Clostridium Difficile Infection
Conditions
Keywords
Clostridium difficile infection, Post-antibiotic diarrhea
Brief summary
This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD).
Detailed description
Subjects selected to participate in the study are treated either with cadazolid or vancomycin for 10 days. At the end of treatment, clinical cure is assessed; subjects are then followed-up to assess any disease recurrence.
Interventions
DRUGCadazolid
Cadazolid 250 mg as oral suspension twice daily.
DRUGVancomycin
Vancomycin 125 mg as oral capsules 4 times daily
Placebo matching cadazolid and administered orally twice daily
Placebo capsules matching vancomycin and administered orally 4 times per day
Sponsors
Actelion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent. * Male or female ≥ 18 years of age. Females of childbearing potential must agree to use an adequate and reliable method of contraception. * Subject with a diagnosis of mild-moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with \> 3 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization.
Exclusion criteria
* More than one previous episode of CDAD in the 3-month period prior to randomization. * Evidence of life-threatening or fulminant CDAD. * Likelihood of death within 72 hours from any cause. * History of inflammatory colitides, chronic abdominal pain, or chronic diarrhea. * Antimicrobial treatment active against CDAD administered for \> 24 hours except for metronidazole treatment failures (MTF) * Known hypersensitivity or contraindication to study drugs, oxazolidinones, or quinolones. * Unable or unwilling to comply with all protocol requirements. * Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population | Up to Day 12 on average (end-of-treatment + 2 days) | Clinical Cure is defined as: • Resolution of Diarrhea (ROD) (≤ 3 unformed bowel movement (UBM) per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant (FMT) between first dose of study drug and 2 days after EOT (inclusive). CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below. |
| Clinical Cure Rate (CCR) in the Per-protocol Population | Up to Day 12 on average (end-of-treatment + 2 days) | Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT. CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population | Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) | Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The main analysis is performed on the modified intent-to-treat set (mITT). |
| Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Up to Day 10 | Resolution of Diarrhea (ROD) is defined as no more than 3 unformed bowel movements per day for at least two consecutive days for subjects on study treatment. The Kaplan-Meier estimates (KM estimates) for having an event (ROD) are reported for each time point. |
| Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | Baseline to End of Treatment (10 days after starting study drug) + 2 days | CDI-DaySyms PRO is a questionnaire assessing 10 symptoms relevant to subjects with CDAD and grouped into 3 domains: Diarrhea symptoms, Abdominal symptoms and Systemic/Other. The subjects rate the severity of each item as None, Mild, Moderate, Severe or Very severe, converted to numeric scores from 0 to 4, respectively. The daily domain score is calculated as the mean of the non-missing responses for that domain on that day. A negative value for change from baseline corresponds to an improvement in domain score. The three domains are evaluated in a hierarchical manner, starting with Diarrhea Symptoms, then Abdominal Symptoms, and finally Systemic/Other Symptoms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population | Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) | ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below. |
| Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5 | Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days) | ISR rate (%) is the percentage of subjects assessed as Sustained Cure at Visit 5, according to the investigator's own judgement. Sustained Cure is defined for each subject having Clinical Cure and no recurrence. Subjects with missing assessment are considered as having 'Not Sustained Cure' for the analysis. ISR rate is used as a supportive measure of the secondary efficacy endpoint (SCR). Analyses are performed on the modified intent-to-treat set (mITT). |
| Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population | Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) | ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. ICR rate (%) is the percentage of subjects with ICR assessed as cured. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below. |
| Sustained Cure Rate (SCR) in the Per-protocol Population | Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) | Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The analyses performed on the modified intent-to- treat set (mITT) are repeated on the per-protocol set (PPS) for sensitivity. |
| Recurrence Rate | Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days) | Recurrence is defined as the occurrence of a new episode of diarrhea (\> 3 unformed bowel movements on any day between end-of-treatment + 3 days and end-of-treatment + 30 days ) Recurrence rates is the percentage of subjects assessed as having a recurrence out of subjects with Clinical Cure. |
Participant flow
Recruitment details
1128 patients at 105 sites in 15 countries were screened, among whom 631 were randomized at 96 sites in 14 countries worldwide.
Pre-assignment details
Among the 631 subjects randomized, 22 were excluded from all the analyses due to potential data integrity issues resulting in 609 total participants considered for the analyses. From the 22 excluded patients no serious adverse events (AEs) or study drug discontinuation information were reported. All reported AEs were mild or moderate in intensity.
Participants by arm
| Arm | Count |
|---|---|
| Cadazolid Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days | 290 |
| Vancomycin Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days | 301 |
| Total | 591 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 11 | 15 |
| Overall Study | Lost to Follow-up | 4 | 8 |
| Overall Study | Physician Decision | 8 | 9 |
| Overall Study | Sponsor Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 18 |
Baseline characteristics
| Characteristic | Cadazolid | Vancomycin | Total |
|---|---|---|---|
| Age, Customized 18-64 years | 139 Participants | 152 Participants | 291 Participants |
| Age, Customized 65-74 years | 64 Participants | 60 Participants | 124 Participants |
| Age, Customized 75 years and older | 87 Participants | 89 Participants | 176 Participants |
| CDAD episode type strata First occurrence | 235 Participants | 246 Participants | 481 Participants |
| CDAD episode type strata First recurrence | 55 Participants | 55 Participants | 110 Participants |
| CDAD severity at baseline Mild-Moderate | 216 Participants | 227 Participants | 443 Participants |
| CDAD severity at baseline Severe | 54 Participants | 57 Participants | 111 Participants |
| CDAD severity at baseline Unable to determine | 20 Participants | 17 Participants | 37 Participants |
| Initial strain of Clostridium difficile Hypervirulent strains | 75 Participants | 88 Participants | 163 Participants |
| Initial strain of Clostridium difficile Non-hypervirulent strains | 181 Participants | 183 Participants | 364 Participants |
| Initial strain of Clostridium difficile Unable to determine | 34 Participants | 30 Participants | 64 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 15 Participants | 27 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 8 Participants | 13 Participants |
| Race/Ethnicity, Customized Whtie | 266 Participants | 271 Participants | 537 Participants |
| Region of Enrollment Canada | 15 Participants | 16 Participants | 31 Participants |
| Region of Enrollment Europe | 121 Participants | 124 Participants | 245 Participants |
| Region of Enrollment Other | 52 Participants | 54 Participants | 106 Participants |
| Region of Enrollment United States | 102 Participants | 107 Participants | 209 Participants |
| Sex: Female, Male Female | 187 Participants | 183 Participants | 370 Participants |
| Sex: Female, Male Male | 103 Participants | 118 Participants | 221 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 294 | 15 / 307 |
| other Total, other adverse events | 47 / 294 | 51 / 307 |
| serious Total, serious adverse events | 35 / 294 | 46 / 307 |
Outcome results
Primary
Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population
Clinical Cure is defined as: • Resolution of Diarrhea (ROD) (≤ 3 unformed bowel movement (UBM) per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant (FMT) between first dose of study drug and 2 days after EOT (inclusive). CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.
Time frame: Up to Day 12 on average (end-of-treatment + 2 days)
Population: Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population | 81 Percentage of participants |
| Vancomycin | Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population | 85.7 Percentage of participants |
95% CI: [-10.7, 1.3]
Comparison: Sensitivity analysis with imputation for a single day with missing UBM data between one day before end-of-treatment (EOT) and 2 days after EOT95% CI: [-9.6, 2.3]
Primary
Clinical Cure Rate (CCR) in the Per-protocol Population
Clinical Cure (CC) is defined as: • Resolution of Diarrhea (≤ 3 unformed bowel movement per day for at least 2 consecutive days) on study treatment and maintained for 2 days after end-of-treatment (EOT), AND • No additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) or fecal microbiota transplant between first dose of study drug and 2 days after EOT. CCR is the percentage of subjects with Clinical Cure. Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.
Time frame: Up to Day 12 on average (end-of-treatment + 2 days)
Population: per-protocol population: all subjects from the mITT population without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Clinical Cure Rate (CCR) in the Per-protocol Population | 86.6 Percentage of participants |
| Vancomycin | Clinical Cure Rate (CCR) in the Per-protocol Population | 91.5 Percentage of participants |
95% CI: [-10.4, 0.6]
Secondary
Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores
CDI-DaySyms PRO is a questionnaire assessing 10 symptoms relevant to subjects with CDAD and grouped into 3 domains: Diarrhea symptoms, Abdominal symptoms and Systemic/Other. The subjects rate the severity of each item as None, Mild, Moderate, Severe or Very severe, converted to numeric scores from 0 to 4, respectively. The daily domain score is calculated as the mean of the non-missing responses for that domain on that day. A negative value for change from baseline corresponds to an improvement in domain score. The three domains are evaluated in a hierarchical manner, starting with Diarrhea Symptoms, then Abdominal Symptoms, and finally Systemic/Other Symptoms.
Time frame: Baseline to End of Treatment (10 days after starting study drug) + 2 days
Population: All subjects from the modified intent-to-treat population, excluding those who participated in the validation sub-study. No imputation of missing scores is performed prior to deriving response status. Subjects with missing values at baseline or at Day 3 are considered to be non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cadazolid | Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | Diarrhea symptoms | -1.242 Scores on a scale |
| Cadazolid | Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | Abdominal symptoms | -0.669 Scores on a scale |
| Cadazolid | Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | Other symptoms | -0.67 Scores on a scale |
| Vancomycin | Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | Diarrhea symptoms | -1.199 Scores on a scale |
| Vancomycin | Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | Abdominal symptoms | -0.693 Scores on a scale |
| Vancomycin | Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores | Other symptoms | -0.731 Scores on a scale |
Comparison: Comparison of the diarrhea domain scoresp-value: 0.687195% CI: [-0.26, 0.17]ANOVA
Comparison: Comparison of the abdominal symptoms domain scoresp-value: 0.783395% CI: [-0.15, 0.2]ANOVA
Comparison: Comparison of the other symptoms domain scoresp-value: 0.414595% CI: [-0.09, 0.21]ANOVA
Secondary
Kaplan-Meier Estimates for Resolution of Diarrhea (ROD)
Resolution of Diarrhea (ROD) is defined as no more than 3 unformed bowel movements per day for at least two consecutive days for subjects on study treatment. The Kaplan-Meier estimates (KM estimates) for having an event (ROD) are reported for each time point.
Time frame: Up to Day 10
Population: Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 1 | 51.0 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 2 | 64.5 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 3 | 69.7 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 4 | 73.8 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 5 | 77.9 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 6 | 77.9 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 7 | 79.7 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 8 | 81.0 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 9 | 81.0 KM estimate (% subjects with ROD) |
| Cadazolid | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 10 | 81.0 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 8 | 85.7 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 1 | 45.8 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 6 | 81.4 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 2 | 59.8 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 10 | 85.7 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 3 | 67.8 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 7 | 83.7 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 4 | 72.8 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 9 | 85.7 KM estimate (% subjects with ROD) |
| Vancomycin | Kaplan-Meier Estimates for Resolution of Diarrhea (ROD) | Day 5 | 78.4 KM estimate (% subjects with ROD) |
p-value: 0.779495% CI: [0.86, 1.24]Log Rank
Secondary
Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population
Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The main analysis is performed on the modified intent-to-treat set (mITT).
Time frame: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
Population: Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population | 63.4 Percentage of subjects |
| Vancomycin | Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population | 61.8 Percentage of subjects |
95% CI: [-6.1, 9.4]
Other Pre-specified
Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population
ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the modified intent-to-treat set (mITT) are reported below.
Time frame: Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
Population: Modified intent-to-treat population: all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population | 87.2 Percentage of participants |
| Vancomycin | Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population | 88.4 Percentage of participants |
Comparison: Exploratory analysis95% CI: [-6.5, 4.2]
Other Pre-specified
Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population
ICR rate (%) is the percentage of subjects with clinical response assessed as cured according to the investigator's own judgement. ICR rate (%) is the percentage of subjects with ICR assessed as cured. Subjects with missing assessment are considered as not cured for the analysis. ICR rate is used as a supportive measure of the primary efficacy endpoint (CCR). Analyses are performed on two analysis sets. Results on the per-protocol set (PPS) are reported below.
Time frame: Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
Population: Per-protocol population: all subjects from the mITT analysis set without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population | 91.1 Percentage of participants |
| Vancomycin | Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population | 92.7 Percentage of participants |
Comparison: Exploratory analysis95% CI: [-6.5, 3.3]
Other Pre-specified
Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5
ISR rate (%) is the percentage of subjects assessed as Sustained Cure at Visit 5, according to the investigator's own judgement. Sustained Cure is defined for each subject having Clinical Cure and no recurrence. Subjects with missing assessment are considered as having 'Not Sustained Cure' for the analysis. ISR rate is used as a supportive measure of the secondary efficacy endpoint (SCR). Analyses are performed on the modified intent-to-treat set (mITT).
Time frame: Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days)
Population: Modified intent-to-treat population (mITT): all subjects who received at least one dose of study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5 | 69.3 Percentage of participants |
| Vancomycin | Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5 | 60.5 Percentage of participants |
Comparison: Exploratory analysis95% CI: [1.1, 16.4]
Other Pre-specified
Recurrence Rate
Recurrence is defined as the occurrence of a new episode of diarrhea (\> 3 unformed bowel movements on any day between end-of-treatment + 3 days and end-of-treatment + 30 days ) Recurrence rates is the percentage of subjects assessed as having a recurrence out of subjects with Clinical Cure.
Time frame: Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days)
Population: Subjects from the modified intent-to-treat analysis set (mITT) with clinical cure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Recurrence Rate | 15.7 Percentage of participants |
| Vancomycin | Recurrence Rate | 17.8 Percentage of participants |
Other Pre-specified
Sustained Cure Rate (SCR) in the Per-protocol Population
Sustained Cure is defined for each subject having Clinical Cure and no recurrence. SCR is the percentage of subjects with Sustained Cure. The analyses performed on the modified intent-to- treat set (mITT) are repeated on the per-protocol set (PPS) for sensitivity.
Time frame: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
Population: Per-protocol population: all subjects from the mITT population without protocol deviations that might affect the evaluation of the effect of the study drug on the primary variable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cadazolid | Sustained Cure Rate (SCR) in the Per-protocol Population | 67.6 Percentage of participants |
| Vancomycin | Sustained Cure Rate (SCR) in the Per-protocol Population | 64.9 Percentage of participants |
95% CI: [-5.5, 10.9]