- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica 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
Panoramica dello studio
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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Sofia, Bulgaria, 1618
- Novartis Investigative Site
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Moscow, Federazione Russa, 117198
- Novartis Investigative Site
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Berlin, Germania, 14050
- Novartis Investigative Site
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Scienza basilare
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione incrociata
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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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Sperimentale: 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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Sperimentale: 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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Sperimentale: 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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Plasma concentration of pharmacokinctis (PK) parameter Tmax
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Adverse events severity
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- CBKM120C2104
- 2011-002311-28 (Numero EudraCT)
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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