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

NCT02053181 | Completed Phase 1

• 1 other identifier: AC-061-103
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Clostridium Difficile Infection

Keywords

Cadazolid; ACT-179811; Pharmacokinetics; Safety; Tolerability

Outcome Measures

Primary Outcomes (5)

• Maximum plasma concentration (Cmax) of cadazolid

  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.

  144 hours

• Time to reach maximum plasma concentration (tmax) of cadazolid

  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.

  144 hours

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

  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.

  144 hours

• Unchanged cadazolid in urine up to Day 7

  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.

  144 hours

• Unchanged cadazolid in faeces up to Day 7

  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.

  144 hours

Secondary Outcomes (11)

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

  144 hours

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

  144 hours

• Change from baseline up to Day 7 in pulse rate

  144 hours

• Change from baseline to Day 7 in body weight

  144 hours

• Change from baseline up to Day 7 in heart rate

  144 hours

Study Arms (1)

Cadazolid

EXPERIMENTAL

Single oral dose of 3000 mg.

Drug: Cadazolid

Interventions

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.

Also known as: ACT-179811

Cadazolid

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Clinical Hospital for Infective Disease

Zagreb, 1000, Croatia

Location

Related Publications (1)

• 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.

  PMID: 26419191 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Interventions

cadazolid

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Alison Mackie, MSc

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2014
• First Posted: February 3, 2014
• Study Start: August 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: February 3, 2014

Record last verified: 2014-01

Locations

CR (1)