- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01727128
Pharmacokinetic Study of BKM120 in Subjects With Hepatic Impairment
A Phase I, Multicenter, Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of BKM120 in Subjects With Mild, Moderate and Severe Hepatic Impairmen
Aperçu de l'étude
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Berlin, Allemagne, 14050
- Novartis Investigative Site
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Sofia, Bulgarie, 1618
- Novartis Investigative Site
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Moscow, Fédération Russe, 117198
- Novartis Investigative Site
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Subjects should be in good health (except for additional/ specific inclusion criteria related to hepatic impaired subjects) as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests of no significance at screening
- Subjects must weigh at least 45 kg to participate in this study, and must have a body mass index (BMI) from (18.5-35.0 kg/m2)
Subjects must be able to communicate well with the investigator, to understand the requirements of the study and agree to use strict contraception for 16 weeks after the last BKM120 dose
---Additional inclusion criteria Group 1 - control healthy subjects
Subjects should be matched to the hepatic impaired subjects of group 2 in gender, age (± 10 years), weight (± 20%), and BMI (±5%)
---Additional inclusion criteria Group 2 - hepatic impaired subjects
- Subjects with physical signs consistent with stable hepatic impairment
- Child-Pugh Clinical Assessment Score consistent with degree of hepatic impairment (mild , moderate or severe)
- Subjects must be free of significant medical disorders unrelated to the subject's hepatic disorder as judged by the investigator.
- Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L
- Platelet count ≥ 50 x 109 /L
- serum creatinine ≤ 1.5 x ULN
Exclusion Criteria:
- Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for the hepatic impaired subjects who due to their liver disease may be affected by significant medical problems which require frequent hospitalizations. Invasive systemic fungal infections need to be fully resolved prior to study entry
- Use of tobacco products within 2 weeks prior to dosing or during the study.
- Consumption of alcohol within 2 days prior to dosing or during the study
- Subjects with known ongoing alcohol and or/drug abuse within 1 month prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and/or at baseline
- Subjects not willing to avoid certain study prohibited food, drink, over the counter medicines and supplements
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
- Medical history of cardiac disease and/or clinically significant ECG abnormalities.
- History of clinically significant hematologic, renal, endocrinologic, pulmonary cardiovascular, hepatic, or allergic disease medically documented
- Medical history of relevant psychiatric disorders
- Subjects with Diabetes Mellitus or subjects with glucose levels out of normal range as judge by the investigator
History of immunodeficiency diseases, including Human Immunodeficiency Virus (HIV), as confirmed by (HIV-1, HIV-2) test
- Additional exclusion criteria Group 1 (matched healthy control subjects) History or presence of liver disease or liver injury as indicated by an abnormal liver function profile A positive Hepatitis C test or a positive Hepatitis B surface antigen (HBsAg)
- Additional exclusion criteria Group 2- hepatic impaired subjects
- Subjects with clinically significant abnormal findings, not consistent with clinical disease, upon physical examination, ECG or laboratory evaluation
- Any evidence of progressive liver disease (within the last 4 weeks prior to the screening visit) as indicated by liver transaminases, alkaline phosphatase and GGT or a ≥ 50% worsening of serum bilirubin or prothrombin time
- Total bilirubin > 6mg/dl
- Subject has ascites requiring intervention
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Science basique
- Répartition: Non randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Mild Hepatic Impaired Group
Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - mildly hepatically impaired
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Expérimental: Moderate Hepatic Impaired group
Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - moderately hepatically impaired
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Expérimental: Severe Hepatic Impaired Group
Subjects can only be enroled into this group if they fit the Child -Pugh score criteria of severity category - Severely hepatically impaired
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Expérimental: Control Group
Matching healthy control subjects who do not have hepatic impairment and are matched to the hepatic impaired subjects by sex, age, gender and BMI
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Plasma concentration of pharmacokinctis (PK) parameter Tmax
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter TMax (time to maximum concentration)
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Plasma concentration of PK parameter Cmax
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CMax (maximum concentration)
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Plasma concentration of PK parameter AUC-t
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-t (Area under the curve at specified timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s).
Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Plasma concentration of PK parameter AUC-last
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-last (Area under the curve at last timepoint) The specific key measure(s) or observation(s) that will be used to determine the effect of the intervention(s).
Example: Change in left ventricular end systolic volume (LVESD) as measured by echocardiography Time to tumor progression Overall tumor response
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Plasma concentration of PK parameter AUC-inf
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter AUC-inf (Area under the curve to time infinity)
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Plasma concentration of PK parameter CL/F
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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infMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter CL/F (clearance)
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Plasma concentration of PK parameter Vz/F
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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FMeasurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter Vz/F (Volume distribution)
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Plasma concentration of PK parameter terminal T 1/2
Délai: predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Measurment of effect of liver impairment on PK of BKM120 by assessment of the PK parameter terminal T 1/2 (terminal half-life)
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predose,0.5,1,1.5,2,3,4,6,8,12,24,48,72,96,144,192,240,288,336 hours post dose
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Adverse events severity
Délai: From baseline day-1 to 30 days post dose
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Severtiy of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
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From baseline day-1 to 30 days post dose
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Change from baseline in laboratory parameters
Délai: From baseline day-1 to 30 days post dose
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Change from baseline in hematological and biochemical laboratory parameters
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From baseline day-1 to 30 days post dose
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Change from baseline in ECG parameters
Délai: From baseline day-1 to 30 days post dose
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Change from baseline in ECG parameters
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From baseline day-1 to 30 days post dose
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Change from baseline between PK parameters and total bilirubin, prothrombin time or INR and serum albumin
Délai: From baseline day-1 to 15 days post dose
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Relationship between PK parameters and baseline hepatic function parameters
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From baseline day-1 to 15 days post dose
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measurement of plasma binding
Délai: From baseline day-1 to 15 days post dose
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Determination of the free fraction of BKM120 in plasmaexpressed weher relevant in terms of unbound drug concentration
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From baseline day-1 to 15 days post dose
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Adverse events frequency
Délai: From baseline day-1 to 30 days post dose
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Frequency of adverse events severity based on the CTCAE criteria to assess safety and tolerability of a single dose of BKM120
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From baseline day-1 to 30 days post dose
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Collaborateurs et enquêteurs
Parrainer
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- CBKM120C2104
- 2011-002311-28 (Numéro EudraCT)
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Essais cliniques sur BKM120
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ARCAGY/ GINECO GROUPComplété
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Novartis PharmaceuticalsComplétéTumeurs activées par la voie PI3KÉtats-Unis
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Novartis PharmaceuticalsNovartisRetiréTraitement du cancer du col de l'utérus métastatique ou localement avancéBrésil
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Prince of Songkla UniversityRésiliéCancer de l'oesophageThaïlande
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Novartis PharmaceuticalsComplété
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M.D. Anderson Cancer CenterNovartisComplété
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Hospices Civils de LyonInconnue
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Sofia Perea, Director Clinical Trials Unit.NovartisComplété
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Won KimNovartisRésiliéCancer de la prostate à haut risqueÉtats-Unis
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Novartis PharmaceuticalsComplétéCancer de l'endomètre avancéBelgique, France, Italie, Canada, Espagne, Australie, Allemagne, États-Unis, Japon, Brésil, Singapour, Fédération Russe, Pologne