Back to resultsComparison of Cadazolid Versus Vancomycin in Children With Clostridium Difficile-associated Diarrhea (CDAD)
Primary Purpose
Clostridium Difficile Infection
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cadazolid
Vancomycin capsule
Vancomycin solution
Sponsored by
About this trial
This is an interventional treatment trial for Clostridium Difficile Infection focused on measuring vancomycin, children, cadazolid, clostridium difficile associated diarrhea
Eligibility 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.
Sites / Locations
- Snake River Research, PLLC
- University of Chicago, Dept. Of Medicine
- Louisiana State University Health Sciences Center - Shreveport
- SUNY Upstate Medical University - Upstate Golisano Children's Hospital (GCH) - Pediatric Designated AIDS Center
- Texas Children's Hospital Feigin Cente
- Universitair Ziekenhuis Brussel - Kinderziekenhuis
- Infection Prevention & Control, AGW5 Foothills Medical Center 1403 29th Street N.W.
- FN Brno
- Egyesített Szent István és Szent László Kórház - Rendelőintézet / Gyermekinfektológiai Osztály
- Pándy Kálmán Megyei Kórház
- Ospedale Buzzi
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu
- Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza
- Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem
- Gabinet Lekarski Bartosz Korczowski
- Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii, Instytut "Pomnik - Centrum Zdrowia Dziecka"
- Institutul National De Boli Infectioase "Prof. Dr. Matei Bals", sectia IX pediatrie
- Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi, Clinica de Boli Infectioase I,
- Hospital Sant Joan de Déu, Esplugues
- Hospital Universitario Infantil LA PAZ
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Part A / Cohort A
Part A / Cohort B
Part A / Cohort C
Part A/ Cohort D
Part A/ Cohort E
Part B / Cadazolid
Part B / Vancomycin
Arm Description
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.
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).
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.
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.
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.
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.
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 .
Outcomes
Primary Outcome Measures
Clinical Cure Rate During Part B
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
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
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
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
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
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
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
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
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
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
Number of participants who prematurely discontinued the study treatment due to an adverse event
Marked Abnormalities in Clinical Laboratory Parameters
Number of participants with any marked abnormalities in laboratory parameters up to 7 days after end of treatment
Marked Abnormalities in Vital Signs
Number of subjects with any treatment-emergent abnormalities in vital signs (up to 7 days after end of treatment)
Treatment-emergent Adverse Events (TEAES)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03105479
Brief Title
Comparison of Cadazolid Versus Vancomycin in Children With Clostridium Difficile-associated Diarrhea (CDAD)
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
Study suspended in October 2017 and terminated April 17, 2018 after decision to discontinue the study drug development
Study Start Date
April 14, 2017 (Actual)
Primary Completion Date
April 17, 2018 (Actual)
Study Completion Date
April 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection
Keywords
vancomycin, children, cadazolid, clostridium difficile associated diarrhea
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Assessor masking in Part B only (no masking in Part A)
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A / Cohort A
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A / Cohort B
Arm Type
Experimental
Arm Description
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).
Arm Title
Part A / Cohort C
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A/ Cohort D
Arm Type
Experimental
Arm Description
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.
Arm Title
Part A/ Cohort E
Arm Type
Experimental
Arm Description
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.
Arm Title
Part B / Cadazolid
Arm Type
Experimental
Arm Description
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.
Arm Title
Part B / Vancomycin
Arm Type
Active Comparator
Arm Description
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 .
Intervention Type
Drug
Intervention Name(s)
Cadazolid
Other Intervention Name(s)
ACT-179811
Intervention Description
Granules for oral suspension to be administered twice daily
Intervention Type
Drug
Intervention Name(s)
Vancomycin capsule
Intervention Description
Capsule containing 125 mg of vancomycin to be administered orally 4 times a day
Intervention Type
Drug
Intervention Name(s)
Vancomycin solution
Intervention Description
Vancomycin powder to be administered as oral solution at a dose of 40 mg/kg/day, 3 to 4 times a day
Primary Outcome Measure Information:
Title
Clinical Cure Rate During Part B
Description
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
Time Frame
Day 10 (End of Treatment) + 2 days
Title
Maximal Plasma Concentration (Cmax) of Cadazolid During Part A
Description
Blood samples are collected at different timepoints on Day 10 for the determination of cadazolid Cmax after 10 days of treatment.
Time Frame
Day 10 (End of Treatment)
Title
Time to Reach Cmax (Tmax) of Cadazolid During Part A
Description
Blood samples are collected at different timepoints to determine the time when the maximal plasma concentration of cadazolid is reached.
Time Frame
Day 10 (End of Treatment)
Title
Area Under the Plasma Concentration Time Curve (AUC) of Cadazolid During Part A
Description
Blood samples are collected at different timepoints for the determination of the cadazolid AUC over one dosing interval (0-12h) on Day 10.
Time Frame
Day 10 (End of Treatment)
Title
Fecal Concentrations of Cadazolid During Part A
Description
A fecal sample is collected as the end-of-treatment visit in all participants in Part A.
Time Frame
Day 10 (End of Treatment)
Secondary Outcome Measure Information:
Title
Clinical Cure Rate During Part A
Description
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).
Time Frame
Day 10 (End of Treatment) + 2 days
Title
Sustained Clinical Cure Rate During Part A and Part B
Description
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).
Time Frame
Day 40 (on average)
Title
Recurrence Rate During Part A and Part B
Description
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 Frame
Day 40 (on average)
Title
Time to Recurrence in Part B
Description
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 Frame
Day 40 (on average)
Title
Time to Resolution of Diarrhea in Part B
Description
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
Time Frame
Day 10
Title
Adverse Events Leading to Premature Discontinuation of Study Treatment
Description
Number of participants who prematurely discontinued the study treatment due to an adverse event
Time Frame
Up to Day 10
Title
Marked Abnormalities in Clinical Laboratory Parameters
Description
Number of participants with any marked abnormalities in laboratory parameters up to 7 days after end of treatment
Time Frame
Day 17 (on average)
Title
Marked Abnormalities in Vital Signs
Description
Number of subjects with any treatment-emergent abnormalities in vital signs (up to 7 days after end of treatment)
Time Frame
Day 17 (on average)
Title
Treatment-emergent Adverse Events (TEAES)
Description
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.
Time Frame
Day 17 (on average)
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Snake River Research, PLLC
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
University of Chicago, Dept. Of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Louisiana State University Health Sciences Center - Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
SUNY Upstate Medical University - Upstate Golisano Children's Hospital (GCH) - Pediatric Designated AIDS Center
City
Syracuse
State/Province
Ohio
ZIP/Postal Code
13210
Country
United States
Facility Name
Texas Children's Hospital Feigin Cente
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Universitair Ziekenhuis Brussel - Kinderziekenhuis
City
Jette
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Infection Prevention & Control, AGW5 Foothills Medical Center 1403 29th Street N.W.
City
Calgary
ZIP/Postal Code
T2N 2T9
Country
Canada
Facility Name
FN Brno
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
Egyesített Szent István és Szent László Kórház - Rendelőintézet / Gyermekinfektológiai Osztály
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
Pándy Kálmán Megyei Kórház
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Ospedale Buzzi
City
Milano
ZIP/Postal Code
20154
Country
Italy
Facility Name
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza
City
Bydgoszcz
ZIP/Postal Code
85-030
Country
Poland
Facility Name
Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem
City
Poznan
ZIP/Postal Code
61-734
Country
Poland
Facility Name
Gabinet Lekarski Bartosz Korczowski
City
Rzeszow
ZIP/Postal Code
35-302
Country
Poland
Facility Name
Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii, Instytut "Pomnik - Centrum Zdrowia Dziecka"
City
Warsaw
ZIP/Postal Code
04-730
Country
Poland
Facility Name
Institutul National De Boli Infectioase "Prof. Dr. Matei Bals", sectia IX pediatrie
City
Bucharest
ZIP/Postal Code
21105
Country
Romania
Facility Name
Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi, Clinica de Boli Infectioase I,
City
Iasi
ZIP/Postal Code
700116
Country
Romania
Facility Name
Hospital Sant Joan de Déu, Esplugues
City
Barcelona
ZIP/Postal Code
8950
Country
Spain
Facility Name
Hospital Universitario Infantil LA PAZ
City
Madrid
ZIP/Postal Code
28046
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Comparison of Cadazolid Versus Vancomycin in Children With Clostridium Difficile-associated Diarrhea (CDAD)
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