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

Actelion Pharmaceuticals

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Clostridium Difficile Infection

Treatments: Drug: Vancomycin solution; Drug: Cadazolid; Drug: Vancomycin capsule

Study type: Interventional

Funder types: Industry

Identifiers

NCT03105479

2015-004805-17 (EudraCT Number)

AC-061A303

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1 participants in 7 patient groups

Part A / Cohort A

Experimental group

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.

Treatment:

Drug: Cadazolid

Part A / Cohort B

Experimental group

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).

Treatment:

Drug: Cadazolid

Part A / Cohort C

Experimental group

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.

Treatment:

Drug: Cadazolid

Part A/ Cohort D

Experimental group

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.

Treatment:

Drug: Cadazolid

Part A/ Cohort E

Experimental group

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.

Treatment:

Drug: Cadazolid

Part B / Cadazolid

Experimental group

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.

Treatment:

Drug: Cadazolid

Part B / Vancomycin

Active Comparator group

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 .

Treatment:

Drug: Vancomycin capsule

Drug: Vancomycin solution