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

• Sponsor: Actelion (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03105479
• Collaborator: (none)
• Enrollment: 1
• Locations: 20
• Arms: 7
• Actual Duration (Months): 12.1
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Clostridium Difficile Infection	Drug: Cadazolid; Drug: Vancomycin capsule; Drug: Vancomycin solution	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Assessor masking in Part B only (no masking in Part A)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 14, 2017
• Actual Primary Completion Date: Apr 17, 2018
• Actual Study Completion Date: Apr 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Cadazolid; Granules for oral suspension to be administered twice daily; Other Names: ACT-179811
Experimental: Part A / Cohort B 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).	Drug: Cadazolid; Granules for oral suspension to be administered twice daily; Other Names: ACT-179811
Experimental: Part A / Cohort C 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.	Drug: Cadazolid; Granules for oral suspension to be administered twice daily; Other Names: ACT-179811
Experimental: Part A/ Cohort D 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.	Drug: Cadazolid; Granules for oral suspension to be administered twice daily; Other Names: ACT-179811
Experimental: Part A/ Cohort E 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.	Drug: Cadazolid; Granules for oral suspension to be administered twice daily; Other Names: ACT-179811
Experimental: Part B / 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.	Drug: Cadazolid; Granules for oral suspension to be administered twice daily; Other Names: ACT-179811
Active Comparator: Part B / Vancomycin 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 .	Drug: Vancomycin capsule; Capsule containing 125 mg of vancomycin to be administered orally 4 times a day; Drug: Vancomycin solution; Vancomycin powder to be administered as oral solution at a dose of 40 mg/kg/day, 3 to 4 times a day

Outcome Measures

Primary Outcome Measures

1. 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

2. 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.

3. 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.

4. 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.

5. 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.

Secondary Outcome Measures

1. 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).

2. 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).

3. 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.

4. 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)

5. 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

6. 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

7. 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

8. 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)

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Snake River Research, PLLC	Idaho Falls	Idaho	United States	83404
2	University of Chicago, Dept. Of Medicine	Chicago	Illinois	United States	60637
3	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana	United States	71103
4	SUNY Upstate Medical University - Upstate Golisano Children's Hospital (GCH) - Pediatric Designated AIDS Center	Syracuse	Ohio	United States	13210
5	Texas Children's Hospital Feigin Cente	Houston	Texas	United States	77030
6	Universitair Ziekenhuis Brussel - Kinderziekenhuis	Jette		Belgium	1090
7	Infection Prevention & Control, AGW5 Foothills Medical Center 1403 29th Street N.W.	Calgary		Canada	T2N 2T9
8	FN Brno	Brno		Czechia	62500
9	Egyesített Szent István és Szent László Kórház - Rendelőintézet / Gyermekinfektológiai Osztály	Budapest		Hungary	1097
10	Pándy Kálmán Megyei Kórház	Gyula		Hungary	5700
11	Ospedale Buzzi	Milano		Italy	20154
12	Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Pediatrico Bambino Gesu	Roma		Italy	00165
13	Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza	Bydgoszcz		Poland	85-030
14	Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem	Poznan		Poland	61-734
15	Gabinet Lekarski Bartosz Korczowski	Rzeszow		Poland	35-302
16	Klinika Gastroenterologii, Hepatologii, Zaburzeń Odżywiania i Pediatrii, Instytut "Pomnik - Centrum Zdrowia Dziecka"	Warsaw		Poland	04-730
17	Institutul National De Boli Infectioase "Prof. Dr. Matei Bals", sectia IX pediatrie	Bucharest		Romania	21105
18	Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi, Clinica de Boli Infectioase I,	Iasi		Romania	700116
19	Hospital Sant Joan de Déu, Esplugues	Barcelona		Spain	8950
20	Hospital Universitario Infantil LA PAZ	Madrid		Spain	28046

Sponsors and Collaborators

• Actelion

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 1, 2017

More Information

Publications

None provided.

• Responsible Party: Actelion
• ClinicalTrials.gov Identifier: NCT03105479
• Other Study ID Numbers: AC-061A303; 2015-004805-17
• First Posted: Apr 10, 2017
• Last Update Posted: Apr 3, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Actelion: vancomycin; children; cadazolid; clostridium difficile associated diarrhea
• Additional relevant MeSH terms: Clostridium Infections; Diarrhea; Vancomycin

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Part A / Cohort A	Part A / Cohort B	Part A / Cohort C	Part A/ Cohort D	Part A/ Cohort E	Part B / Cadazolid	Part B / Vancomycin
Arm/Group Description	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.	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)).	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).	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).	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). .	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.	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) .
Period Title: Overall Study
STARTED	1	0	0	0	0	0	0
COMPLETED	1	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A / Cohort A
Arm/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.
Overall Participants	1
Age, Customized (Count of Participants)
Adolescents (12 years to < 18 years)	1 100%
Children (2 years to < 12 years	0 0%
infants and toddlers (3 months to < 2 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Clinical Cure Rate During Part B
Description	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
Time Frame	Day 10 (End of Treatment) + 2 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part B
Arm/Group Description	Due to early termination of the study, no subject was enrolled into Part B.
Measure Participants	0

2. Primary Outcome

Title	Maximal Plasma Concentration (Cmax) of Cadazolid During Part A
Description	Blood samples are collected at different timepoints on Day 10 for the determination of cadazolid Cmax after 10 days of treatment.
Time Frame	Day 10 (End of Treatment)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A / Cohort A
Arm/Group Description	One Subject aged between 12 and 18 years old received cadazolid 500 mg per day for 10 days.
Measure Participants	0

3. Primary Outcome

Title	Time to Reach Cmax (Tmax) of Cadazolid During Part A
Description	Blood samples are collected at different timepoints to determine the time when the maximal plasma concentration of cadazolid is reached.
Time Frame	Day 10 (End of Treatment)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A / Cohort A
Arm/Group Description	One Subject aged between 12 and 18 years old received cadazolid 500 mg per day for 10 days.
Measure Participants	0

4. Primary Outcome

Title	Area Under the Plasma Concentration Time Curve (AUC) of Cadazolid During Part A
Description	Blood samples are collected at different timepoints for the determination of the cadazolid AUC over one dosing interval (0-12h) on Day 10.
Time Frame	Day 10 (End of Treatment)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A / Cohort A
Arm/Group Description	One Subject aged between 12 and 18 years old received cadazolid 500 mg per day for 10 days.
Measure Participants	0

5. Primary Outcome

Title	Fecal Concentrations of Cadazolid During Part A
Description	A fecal sample is collected as the end-of-treatment visit in all participants in Part A.
Time Frame	Day 10 (End of Treatment)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Part A / Cohort A
Arm/Group Description	One Subject aged between 12 and 18 years old received cadazolid 500 mg per day for 10 days.
Measure Participants	1
Number [mcg/g]	4520

6. Secondary Outcome

Title	Clinical Cure Rate During Part A
Description	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 Frame	Day 10 (End of Treatment) + 2 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part A / Cohort A
Arm/Group Description	One Subject aged between 12 and 18 years old received cadazolid 500 mg per day for 10 days.
Measure Participants	0

7. Secondary Outcome

Title	Sustained Clinical Cure Rate During Part A and Part B
Description	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).
Time Frame	Day 40 (on average)

Outcome Measure Data

Analysis Population Description

Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed.

Arm/Group Title	Part A / Cohorts A to E	Part B / Cadazolid
Arm/Group Description	Only one subject was included in cohort A; no subject was enrolled in the other cohorts due to early study termination.	No subject was enrolled in cohort B due to early study termination.
Measure Participants	0	0

8. Secondary Outcome

Title	Recurrence Rate During Part A and Part B
Description	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 Frame	Day 40 (on average)

Outcome Measure Data

Analysis Population Description

Due to the premature termination of the study and consequent lack of meaningful data, no analyses were performed.

Arm/Group Title	Part A / Cohorts A to E	Part B / Cadazolid
Arm/Group Description	Only one subject was included in cohort A; no subject was enrolled in the other cohorts due to early study termination.	No subject was enrolled in cohort B due to early study termination.
Measure Participants	0	0

9. Secondary Outcome

Title	Time to Recurrence in Part B
Description	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)
Time Frame	Day 40 (on average)

Outcome Measure Data

Analysis Population Description

Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B

Arm/Group Title	Part B
Arm/Group Description	Due to early termination of the study, no subject was enrolled into Part B.
Measure Participants	0

10. Secondary Outcome

Title	Time to Resolution of Diarrhea in Part B
Description	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
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

Due to premature termination, data were collected from only one subject, consequently KM estimates cannot be calculated and no statistical analyses can be performed

Arm/Group Title	Part B
Arm/Group Description	Due to early termination of the study, no subject was enrolled into Part B.
Measure Participants	0

11. Secondary Outcome

Title	Adverse Events Leading to Premature Discontinuation of Study Treatment
Description	Number of participants who prematurely discontinued the study treatment due to an adverse event
Time Frame	Up to Day 10

Outcome Measure Data

Analysis Population Description

Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B

Arm/Group Title	Part A / Cohorts A to E	Part B / Cadazolid
Arm/Group Description	Only one subject was included in cohort A; no subject was enrolled in the other cohorts due to early study termination.	No subject was enrolled in cohort B due to early study termination.
Measure Participants	1	0
Count of Participants [Participants]	0 0%

12. Secondary Outcome

Title	Marked Abnormalities in Clinical Laboratory Parameters
Description	Number of participants with any marked abnormalities in laboratory parameters up to 7 days after end of treatment
Time Frame	Day 17 (on average)

Outcome Measure Data

Analysis Population Description

Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B

Arm/Group Title	Part A / Cohorts A to E	Part B / Cadazolid
Arm/Group Description	Only one subject was included in cohort A; no subject was enrolled in the other cohorts due to early study termination.	No subject was enrolled in cohort B due to early study termination.
Measure Participants	1	0
Count of Participants [Participants]	0 0%

13. Secondary Outcome

Title	Marked Abnormalities in Vital Signs
Description	Number of subjects with any treatment-emergent abnormalities in vital signs (up to 7 days after end of treatment)
Time Frame	Day 17 (on average)

Outcome Measure Data

Analysis Population Description

Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B

Arm/Group Title	Part A / Cohorts A to E	Part B / Cadazolid
Arm/Group Description	Only one subject was included in cohort A; no subject was enrolled in the other cohorts due to early study termination.	No subject was enrolled in cohort B due to early study termination.
Measure Participants	1	0
Count of Participants [Participants]	0 0%

14. Secondary Outcome

Title	Treatment-emergent Adverse Events (TEAES)
Description	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.
Time Frame	Day 17 (on average)

Outcome Measure Data

Analysis Population Description

Due to premature termination, no subject was enrolled in Part B. Consequently, no data can be reported during Part B

Arm/Group Title	Part A / Cohorts A to E	Part B / Cadazolid
Arm/Group Description	Only one subject was included in cohort A; no subject was enrolled in the other cohorts due to early study termination.	No subject was enrolled in cohort B due to early study termination.
Measure Participants	1	0
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	From study treatment initiation up to Day 37 (i.e., 27 days after the end of treatment)
Adverse Event Reporting Description	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.
Arm/Group Title	Overall Study (Part A and Part B)
Arm/Group Description	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.
All Cause Mortality
	Overall Study (Part A and Part B)
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Overall Study (Part A and Part B)
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Overall Study (Part A and Part B)
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Gastrointestinal disorders
Vomiting	1/1 (100%)	1
Nervous system disorders
Headache	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Sore throat	1/1 (100%)	1

Limitations/Caveats

Only one subject was enrolled due to early study termination. Consequently results are not meaningful and no statistical analyses could be performed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.