Efficacy and Safety of Cadazolid Versus Vancomycin in Subjects With Clostridium Difficile - Associated Diarrhea

Browse trials for

• Clostridium Infections 310
• Diarrhea 852

Keywords

• Post-antibiotic diarrhea
• Clostridium difficile infection

Clostridium Infections

310 studies on the registry are indexed under Clostridium Infections; 50 are open to participants now.

This study's enrollment of 632 is above the median of 65 across 233 interventional studies indexed under Clostridium Infections.

Lead sponsor

Actelion is the lead sponsor of 140 studies on the registry; 1 is open to participants now.

Of its 27 completed or terminated interventional studies of FDA-regulated products, 24 (89%) have results posted.

Study arms

• Experimental
  Cadazolid

  Subjects receive oral cadazolid 250 mg twice daily (bid) and oral vancomycin-matching placebo 4 times per day (qid) for 10 days

  Drug: Cadazolid · Drug: Vancomycin-matching placebo

• Active comparator
  Vancomycin

  Subjects receive oral vancomycin 125 mg qid and oral cadazolid-matching placebo bid for 10 days

  Drug: Vancomycin · Drug: Cadazolid-matching placebo

Interventions

• DrugCadazolid

  Cadazolid 250 mg as oral suspension twice daily.

  Also known as: ACT-179811

• DrugVancomycin

  Vancomycin 125 mg as oral capsules 4 times daily.

  Also known as: Vancocin

• DrugCadazolid-matching placebo

  Placebo matching cadazolid and administered orally twice daily

• DrugVancomycin-matching placebo

  Placebo capsules matching vancomycin and administered orally 4 times per day

Primary outcomes

1. Clinical Cure Rate (CCR) in the Modified Intent-to-treat 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 modified intent-to-treat set (mITT) are reported below.

   Time frame: Up to Day 12 on average (end-of-treatment + 2 days)

2. 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)

Secondary outcomes

1. 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)

2. Kaplan-Meier Estimates for Resolution of Diarrhea

   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

3. 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. The least squares means (LSM) are computed on the scores.

   Time frame: Day 1 (baseline) and Day 3

Other outcomes

1. 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)

2. 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)

3. 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)

4. 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)

5. 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)

Baseline characteristics

Publications

• 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. PubMed 30709665 ↗
• 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. PubMed 29680101 ↗

Study documents

• Study protocol · Oct 22, 2015
• Statistical analysis plan · May 19, 2017

Documents are hosted by the registry — open the source record to download them.