Comparison of Cadazolid Versus Vancomycin in Children With Clostridium Difficile-associated Diarrhea (CDAD)
- Conditions
- Clostridium Difficile Infection
- Interventions
- Registration Number
- NCT03105479
- Lead Sponsor
- Actelion
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B / Vancomycin Vancomycin capsule 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 . Part A / Cohort C Cadazolid 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. Part B / Vancomycin Vancomycin solution 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 . Part A / Cohort A Cadazolid 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. Part A / Cohort B Cadazolid 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). Part A/ Cohort D Cadazolid 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. Part A/ Cohort E Cadazolid 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. Part B / Cadazolid 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.
- Primary Outcome Measures
Name Time Method Fecal Concentrations of Cadazolid During Part A Day 10 (End of Treatment) A fecal sample is collected as the end-of-treatment visit in all participants in Part A.
Maximal Plasma Concentration (Cmax) of Cadazolid During Part A 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.
Area Under the Plasma Concentration Time Curve (AUC) of Cadazolid During Part A 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.
Time to Reach Cmax (Tmax) of Cadazolid During Part A 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.
Clinical Cure Rate During Part B 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
- Secondary Outcome Measures
Name Time Method Clinical Cure Rate During Part A 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).
Time to Recurrence in Part B 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)
Sustained Clinical Cure Rate During Part A and Part B 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).
Adverse Events Leading to Premature Discontinuation of Study Treatment Up to Day 10 Number of participants who prematurely discontinued the study treatment due to an adverse event
Marked Abnormalities in Vital Signs 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) 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.
Recurrence Rate During Part A and Part B 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 Resolution of Diarrhea in Part B 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
Marked Abnormalities in Clinical Laboratory Parameters Day 17 (on average) Number of participants with any marked abnormalities in laboratory parameters up to 7 days after end of treatment
Trial Locations
- Locations (20)
University of Chicago, Dept. Of Medicine
🇺🇸Chicago, Illinois, United States
SUNY Upstate Medical University - Upstate Golisano Children's Hospital (GCH) - Pediatric Designated AIDS Center
🇺🇸Syracuse, Ohio, United States
Hospital Sant Joan de Déu, Esplugues
🇪🇸Barcelona, Spain
Texas Children's Hospital Feigin Cente
🇺🇸Houston, Texas, United States
Hospital Universitario Infantil LA PAZ
🇪🇸Madrid, Spain
FN Brno
🇨🇿Brno, Czechia
Snake River Research, PLLC
🇺🇸Idaho Falls, Idaho, United States
Infection Prevention & Control, AGW5 Foothills Medical Center 1403 29th Street N.W.
🇨🇦Calgary, Canada
Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii, Instytut "Pomnik - Centrum Zdrowia Dziecka"
🇵🇱Warsaw, Poland
Ospedale Buzzi
🇮🇹Milano, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu
🇮🇹Roma, Italy
Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza
🇵🇱Bydgoszcz, Poland
Louisiana State University Health Sciences Center - Shreveport
🇺🇸Shreveport, Louisiana, United States
Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem
🇵🇱Poznan, Poland
Gabinet Lekarski Bartosz Korczowski
🇵🇱Rzeszow, Poland
Egyesített Szent István és Szent László Kórház - Rendelőintézet / Gyermekinfektológiai Osztály
🇭🇺Budapest, Hungary
Universitair Ziekenhuis Brussel - Kinderziekenhuis
🇧🇪Jette, Belgium
Pándy Kálmán Megyei Kórház
🇭🇺Gyula, Hungary
Institutul National De Boli Infectioase "Prof. Dr. Matei Bals", sectia IX pediatrie
🇷🇴Bucharest, Romania
Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi, Clinica de Boli Infectioase I,
🇷🇴Iasi, Romania