Skip to main content
OpenTrials
Completed

NCT Number: NCT02053181

Study to Investigate the Pharmacokinetics and Safety of Cadazolid in Patients With Clostridium Difficile Infection

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Clostridium Difficile Infection Bacterial Infections Bacterial Infections and Mycoses Clostridium Infections Gram-Positive Bacterial Infections Infections

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Hospital for Infective Disease

Zagreb, 1000, Croatia

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Cadazolid

Drug

Cadazolid was provided as dry powder for oral suspension (Amber glass bottles of 60 mL). The powder was reconstituted with tap water by a pharmacist immediately prior to dispensing to subjects.

Other names: ACT-179811

Primary outcomes

  1. Maximum plasma concentration (Cmax) of cadazolid

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing. Cmax was calculated on the basis of the blood sampling time points.

  2. Time to reach maximum plasma concentration (tmax) of cadazolid

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing. tmax was calculated on the basis of the blood sampling time points.

  3. Area under the plasma concentration-time curve (AUC(0-144h)) of cadazolid

    Time frame: 144 hours

    Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing. AUC(0-144) was calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification.

  4. Unchanged cadazolid in urine up to Day 7

    Time frame: 144 hours

    Urine was collected into standard-weight polyethylene containers over the following time intervals: 0-12 h, 12-24 h, 24-36 h, 36-48 h, 48-72 h, 72-96 h, 96-120 h, and 120-144 h. The concentration of cadazolid was determined using validated liquid chromatography-tandem mass spectrometry assays. The amount of drug excreted in the urine was obtained by multiplying the concentration of drug by the volume of matrix collected.

  5. Unchanged cadazolid in faeces up to Day 7

    Time frame: 144 hours

    Faeces were collected in pre-weighed polypropylene boxes. The concentration of cadazolid was determined using validated liquid chromatography-tandem mass spectrometry assays. The amount of drug excreted in the faeces was obtained by multiplying the concentration of drug by the volume of matrix collected.

Secondary outcomes

  1. Change from baseline up to Day 7 in systolic blood pressure (SBP)

    Time frame: 144 hours

    Blood pressure (systolic and diastolic) and pulse rate were measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm = writing arm). Measurements were recorded in the supine position after the subject had rested for a 5-minute period.

  2. Change from baseline up to Day 7 in diastolic blood pressure (DBP)

    Time frame: 144 hours

    Blood pressure (systolic and diastolic) and pulse rate were measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm = writing arm). Measurements were recorded in the supine position after the subject had rested for a 5-minute period.

  3. Change from baseline up to Day 7 in pulse rate

    Time frame: 144 hours

    Blood pressure (systolic and diastolic) and pulse rate were measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm = writing arm). Measurements were recorded in the supine position after the subject had rested for a 5-minute period.

  4. Change from baseline to Day 7 in body weight

    Time frame: 144 hours

    Body weight was measured using the same weighing scales.

  5. Change from baseline up to Day 7 in heart rate

    Time frame: 144 hours

    Heart rate was determined from standard 12-lead electrocardiographs (ECGs) recorded in the supine position, after a 5-minute period of resting.

  6. 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)

    Time frame: 144 hours

    PQ interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.

  7. 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)

    Time frame: 144 hours

    QRS duration was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.

  8. Change from baseline up to Day 7 in QT (time interval from beginning of the Q wave until end of the T wave)

    Time frame: 144 hours

    QT interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.

  9. Change from baseline up to Day 7 in QT interval according to Bazett's correction (QTcB)

    Time frame: 144 hours

    QTcB interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting. The QTcB interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5 where RR is 60/heart rate)

  10. Change from baseline up to Day 7 in QT interval according to Fridericia's correction (QTcF)

    Time frame: 144 hours

    QTcF interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting. The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcB = QT/RR^0.33 where RR is 60/heart rate)

  11. Frequency of treatment-emergent ECG abnormalities from up to Day 7

    Time frame: 144 hours

    Treatment-emergent abnormalities were determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting. An ECG abnormality was considered treatment-emergent if it was not present during the screening period and/or at time of pre-dose assessment.

Sponsors and collaborators

Lead sponsor

Actelion

Industry

Registry information

Official study 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)

Important dates

Study start
2012
Primary completion
2012
Study completion
2012
First posted
Feb 3, 2014
Registry last updated
Feb 3, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.