Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2015-004805-17 | EudraCT Number |
Not provided
Not provided
Not provided
Study suspended in October 2017 and terminated April 17, 2018 after decision to discontinue the study drug development
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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).
In both parts, the treatment period will be 10 days and will be followed by a Follow-up period of 28-32 days.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A / Cohort A | Experimental | 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 | Experimental | 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 C | Experimental | 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 A/ Cohort D | Experimental | 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 | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cadazolid | Drug | Granules for oral suspension to be administered twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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) |
| 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) |
| 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) |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
Not provided
Key Inclusion Criteria:
Key Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Snake River Research, PLLC | Idaho Falls | Idaho | 83404 | United States | ||
| University of Chicago, Dept. Of Medicine |
Not provided
Due to early termination of the study after sponsor's decision to discontinue the development of cadazolid, only one patient was enrolled at one site in the US.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Part A / Cohort A | Subjects from 12 years to 18 years old (exclusive) are to be treated with cadazolid 250 mg twice daily for 10 days. The dose may be adjusted based on the pharmacokinetic (PK) and safety data reviewed for the first 3 subjects. |
| FG001 | Part A / Cohort B |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 1, 2017 | Mar 14, 2019 |
Not provided
Not provided
Not provided
Not provided
Assessor masking in Part B only (no masking in Part A)
|
| Part B / Cadazolid | Experimental | 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. |
|
| Part B / Vancomycin | Active Comparator | 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 . |
|
|
| Vancomycin capsule | Drug | Capsule containing 125 mg of vancomycin to be administered orally 4 times a day |
|
| Vancomycin solution | Drug | Vancomycin powder to be administered as oral solution at a dose of 40 mg/kg/day, 3 to 4 times a day |
|
| Day 10 (End of Treatment) + 2 days |
| 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) |
| 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) |
| 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) |
| 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 |
| 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 |
| 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) |
| 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) |
| 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) |
| Chicago |
| Illinois |
| 60637 |
| United States |
| Louisiana State University Health Sciences Center - Shreveport | Shreveport | Louisiana | 71103 | United States |
| SUNY Upstate Medical University - Upstate Golisano Children's Hospital (GCH) - Pediatric Designated AIDS Center | Syracuse | Ohio | 13210 | United States |
| Texas Children's Hospital Feigin Cente | Houston | Texas | 77030 | United States |
| Universitair Ziekenhuis Brussel - Kinderziekenhuis | Jette | 1090 | Belgium |
| Infection Prevention & Control, AGW5 Foothills Medical Center 1403 29th Street N.W. | Calgary | T2N 2T9 | Canada |
| FN Brno | Brno | 62500 | Czechia |
| EgyesÃtett Szent István és Szent László Kórház - RendelÅ‘intézet / Gyermekinfektológiai Osztály | Budapest | 1097 | Hungary |
| Pándy Kálmán Megyei Kórház | Gyula | 5700 | Hungary |
| Ospedale Buzzi | Milan | 20154 | Italy |
| Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu | Roma | 00165 | Italy |
| Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza | Bydgoszcz | 85-030 | Poland |
| Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem | Poznan | 61-734 | Poland |
| Gabinet Lekarski Bartosz Korczowski | Rzeszów | 35-302 | Poland |
| Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii, Instytut "Pomnik - Centrum Zdrowia Dziecka" | Warsaw | 04-730 | Poland |
| Institutul National De Boli Infectioase "Prof. Dr. Matei Bals", sectia IX pediatrie | Bucharest | 21105 | Romania |
| Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi, Clinica de Boli Infectioase I, | Iași | 700116 | Romania |
| Hospital Sant Joan de Déu, Esplugues | Barcelona | 8950 | Spain |
| Hospital Universitario Infantil LA PAZ | Madrid | 28046 | Spain |
Subjects from 6 years to 12 years old (exclusive) are to be treated with cadazolid for 10 days (dose determined based on the PK and safety data from cohort A reviewed by the Independent Data Monitoring Committee (IDMC)). |
| FG002 | Part A / Cohort C | Subjects from 2 years to 6 years old (exclusive) are to be treated with cadazolid for 10 days. (dose determined based on the PK and safety data from cohort B reviewed by the IDMC). |
| FG003 | Part A/ Cohort D | Subjects from 3 months to 2 years old (exclusive) are to be treated with cadazolid for 10 days (dose determined based on the PK and safety data from cohort B reviewed by the IDMC). |
| FG004 | Part A/ Cohort E | Subjects from birth to 3 months old (exclusive) are to be treated with cadazolid for 10 days (dose determined based on the PK and safety data from cohort B reviewed by the IDMC). . |
| FG005 | Part B / Cadazolid | Subjects from birth to 18 years old (exclusive) are to be treated with cadazolid for 10 days, at the dose defined in the corresponding age cohort in Part A. |
| FG006 | Part B / Vancomycin | Subjects from birth to 18 years old (exclusive)are to be treated with vancomycin for 10 days either as capsules (for subjects able to swallow) or oral solution (for the others) . |
| COMPLETED |
|
| NOT COMPLETED |
|
Only one subject was enrolled in Part A. Part B was not conducted due to early study termination. Consequently the baseline characteristics are from one subject only.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part A / Cohort A | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Due to the premature study termination, no subject was enrolled into Part B and consequently the percentage of subjects with a clinical cure could not be reported. | Posted | 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. | Due to the premature study termination, cadazolid concentrations were obtained from only one subject and pharmacokineitc plasma profile was not analyzed because of lack of meaningful data. | Posted | 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. | Due to the premature study termination, cadazolid concentrations were obtained from only one subject and pharmacokineitc plasma profile was not analyzed because of lack of meaningful data. | Posted | 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. | Due to the premature study termination, cadazolid concentrations were obtained from only one subject and pharmacokineitc plasma profile was not analyzed because of lack of meaningful data. | Posted | 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. | Due to premature termination, fecal sample was collected from only one subject, consequently mean values cannot be provided and no statistical analyses can be performed. | Posted | Number | mcg/g | 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). | Due to premature termination, data were collected from only one subject, consequently percentage of participants with clinical cure cannot be calculated and no statistical analyses can be performed | Posted | 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). | Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed. | Posted | 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. | Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed. | Posted | 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) | Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B | Posted | 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 | Due to premature termination, data were collected from only one subject, consequently KM estimates cannot be calculated and no statistical analyses can be performed | Posted | 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 | Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B | Posted | Count of Participants | Participants | 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 | Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B | Posted | Count of Participants | Participants | 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) | Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B | Posted | Count of Participants | Participants | 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. | Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B | Posted | Count of Participants | Participants | Day 17 (on average) |
|
|
From study treatment initiation up to Day 37 (i.e., 27 days after the end of treatment)
All adverse events (AE) which occurred at any time during the treatment period (10 days with cadazolid) and during the follow-up period (about 30 days) are reported. All AEs reported below occurred during the follow-up period.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Overall Study (Part A and Part B) | Only one subject was included in cohort A; no subject was enrolled in the other cohorts of Part A or Part B due to early study termination. | 0 | 1 | 0 | 1 | 1 | 1 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sore throat | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
Only one subject was enrolled due to early study termination. Consequently results are not meaningful and no statistical analyses could be performed.
Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| clinical trial disclosure desk | Actelion Pharmaceuticals Ltd | 0041615656565 | clinical-trials-disclosure@its.jnj.com |
| Prot_000.pdf |
| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| ID | Term |
|---|---|
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C000591679 | cadazolid |
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
|
| infants and toddlers (3 months to < 2 years |
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|
|
|
|