Clostridium Difficile InfectionPhase 1NCT02053181
Study to Investigate the Pharmacokinetics and Safety of Cadazolid in Patients With Clostridium Difficile Infection
A Phase 1 study testing Cadazolid in people with Clostridium Difficile Infection, run by Actelion at 1 site in Croatia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Clostridium Difficile Infection
- What is being tested?
- Cadazolid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteCroatia
- Study dates
- Aug 2012to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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
- Being tested
- Cadazolid
- Keywords
- Cadazolid, ACT-179811, Pharmacokinetics, Safety, Tolerability
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CadazolidDrug
Also called ACT-179811
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.
| Study group | Role | What they receive |
|---|---|---|
| Cadazolid | Experimental | Single oral dose of 3000 mg. Receives: Drug: Cadazolid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 144 hours
Secondary outcomes (11)
Change from baseline up to Day 7 in systolic blood pressure (SBP)
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.
Measured: 144 hours
Change from baseline up to Day 7 in diastolic blood pressure (DBP)
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.
Measured: 144 hours
Change from baseline up to Day 7 in pulse rate
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.
Measured: 144 hours
Change from baseline to Day 7 in body weight
Body weight was measured using the same weighing scales.
Measured: 144 hours
Change from baseline up to Day 7 in heart rate
Heart rate was determined from standard 12-lead electrocardiographs (ECGs) recorded in the supine position, after a 5-minute period of resting.
Measured: 144 hours
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)
PQ interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
Measured: 144 hours
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)
QRS duration was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
Measured: 144 hours
Change from baseline up to Day 7 in QT (time interval from beginning of the Q wave until end of the T wave)
QT interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
Measured: 144 hours
Change from baseline up to Day 7 in QT interval according to Bazett's correction (QTcB)
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)
Measured: 144 hours
Change from baseline up to Day 7 in QT interval according to Fridericia's correction (QTcF)
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)
Measured: 144 hours
Frequency of treatment-emergent ECG abnormalities from up to Day 7
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.
Measured: 144 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study startAug 2012
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Actelion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alison Mackie, MSc, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02053181
- Sponsor's protocol ID
- AC-061-103
- Status last verified
- Jan 2014
- First submitted
- 30 Jan 2014
- Last updated
- 3 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26419191
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02053181
- Acronym / sponsor ID
- AC-061-103
- Conditions
- Clostridium Difficile Infection
- Keywords
- Cadazolid, ACT-179811, Pharmacokinetics, Safety, Tolerability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- ActelionIndustry (pharma, biotech, devices)
- Study start
- Aug 2012
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 3 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cadazolid | Experimental | Drug: CadazolidSingle oral dose of 3000 mg. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CadazolidAlso: ACT-179811Cadazolid 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. | Drug | Cadazolid |
Primary outcome
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.
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.
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.
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.
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.
11 secondary outcomes
Change from baseline up to Day 7 in systolic blood pressure (SBP)
Time frame: 144 hours
Change from baseline up to Day 7 in diastolic blood pressure (DBP)
Time frame: 144 hours
Change from baseline up to Day 7 in pulse rate
Time frame: 144 hours
Change from baseline to Day 7 in body weight
Time frame: 144 hours
Change from baseline up to Day 7 in heart rate
Time frame: 144 hours
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
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
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
Change from baseline up to Day 7 in QT interval according to Bazett's correction (QTcB)
Time frame: 144 hours
Change from baseline up to Day 7 in QT interval according to Fridericia's correction (QTcF)
Time frame: 144 hours
Frequency of treatment-emergent ECG abnormalities from up to Day 7
Time frame: 144 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2014.
- Derived from this study: PubMed 26419191Gehin 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.
Related trials for Clostridium Difficile Infection
Not yet recruitingObservational study
Epidemiology of Clostridioides Difficile Infection (CDI) in Long-term Care Facilities, Assessment of Professional Practices Related to CDI Risk Prevention, and Strategies for Improving Care.
Clostridioides Difficile Infection
Active, not recruitingPhase 2
Autologous Fecal Microbiota Transplantation (Auto-FMT) for Prophylaxis of Clostridium Difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic Hematopoietic Stem Cell
Active, not recruitingObservational study
C. Difficile Toxin Levels in Stool From Healthy Individuals Following Standard of Care Antibiotic Treatment for CDI.
Clostridioides Difficile Infection Recurrence
RecruitingPhase 3
VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections
RecruitingEarly Phase 1
Prevention of Recurrence of Clostridioides Difficile Colitis With Ursodeoxycholic Acid (UCDA) as a Supplement to Standard Therapy
Clostridioides Difficile Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison Mackie, MSc study director
Actelion
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cadazolid in people with Clostridium Difficile Infection, run by Actelion at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum plasma concentration (Cmax) of cadazolid (time frame: 144 hours). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02053181, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2014.