Study to Investigate the Pharmacokinetics and Safety of Cadazolid in Patients With Clostridium Difficile Infection
31. januar 2014 oppdatert av: Actelion
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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
6
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Zagreb, Kroatia, 1000
- Clinical Hospital for Infective Disease
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 80 år (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Cadazolid
Single oral dose of 3000 mg.
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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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum plasma concentration (Cmax) of cadazolid
Tidsramme: 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.
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144 hours
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Time to reach maximum plasma concentration (tmax) of cadazolid
Tidsramme: 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.
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144 hours
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Area under the plasma concentration-time curve (AUC(0-144h)) of cadazolid
Tidsramme: 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.
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144 hours
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Unchanged cadazolid in urine up to Day 7
Tidsramme: 144 hours
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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.
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144 hours
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Unchanged cadazolid in faeces up to Day 7
Tidsramme: 144 hours
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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.
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144 hours
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Change from baseline up to Day 7 in systolic blood pressure (SBP)
Tidsramme: 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.
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144 hours
|
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Change from baseline up to Day 7 in diastolic blood pressure (DBP)
Tidsramme: 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.
|
144 hours
|
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Change from baseline up to Day 7 in pulse rate
Tidsramme: 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.
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144 hours
|
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Change from baseline to Day 7 in body weight
Tidsramme: 144 hours
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Body weight was measured using the same weighing scales.
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144 hours
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Change from baseline up to Day 7 in heart rate
Tidsramme: 144 hours
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Heart rate was determined from standard 12-lead electrocardiographs (ECGs) recorded in the supine position, after a 5-minute period of resting.
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144 hours
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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)
Tidsramme: 144 hours
|
PQ interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
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144 hours
|
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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)
Tidsramme: 144 hours
|
QRS duration was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
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144 hours
|
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Change from baseline up to Day 7 in QT (time interval from beginning of the Q wave until end of the T wave)
Tidsramme: 144 hours
|
QT interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
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144 hours
|
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Change from baseline up to Day 7 in QT interval according to Bazett's correction (QTcB)
Tidsramme: 144 hours
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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)
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144 hours
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Change from baseline up to Day 7 in QT interval according to Fridericia's correction (QTcF)
Tidsramme: 144 hours
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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)
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144 hours
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Frequency of treatment-emergent ECG abnormalities from up to Day 7
Tidsramme: 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.
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144 hours
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studieleder: Alison Mackie, MSc, Actelion
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. august 2012
Primær fullføring (Faktiske)
1. september 2012
Studiet fullført (Faktiske)
1. september 2012
Datoer for studieregistrering
Først innsendt
30. januar 2014
Først innsendt som oppfylte QC-kriteriene
31. januar 2014
Først lagt ut (Anslag)
3. februar 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
3. februar 2014
Siste oppdatering sendt inn som oppfylte QC-kriteriene
31. januar 2014
Sist bekreftet
1. januar 2014
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- AC-061-103
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