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This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cadazolid | Experimental | Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days |
|
| Vancomycin | Active Comparator | Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cadazolid | Drug | Cadazolid 250 mg as oral suspension twice daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to Day 12 on average (end-of-treatment + 2 days) |
| 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. | Up to Day 12 on average (end-of-treatment + 2 days) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anne Claire Marrast, MD | Actelion | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30709665 | Derived | Gerding DN, Cornely OA, Grill S, Kracker H, Marrast AC, Nord CE, Talbot GH, Buitrago M, Gheorghe Diaconescu I, Murta de Oliveira C, Preotescu L, Pullman J, Louie TJ, Wilcox MH. Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. Lancet Infect Dis. 2019 Mar;19(3):265-274. doi: 10.1016/S1473-3099(18)30614-5. Epub 2019 Jan 29. | |
| 29680101 |
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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.
1128 patients at 105 sites in 15 countries were screened, among whom 631 were randomized at 96 sites in 14 countries worldwide.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cadazolid | Subjects with Clostridium difficile-associated diarrhea (CDAD) received oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times a day (qid) for 10 days. Subjects were followed up for 30 days after the last dose of cadazolid. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up) |
| FG001 | Vancomycin | Subjects with CDAD received oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days. Subjects were followed up for 30 day after the last dose of vancomycin. Subjects who had a first recurrence of CDAD during the follow-up period were offered to enter a re-treatment extension period with cadazolid (10 days of cadazolid + 30-day follow up) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The modified-intent-to-treat population (mITT) was used: all subjects who have received at least one dose of the study drug and had a confirmed diagnosis of CDAD, and excluding 22 randomized subjects due to potential data integrity issues.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cadazolid | Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days |
| BG001 | Vancomycin | Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| 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 | 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to Day 12 on average (end-of-treatment + 2 days) |
|
Serious and frequent adverse events are reported from study treatment initiation up to Day 17 on average (i.e., 7 days after end-of-treatment or study withdrawal) and all-cause mortality up to Day 40 on average (i.e. 28 to 32 days after end-of-treatment or study withdrawal)
294 subjects who received at least one dose of cadazolid (cadazolid arm) and 307 subjects who received at least one dose of vancomycin (vancomycin arm) were included in the safety analysis. The median duration of treatment was 10 days in both arms.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cadazolid | oral cadazolid 250 mg twice daily (bid) for 10 days | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Clostridium difficile infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| clinical trial disclosure desk | Actelion Pharmaceuticals Ltd | 0041615656565 | clinical-trials-disclosure@its.jnj.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 22, 2015 | Apr 9, 2018 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 19, 2017 | Feb 28, 2018 | SAP_000.pdf |
| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| ID | Term |
|---|---|
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000591679 | cadazolid |
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
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| Vancomycin | Drug | Vancomycin 125 mg as oral capsules 4 times daily |
|
|
| Cadazolid-matching placebo | Drug | Placebo matching cadazolid and administered orally twice daily |
|
| Vancomycin-matching placebo | Drug | Placebo capsules matching vancomycin and administered orally 4 times per day |
|
| 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. | Up to Day 10 |
| 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. | Baseline to End of Treatment (10 days after starting study drug) + 2 days |
| Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) |
| 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. | Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) |
| 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). | Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days) |
| 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. | Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) |
| 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. | Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days) |
| Derived |
| Kleinman L, Talbot GH, Hunsche E, Schuler R, Nord CE. The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection. Value Health. 2018 Apr;21(4):441-448. doi: 10.1016/j.jval.2017.08.3017. Epub 2017 Nov 7. |
| Physician Decision |
|
| Lost to Follow-up |
|
| Sponsor Decision |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| CDAD episode type strata | CDAD episode type strata was defined as baseline stratification factor 'First occurrence' or 'First recurrence' of CDAD as recorded in the Interactive voice recognition system (IVRS) at the time of subject randomization. Number of subjects with first recurrence or first occurrence at randomization was assessed for each treatment group. | Count of Participants | Participants |
|
| Initial strain of Clostridium difficile | The strain of C. difficile at baseline was identified in the last stool sample collected up to treatment start date and with available C. difficile culture. Identification was done by polymerase chain reaction (PCR). The strains were categorized as hypervirulent strains (PCR ribotype 027, 078 or 244) or non-hypervirulent (other PCR ribotypes). The number of subjects with hypervirulent, non-hypervirulent strains at baseline was assessed for each treatment group. If PCR ribotype at baseline was not available, the subjects were classified as "unable to determine" | Count of Participants | Participants |
|
| CDAD severity at baseline | CDAD at baseline was considered as severe if the following criteria were met: maximum body temperature > 38.5 C, white blood cell counts > 15.0 x 10*9/L and rise in baseline serum creatinine > 50% compared to the level before CDAD diagnosis. Otherwise, it was considered as mild-moderate. The number of subjects with severe and mild-moderate CDAD at baseline was assessed for each treatment group. If any of the measurements required for derivation of severity was missing, the subjects were classified as "unable to determine" | Count of Participants | Participants |
|
| Cadazolid |
Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days |
| OG001 | Vancomycin | Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days |
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to Day 12 on average (end-of-treatment + 2 days) |
|
|
|
|
| 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). | 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. | Posted | Number | 95% Confidence Interval | Percentage of subjects | Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | KM estimate (% subjects with ROD) | Up to Day 10 |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | Scores on a scale | Baseline to End of Treatment (10 days after starting study drug) + 2 days |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Up to Day 12 on average (up to end-of-treatment + 2 to 4 days) |
|
|
|
|
| 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). | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days) |
|
|
|
|
| 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. | 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. | Posted | Number | 95% Confidence Interval | Percentage of participants | Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days) |
|
|
|
|
| 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. | Subjects from the modified intent-to-treat analysis set (mITT) with clinical cure | Posted | Number | 95% Confidence Interval | Percentage of participants | Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days) |
|
|
|
| 294 |
| 35 |
| 294 |
| 47 |
| 294 |
| EG001 | Vancomycin | oral vancomycin 125 mg 4 times per day (qid) for 10 days | 15 | 307 | 46 | 307 | 51 | 307 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 19.0 | Systematic Assessment |
|
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
| Bronchitis fungal | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Cardiac arrest | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cardiac failure acute | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cardiac failure chronic | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cardiopulmonary failure | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Chronic kidney disease | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Clostridium difficile infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
|
| Contrast media reaction | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Enterobacter sepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Enterococcal bacteraemia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Enterocolitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Enterocolitis haemorrhagic | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Escherichia bacteraemia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Escherichia test positive | Investigations | MedDRA 19.0 | Systematic Assessment |
|
| Escherichia urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Haematoma infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Hepatic encephalopathy | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Herpes simplex hepatitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
|
| Hypovolaemic shock | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Infectious pleural effusion | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Ischaemic stroke | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Liver injury | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Meningitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Multiple organ dysfunction syndrome | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
|
| Peripheral embolism | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
|
| Peripheral ischaemia | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Pneumonia klebsiella | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Porphyria acute | Congenital, familial and genetic disorders | MedDRA 19.0 | Systematic Assessment |
|
| Post procedural haematoma | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
|
| Pseudomembranous colitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Pulmonary sepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
|
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
|
| Renal cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Renal tubular necrosis | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
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| Supraventricular tachycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
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| Transplant abscess | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Transplant rejection | Immune system disorders | MedDRA 19.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Urinary tract infection bacterial | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Ventricular tachycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
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Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.
| D000602 |
| Amino Acids, Peptides, and Proteins |
| Day 3 |
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| Day 4 |
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| Day 5 |
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| Day 6 |
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| Day 7 |
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| Day 8 |
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| Day 9 |
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| Day 10 |
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| Other symptoms |
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| Comparison of the abdominal symptoms domain scores | ANOVA | ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12. | 0.7833 | Two-sided 5% alpha level was used | Least Square Mean difference | 0.025 | 2-Sided | 95 | -0.15 | 0.20 | The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements | Superiority |
| Comparison of the other symptoms domain scores | ANOVA | ANOVA model for repeated measurements was fitted using all values from Day 1 (baseline) to Day 12. | 0.4145 | Two-sided 5% alpha level was used | Least Square Mean difference | 0.061 | 2-Sided | 95 | -0.09 | 0.21 | The Least Square Means of the treatments differences for the changes from baseline at Day 3 were obtained using estimate statements | Superiority |