Comparison of Cadazolid Versus Vancomycin in Children With Clostridium Difficile-associated Diarrhea (CDAD)

Clostridium Difficile Infection Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03105479
• Other study ID #: AC-061A303
• Secondary ID: 2015-004805-17
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: April 14, 2017
• Est. completion date: April 17, 2018

Study information

• Verified date: March 2019
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: April 17, 2018
• Est. primary completion date: April 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Clostridium Difficile Infection
• Clostridium Infections
• Diarrhea

Intervention

Drug:
• Cadazolid
Granules for oral suspension to be administered twice daily
• Vancomycin capsule
Capsule containing 125 mg of vancomycin to be administered orally 4 times a day
• Vancomycin solution
Vancomycin powder to be administered as oral solution at a dose of 40 mg/kg/day, 3 to 4 times a day

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel - Kinderziekenhuis	Jette
Canada	Infection Prevention & Control, AGW5 Foothills Medical Center 1403 29th Street N.W.	Calgary
Czechia	FN Brno	Brno
Hungary	Egyesített Szent István és Szent László Kórház - Rendelointézet / Gyermekinfektológiai Osztály	Budapest
Hungary	Pándy Kálmán Megyei Kórház	Gyula
Italy	Ospedale Buzzi	Milano
Italy	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu	Roma
Poland	Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza	Bydgoszcz
Poland	Specjalistyczny Zespól Opieki Zdrowotnej nad Matka i Dzieckiem	Poznan
Poland	Gabinet Lekarski Bartosz Korczowski	Rzeszow
Poland	Klinika Gastroenterologii, Hepatologii, Zaburzen Odzywiania i Pediatrii, Instytut "Pomnik - Centrum Zdrowia Dziecka"	Warsaw
Romania	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
Spain	Hospital Sant Joan de Déu, Esplugues	Barcelona
Spain	Hospital Universitario Infantil LA PAZ	Madrid
United States	University of Chicago, Dept. Of Medicine	Chicago	Illinois
United States	Texas Children's Hospital Feigin Cente	Houston	Texas
United States	Snake River Research, PLLC	Idaho Falls	Idaho
United States	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	SUNY Upstate Medical University - Upstate Golisano Children's Hospital (GCH) - Pediatric Designated AIDS Center	Syracuse	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Hungary,  Italy,  Poland,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day 10 (End of Treatment) + 2 days
Primary	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.	Day 10 (End of Treatment)
Primary	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.	Day 10 (End of Treatment)
Primary	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.	Day 10 (End of Treatment)
Primary	Fecal Concentrations of Cadazolid During Part A	A fecal sample is collected as the end-of-treatment visit in all participants in Part A.	Day 10 (End of Treatment)
Secondary	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).	Day 10 (End of Treatment) + 2 days
Secondary	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).	Day 40 (on average)
Secondary	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.	Day 40 (on average)
Secondary	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)	Day 40 (on average)
Secondary	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	Day 10
Secondary	Adverse Events Leading to Premature Discontinuation of Study Treatment	Number of participants who prematurely discontinued the study treatment due to an adverse event	Up to Day 10
Secondary	Marked Abnormalities in Clinical Laboratory Parameters	Number of participants with any marked abnormalities in laboratory parameters up to 7 days after end of treatment	Day 17 (on average)
Secondary	Marked Abnormalities in Vital Signs	Number of subjects with any treatment-emergent abnormalities in vital signs (up to 7 days after end of treatment)	Day 17 (on average)
Secondary	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.	Day 17 (on average)