Comparison of Cadazolid Versus Vancomycin in Children With Clostridium Difficile-associated Diarrhea (CDAD)
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| ClinicalTrials.gov Identifier: NCT03105479 |
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Recruitment Status :
Terminated
(Study suspended in October 2017 and terminated April 17, 2018 after decision to discontinue the study drug development)
First Posted : April 10, 2017
Results First Posted : April 3, 2019
Last Update Posted : April 3, 2019
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Sponsor:
Actelion
Information provided by (Responsible Party):
Actelion
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Brief Summary:
Cadazolid has demonstrated activity against a bacteria named Clostridium difficile in animal studies. The results of a first study conducted in adult patients have suggested efficacy of the new antibiotic, cadazolid, in the treatment of diarrhea caused by this bacteria. This is the first study of cadazolid in children. The overall purpose of this study is to provide reassurance on the safety and efficacy of cadazolid in children suffering from infection due to Clostridium difficile.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Clostridium Difficile Infection | Drug: Cadazolid Drug: Vancomycin capsule Drug: Vancomycin solution | Phase 2 Phase 3 |
This multicenter, study will be run into two parts. Both parts will be run in consecutive age cohorts, starting from the oldest age categories(12 to < 18 years old) to the youngest (birth to < 3 months).
- Part A is an open-label, dose finding part to be conducted in at least 24 subjects.
- Part B follows a randomized, assessor-blinded, parallel-group design with vancomycin used as an active comparator. Part B will be conducted in about 176 children.
In both parts, the treatment period will be 10 days and will be followed by a Follow-up period of 28-32 days.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Masking Description: | Assessor masking in Part B only (no masking in Part A) |
| Primary Purpose: | Treatment |
| Official Title: | A Prospective, Multicenter Study to Investigate the Pharmacokinetics, Safety, and Efficacy of Cadazolid Versus Vancomycin in Pediatric Subjects With Clostridium Difficile-associated Diarrhea |
| Actual Study Start Date : | April 14, 2017 |
| Actual Primary Completion Date : | April 17, 2018 |
| Actual Study Completion Date : | April 17, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part A / Cohort A
Subjects from 12 years to 18 years old (exclusive) will receive cadazolid 500 mg per day for 10 days. The dose may be adjusted based on the pharmacokinetic (PK) and safety data reviewed for the first 3 subjects.
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Drug: Cadazolid
Granules for oral suspension to be administered twice daily
Other Name: ACT-179811 |
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Experimental: Part A / Cohort B
Subjects from 6 years to 12 years old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort A reviewed by the Independent Data Monitoring Committee (IDMC).
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Drug: Cadazolid
Granules for oral suspension to be administered twice daily
Other Name: ACT-179811 |
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Experimental: Part A / Cohort C
Subjects from 2 years to 6 years old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort B reviewed by the IDMC.
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Drug: Cadazolid
Granules for oral suspension to be administered twice daily
Other Name: ACT-179811 |
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Experimental: Part A/ Cohort D
Subjects from 3 months to 2 years old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort C reviewed by the IDMC.
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Drug: Cadazolid
Granules for oral suspension to be administered twice daily
Other Name: ACT-179811 |
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Experimental: Part A/ Cohort E
Subjects from birth to 3 months old (exclusive) will receive cadazolid for 10 days. The dose will depend on the PK and safety data from cohort D reviewed by the IDMC.
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Drug: Cadazolid
Granules for oral suspension to be administered twice daily
Other Name: ACT-179811 |
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Experimental: Part B / Cadazolid
Subjects from birth to 18 years old (exclusive) will receive cadazolid for 10 days, at the dose defined in the corresponding age cohort in Part A.
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Drug: Cadazolid
Granules for oral suspension to be administered twice daily
Other Name: ACT-179811 |
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Active Comparator: Part B / Vancomycin
Subjects from birth to 18 years old (exclusive) will receive vancomycin capsule (for subjects able to swallow) or vancomycin solution (for the others) during 10 days .
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Drug: Vancomycin capsule
Capsule containing 125 mg of vancomycin to be administered orally 4 times a day Drug: Vancomycin solution Vancomycin powder to be administered as oral solution at a dose of 40 mg/kg/day, 3 to 4 times a day |
Primary Outcome Measures :
- Clinical Cure Rate During Part B [ Time Frame: Day 10 (End of Treatment) + 2 days ]This is the percentage of participants in part B reported as with a clinical cure. Clinical Cure is defined as: • <3 unformed bowel movement (UBM) per day (or no water diarrhea if subjects < 2 years of age), for at least 2 consecutive days between first dose of study treatment up to end of treatment (EOT) (inclusive) AND • Subject remains well up to EOT + 2 days (inclusive) based on investigator judgment AND • No need for additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) between first dose of study treatment up to EOT + 2 days (inclusive). percentage of subjects with a clinical cure
- Maximal Plasma Concentration (Cmax) of Cadazolid During Part A [ Time Frame: Day 10 (End of Treatment) ]Blood samples are collected at different timepoints on Day 10 for the determination of cadazolid Cmax after 10 days of treatment.
- Time to Reach Cmax (Tmax) of Cadazolid During Part A [ Time Frame: Day 10 (End of Treatment) ]Blood samples are collected at different timepoints to determine the time when the maximal plasma concentration of cadazolid is reached.
- Area Under the Plasma Concentration Time Curve (AUC) of Cadazolid During Part A [ Time Frame: Day 10 (End of Treatment) ]Blood samples are collected at different timepoints for the determination of the cadazolid AUC over one dosing interval (0-12h) on Day 10.
- Fecal Concentrations of Cadazolid During Part A [ Time Frame: Day 10 (End of Treatment) ]A fecal sample is collected as the end-of-treatment visit in all participants in Part A.
Secondary Outcome Measures :
- Clinical Cure Rate During Part A [ Time Frame: Day 10 (End of Treatment) + 2 days ]This is the percentage of participants in Part A reported as with a clinical cure. Clinical Cure is defined as: • <3 unformed bowel movement (UBM) per day (or no water diarrhea if subjects < 2 years of age), for at least 2 consecutive days between first dose of study treatment up to end of treatment (EOT) (inclusive) AND • Subject remains well up to EOT + 2 days (inclusive) based on investigator judgment AND • No need for additional antimicrobial treatment active against Clostridium difficile-associated diarrhea (CDAD) between first dose of study treatment up to EOT + 2 days (inclusive).
- Sustained Clinical Cure Rate During Part A and Part B [ Time Frame: Day 40 (on average) ]This is the percentage of participants in Parts A and B reported as with sustained clinical cure. Sustained clinical cure is defined as • Clinical Cure and no Recurrence until 30 days after the last study drug intake (end of study).
- Recurrence Rate During Part A and Part B [ Time Frame: Day 40 (on average) ]This is the percentage of participants in Parts A and B assessed as having a recurrence out of subjects meeting the criteria for Clinical Cure. Recurrence is defined as: • Clinical Cure AND New episode of diarrhea with ≥ 3 UBMs (or watery diarrhea if subject < 2 years) on any day between EOT + 3 days and end of study AND • Stool test showing positive C. difficile (as defined in Inclusion Criterion 4), AND •Antimicrobial treatment active against CDAD started between EOT + 3 days and end of study.
- Time to Recurrence in Part B [ Time Frame: Day 40 (on average) ]This it the time (in days) elapsed between the last dose of study drug and the onset day of new episode of diarrhea reported as Kaplan-Meier estimates (KM estimates)
- Time to Resolution of Diarrhea in Part B [ Time Frame: Day 10 ]This is the time (in days) elapsed between the first dose of study treatment and the resolution of diarrhea and reported as Kaplan-Meier estimates (KM estimates). The date of resolution of Diarrhea (ROD) is defined as the date of the first day of the 2 consecutive days on treatment with < 3 UBM (or no watery diarrhea for subjects < 2 years of age). Time to ROD is the time (in days) elapsed between the first dose of study treatment and the ROD
- Adverse Events Leading to Premature Discontinuation of Study Treatment [ Time Frame: Up to Day 10 ]Number of participants who prematurely discontinued the study treatment due to an adverse event
- Marked Abnormalities in Clinical Laboratory Parameters [ Time Frame: Day 17 (on average) ]Number of participants with any marked abnormalities in laboratory parameters up to 7 days after end of treatment
- Marked Abnormalities in Vital Signs [ Time Frame: Day 17 (on average) ]Number of subjects with any treatment-emergent abnormalities in vital signs (up to 7 days after end of treatment)
- Treatment-emergent Adverse Events (TEAES) [ Time Frame: Day 17 (on average) ]Number of subjects with any TEAEs. A TEAE is any adverse event temporally associated with the use of study treatment (from study treatment initiation until 7 days after study treatment discontinuation) whether or not considered by the investigator as related to study treatment.
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| Ages Eligible for Study: | up to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Signed informed consent by parents or legally authorized representatives (LAR) and assent by the child according to local requirements prior to initiation of any study-mandated procedure.
- Male or female from birth to < 18 years of age, diagnosed with Clostridium Difficile-associated diarrhea (CDAD).
- Females of childbearing potential must have a negative pregnancy test at screening and must agree to use an adequate and reliable method of contraception.
Key Exclusion Criteria:
- Positive Rotavirus test for subjects < 5 years.
- Fulminant or life-threatening CDAD.
- More than one previous episode of CDAD in the 3 month period prior to enrollment / randomization.
- Antimicrobial treatment active against CDAD administered within 24 h prior to screening except for metronidazole treatment failures (MTF).
- Subjects with body weight < 3 kg.
- Inflammatory bowel disease, chronic abdominal pain, or chronic diarrhea of any etiology.
- Fecal microbiota transplant (FMT), immunoglobulin therapy, or any investigational drug to prevent or treat CDAD within 1 month period (or 5 half-lives in case of investigational drug, whichever is longer) prior to enrollment / randomization.
- Monoclonal antibodies against C. difficile within 6 months prior to enrollment / randomization.
- Previous vaccination against C. difficile.
- Known mental disorders.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study, or compliance with the protocol.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03105479
Locations
Show 20 study locations
Sponsors and Collaborators
Actelion
Study Documents (Full-Text)
Documents provided by Actelion:
Documents provided by Actelion:
Study Protocol [PDF] March 1, 2017
No Statistical Analysis Plan (SAP) exists for this study.
| Responsible Party: | Actelion |
| ClinicalTrials.gov Identifier: | NCT03105479 |
| Other Study ID Numbers: |
AC-061A303 2015-004805-17 ( EudraCT Number ) |
| First Posted: | April 10, 2017 Key Record Dates |
| Results First Posted: | April 3, 2019 |
| Last Update Posted: | April 3, 2019 |
| Last Verified: | March 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Actelion:
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vancomycin children cadazolid clostridium difficile associated diarrhea |
Additional relevant MeSH terms:
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Clostridium Infections Diarrhea Signs and Symptoms, Digestive Gram-Positive Bacterial Infections Bacterial Infections |
Bacterial Infections and Mycoses Infections Vancomycin Anti-Bacterial Agents Anti-Infective Agents |