnaire that has been validated in participants with airways disease, specifically in participants with bronchiectasis. The SGRQ assesses health-related quality of life in participants with chronic pulmonary disease by evaluating 3 health domains: symptoms (distress caused by respiratory symptoms); activity (effects of disturbances on mobility and physical activity); and impacts (the effect of disease on factors such as employment, personal control of one's health, and need for medication). A composite total score is derived as the sum of domain scores for symptoms, activity, and impact (0 = best possible score and 100 = worst possible score). A within patient reduction from baseline in score of 4 units is generally recognized as a clinically meaningful improvement in quality of life.
Time frame: at Month 6
Population: The ITT population was the set of all randomized participants. Participants were classified according to their assigned treatment. There was a total of 336 participants in the ITT population, including 224 participants in the LAI + MDR arm and 112 participants in the MDR alone arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAI + Multi-drug Regimen | Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score | SGRQ Total Score at Baseline: | 36.555 score on a scale | Standard Deviation 21.3777 |
| LAI + Multi-drug Regimen | Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score | SGRQ Total Score at Month 6: | 38.715 score on a scale | Standard Deviation 22.3559 |
| LAI + Multi-drug Regimen | Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score | Change from Baseline to Month 6: | 2.009 score on a scale | Standard Deviation 13.4128 |
| Multi-drug Regimen | Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score | Change from Baseline to Month 6: | -1.312 score on a scale | Standard Deviation 11.6216 |
| Multi-drug Regimen | Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score | SGRQ Total Score at Baseline: | 38.409 score on a scale | Standard Deviation 21.5753 |
| Multi-drug Regimen | Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score | SGRQ Total Score at Month 6: | 37.368 score on a scale | Standard Deviation 23.6868 |
Secondary
Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm
A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and at Month 6. The standardized protocol based on the ATS guidelines was used. The 6MWT was conducted by a site member who was blinded to the participant's open-label treatment assignment. The analysis of the change from Baseline (Day 1) to Month 6 in the 6MWT distance was performed after the last participant completed Month 6 and his/her 6MWT distance data were available.
Time frame: at Month 6
Population: The ITT population was the set of all randomized participants. Participants were classified according to their assigned treatment. There was a total of 336 participants in the ITT population, including 224 participants in the LAI + MDR arm and 112 participants in the MDR alone arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LAI + Multi-drug Regimen | Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm | Baseline | 424.2 meters | Standard Deviation 1.12 |
| LAI + Multi-drug Regimen | Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm | Month 6 | 420.6 meters | Standard Deviation 4.73 |
| LAI + Multi-drug Regimen | Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm | Change from Baseline to Month 6 | -3.6 meters | Standard Deviation 3.25 |
| Multi-drug Regimen | Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm | Baseline | 420.9 meters | Standard Deviation 0.48 |
| Multi-drug Regimen | Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm | Month 6 | 420.3 meters | Standard Deviation 2.57 |
| Multi-drug Regimen | Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm | Change from Baseline to Month 6 | -0.5 meters | Standard Deviation 4.2 |
Comparison: This was analyzed using a mixed model repeated measures (MMRM) analysis of change from Baseline at Months 4\&6. MMRM included treatment, month, treatment-by-month interaction, combination of smoking status \& prior MDR (4 levels: Yes/Yes, Yes/No, No/Yes, and No/No) as fixed factors, baseline 6MWD as a covariate \& baseline 6MWD-by-month interaction. An unstructured covariance matrix was used for the MMRM.p-value: 0.7804Mixed Model Repeated Measures (MMRM)
Secondary
Change in 6-Minute Walk Test (6MWT) Distance at EOT in the LAI Arm Compared to a Multi-drug Regimen Alone
A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and up to EOT or Month 16. The standardized protocol based on the ATS guidelines was used. The 6MWT was conducted by a site member who was blinded to the participant's open-label treatment assignment.
Time frame: up to Month 16
Population: Due to the widely varying timepoints that makeup the EOT visit, this was not considered an appropriate analysis and was not performed.
Secondary
Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone
Sustained conversion was evaluated in participants who completed at least 12 months of treatment from the start of culture conversion. Sustained conversion was defined as conversion (3 consecutive negative monthly sputum samples) by Month 6 with no positive agar media culture or no more than 2 broth media cultures up to and including the time point. Participants who did not convert were considered non-sustained conversions.
Time frame: up to Month 16
Population: The ITT population was the set of all randomized participants. Participants were classified according to their assigned treatment. There was a total of 336 participants in the ITT population, including 224 participants in the LAI + MDR arm and 112 participants in the MDR alone arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LAI + Multi-drug Regimen | Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone | Sustained Conversion | 41 Participants |
| LAI + Multi-drug Regimen | Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone | Non-Sustained Conversion | 183 Participants |
| Multi-drug Regimen | Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone | Sustained Conversion | 3 Participants |
| Multi-drug Regimen | Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone | Non-Sustained Conversion | 109 Participants |
Secondary
Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm
The time to culture conversion was defined by the date of the first of at least 3 consecutive monthly culture specimens that were Mycobacterium avium complex (MAC)-negative. The 25th percentile time to conversion is the estimated time taken for 25% of participants to convert. The 50th percentile time to conversion is the estimated time taken for 50% of participants to convert.
Time frame: by Month 6
Population: There was a total of 336 participants in the ITT population, including 224 participants in the LAI + MDR arm and 112 participants in the MDR alone arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LAI + Multi-drug Regimen | Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm | 25th Percentile | 2.13 months |
| LAI + Multi-drug Regimen | Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm | 50th Percentile | NA months |
| Multi-drug Regimen | Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm | 25th Percentile | NA months |
| Multi-drug Regimen | Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm | 50th Percentile | NA months |
Comparison: Kaplan Meier estimates for the distribution of time to culture conversion were constructed for treatment arms. The treatment comparison was made using the stratified log rank test for the ITT population. The estimated median time to culture conversion for each treatment arm was not estimable. The time to culture conversion was analyzed using Cox regression model to estimate hazards ratio.p-value: <0.000195% CI: [2.01, 7.63]Regression, Cox