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

NCT01983683 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: AC-061A302
• Study Type: interventional
• Target: 631
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD).

Conditions

Clostridium Difficile Infection

Keywords

Clostridium difficile infection; Post-antibiotic diarrhea

Outcome Measures

Primary Outcomes (2)

• 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)

Secondary Outcomes (3)

• 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)

• Kaplan-Meier Estimates for Resolution of Diarrhea (ROD)

  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

  Baseline to End of Treatment (10 days after starting study drug) + 2 days

Other Outcomes (5)

• 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)

• 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)

• 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)

Study Arms (2)

Cadazolid

EXPERIMENTAL

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

Vancomycin

ACTIVE COMPARATOR

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

Drug: Vancomycin; Drug: Cadazolid-matching placebo

Interventions

Cadazolid DRUG

Cadazolid 250 mg as oral suspension twice daily.

Also known as: ACT-179811

Cadazolid

Vancomycin DRUG

Vancomycin 125 mg as oral capsules 4 times daily

Also known as: Vancocin

Vancomycin

Cadazolid-matching placebo DRUG

Placebo matching cadazolid and administered orally twice daily

Vancomycin

Vancomycin-matching placebo DRUG

Placebo capsules matching vancomycin and administered orally 4 times per day

Cadazolid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Actelion: lead

Related Publications (2)

• 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.

  PMID: 30709665 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.

  PMID: 29680101 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Interventions

cadazolid; Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: clinical trial disclosure desk
• Organization: Actelion Pharmaceuticals Ltd

clinical-trials-disclosure@its.jnj.com

0041615656565

Study Officials

• Anne Claire Marrast, MD

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2013
• First Posted: November 14, 2013
• Study Start: December 12, 2013
• Primary Completion: March 9, 2017
• Study Completion: May 2, 2017
• Last Updated: February 4, 2025
• Results First Posted: April 13, 2018

Record last verified: 2025-01