Clinical trial NCT02053181: Study to Investigate the Pharmacokinetics and Safety of Cadazolid in Patients With Clostridium Difficile Infection
Official title: A Phase 1, Open-label, Single Oral Dose Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Cadazolid in Patients With Severe Clostridium Difficile Infection (CDI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clostridium Difficile Infection
Keywords: Cadazolid
ACT-179811
Pharmacokinetics
Safety
Tolerability
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2014-02-03
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The study investigated the pharmacokinetics, safety, and tolerability of cadazolid in subjects with severe Clostridium difficile diarrhea (CDAD) and whether this influenced the quantity of cadazolid absorbed into the systemic circulation.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent prior to any study-mandated procedure.
* Non-pregnant females were to remain non-pregnant for 1 month after the end of the study. Female subjects of child-bearing potential must have had a negative serum pregnancy test at screening and must have used a reliable method of contraception
* Subjects with severe CDAD; Clostridium difficile infection (CDI) must have been microbiologically proven, using a validated enzyme-linked immunosorbent assay (ELISA) for the detection of C. difficile toxin A (TcdA) and/or C. difficile toxin B (TcdB). The severity of CDAD was assessed according to the current European Union guidelines - European Society of Clinical Microbiology and Infectious Diseases (ESCMID).
* Received oral vancomycin or oral/intravenous (i.v.) metronidazole therapy for the treatment of CDAD.
* Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria:

* Known hypersensitivity to any excipients of the drug formulation.
* Clinical evidence of any relevant disease other than CDAD and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drug.
* Veins unsuitable for i.v. puncture on either arm (e.g., veins that are difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).
* Subjects with rare hereditary fructose intolerance, glucose-galactose malabsorption, saccharase-isomaltase deficiency or previously undiagnosed diabetes mellitus.
* Subjects who have a life-threatening condition, which may be related to CDAD or other underlying illness.
* Any clinically relevant electrocardiogram (ECG) abnormality at screening.
* Subjects who were unable to swallow or have difficulty swallowing.
* Subjects with vomiting, ileus or not passing stool.
* Likelihood of death within 72 hours from any cause.
* Life-threatening or fulminant CDAD (White blood cell count \> 30 × 10\^9/L; temperature \> 40 °C; or septic shock, peritoneal signs or significant dehydration).
* History of ulcerative colitis or Crohn's disease.
* Loss of 250 mL or more of blood within 3 months prior to screening.
* Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
* Positive results from the human immunodeficiency virus (HIV) serology at screening.
* Legal incapacity or limited legal capacity at screening.
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of cadazolid
timeFrame: 144 hours
measure: Time to reach maximum plasma concentration (tmax) of cadazolid
timeFrame: 144 hours
measure: Area under the plasma concentration-time curve (AUC(0-144h)) of cadazolid
timeFrame: 144 hours
measure: Unchanged cadazolid in urine up to Day 7
timeFrame: 144 hours
measure: Unchanged cadazolid in faeces up to Day 7
timeFrame: 144 hours
Secondary outcomes:
measure: Change from baseline up to Day 7 in systolic blood pressure (SBP)
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in diastolic blood pressure (DBP)
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in pulse rate
timeFrame: 144 hours
measure: Change from baseline to Day 7 in body weight
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in heart rate
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in PQ interval (time interval from the beginning of the P wave to the beginning of the QRS complex)
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in QRS duration (time interval from the beginning of the Q wave to the end of the S wave)
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in QT (time interval from beginning of the Q wave until end of the T wave)
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in QT interval according to Bazett's correction (QTcB)
timeFrame: 144 hours
measure: Change from baseline up to Day 7 in QT interval according to Fridericia's correction (QTcF)
timeFrame: 144 hours
measure: Frequency of treatment-emergent ECG abnormalities from up to Day 7
timeFrame: 144 hours
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: Clinical Hospital for Infective Disease
Study officials:
affiliation: Actelion
name: Alison Mackie, MSc
role: STUDY_DIRECTOR
References:
citation: Gehin M, Desnica B, Dingemanse J. Minimal systemic and high faecal exposure to cadazolid in patients with severe Clostridium difficile infection. Int J Antimicrob Agents. 2015 Nov;46(5):576-81. doi: 10.1016/j.ijantimicag.2015.07.015. Epub 2015 Sep 3.