Clinical trial NCT03105479: 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
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Clostridium Difficile Infection
Keywords: vancomycin
children
cadazolid
clostridium difficile associated diarrhea
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2017-04-10
Enrollment: 1
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical Cure Rate During Part B
timeFrame: Day 10 (End of Treatment) + 2 days
measure: Maximal Plasma Concentration (Cmax) of Cadazolid During Part A
timeFrame: Day 10 (End of Treatment)
measure: Time to Reach Cmax (Tmax) of Cadazolid During Part A
timeFrame: Day 10 (End of Treatment)
measure: Area Under the Plasma Concentration Time Curve (AUC) of Cadazolid During Part A
timeFrame: Day 10 (End of Treatment)
measure: Fecal Concentrations of Cadazolid During Part A
timeFrame: Day 10 (End of Treatment)
Secondary outcomes:
measure: Clinical Cure Rate During Part A
timeFrame: Day 10 (End of Treatment) + 2 days
measure: Sustained Clinical Cure Rate During Part A and Part B
timeFrame: Day 40 (on average)
measure: Recurrence Rate During Part A and Part B
timeFrame: Day 40 (on average)
measure: Time to Recurrence in Part B
timeFrame: Day 40 (on average)
measure: Time to Resolution of Diarrhea in Part B
timeFrame: Day 10
measure: Adverse Events Leading to Premature Discontinuation of Study Treatment
timeFrame: Up to Day 10
measure: Marked Abnormalities in Clinical Laboratory Parameters
timeFrame: Day 17 (on average)
measure: Marked Abnormalities in Vital Signs
timeFrame: Day 17 (on average)
measure: Treatment-emergent Adverse Events (TEAES)
timeFrame: Day 17 (on average)
Other outcomes:
Locations:
city: Idaho Falls
country: United States
facility: Snake River Research, PLLC
state: Idaho
city: Chicago
country: United States
facility: University of Chicago, Dept. Of Medicine
state: Illinois
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Syracuse
country: United States
facility: SUNY Upstate Medical University - Upstate Golisano Children's Hospital (GCH) - Pediatric Designated AIDS Center
state: Ohio
city: Houston
country: United States
facility: Texas Children's Hospital Feigin Cente
state: Texas
city: Jette
country: Belgium
facility: Universitair Ziekenhuis Brussel - Kinderziekenhuis
city: Calgary
country: Canada
facility: Infection Prevention & Control, AGW5 Foothills Medical Center 1403 29th Street N.W.
city: Brno
country: Czechia
facility: FN Brno
city: Budapest
country: Hungary
facility: Egyesített Szent István és Szent László Kórház - Rendelőintézet / Gyermekinfektológiai Osztály
city: Gyula
country: Hungary
facility: Pándy Kálmán Megyei Kórház
city: Milano
country: Italy
facility: Ospedale Buzzi
city: Roma
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza
city: Poznan
country: Poland
facility: Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem
city: Rzeszow
country: Poland
facility: Gabinet Lekarski Bartosz Korczowski
city: Warsaw
country: Poland
facility: Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii, Instytut "Pomnik - Centrum Zdrowia Dziecka"
city: Bucharest
country: Romania
facility: Institutul National De Boli Infectioase "Prof. Dr. Matei Bals", sectia IX pediatrie
city: Iasi
country: Romania
facility: Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi, Clinica de Boli Infectioase I,
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu, Esplugues
city: Madrid
country: Spain
facility: Hospital Universitario Infantil LA PAZ
Study officials:
References: