- ICH GCP
- Rejestr badań klinicznych w USA
- Badanie kliniczne NCT01713036
Oral Bioavailability and Mass Balance Trial With Pimasertib
6 lipca 2017 zaktualizowane przez: Merck KGaA, Darmstadt, Germany
A Phase I, Open-Label, Single Center Trial to Investigate the Mass Balance, Metabolite Profile and Oral Bioavailability of Pimasertib in Cancer Patients With Locally Advanced or Metastatic Solid Tumors
This is a Phase 1, open-label, single centered trial to evaluate the mass balance, bioavailability and metabolism of pimasertib in cancer subjects with locally advanced or metastatic solid tumors.
Przegląd badań
Status
Zakończony
Interwencja / Leczenie
Typ studiów
Interwencyjne
Zapisy (Rzeczywisty)
6
Faza
- Faza 1
Kontakty i lokalizacje
Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.
Lokalizacje studiów
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Budapest, Węgry
- Research Site
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Kryteria uczestnictwa
Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.
Kryteria kwalifikacji
Wiek uprawniający do nauki
18 lat do 65 lat (Dorosły, Starszy dorosły)
Akceptuje zdrowych ochotników
Nie
Płeć kwalifikująca się do nauki
Męski
Opis
Inclusion Criteria:
- Male subject with pathologically confirmed solid tumor preferentially including, but not limited to pancreatic, thyroid, colorectal, lung, and renal cancer, or melanoma which is locally advanced or metastatic, and either refractory to the respective standard therapy for the disease or for which no effective standard therapy is available
- Subject has measurable and evaluable disease as defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1)
- Age greater than or equal to 18 years and less than or equal to 65 years
- Body mass index greater than or equal to 19 and less than or equal to 30 kilogram per meter square (kg/m^2)
- Subject has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to 1
- Male subjects with female partners of childbearing potential must be willing to use an adequate method of contraception during and for 4 weeks after the last dose of the trial medication. During this time, female partners should use a contraceptive method with a failure rate of less than 1 percent
- Subject has read and understood the informed consent form and is willing and able to give written informed consent before any trial related procedures are performed
Exclusion Criteria:
- Bone marrow impairment as evidenced by hemoglobin less than 10.0 gram per deciliter (g/dL), neutrophil count less than 1.5 * 10^9 per liter (/L), and/or platelets less than 100 * 10^9/L
- Renal impairment as evidenced by serum creatinine greater than 1.5 * upper limit of normal (ULN) and calculated creatinine clearance less than 60 milliliter per minute (mL/min) (Cockcroft Gault formula)
- Liver function and liver cell integrity abnormality as defined by total bilirubin greater than 1.5 * ULN, or aspartate transaminase (AST)/alanine transaminase (ALT) greater than 2.5 * ULN, for subjects with liver metastases AST/ALT greater than 5 * ULN
- Primary brain tumors or clinical evidence of active brain metastasis. Subjects with a history of previously treated brain tumor are eligible provided that 1 month following treatment they were stable by computed tomography (CT) scan without evidence of cerebral edema, and have no requirements for anticonvulsants or high doses of corticosteroids
- History of gastrointestinal disease, malabsorption syndrome or difficulty in swallowing, which in the investigator's opinion might impair the absorption of pimasertib
- Any gastric, small or large bowel surgery that may impact the absorption of pimasertib
- Known human immunodeficiency virus (HIV) positivity, active hepatitis
- Chemotherapy, radiotherapy, immunotherapy, or molecular targeted cancer therapy within the past 4 weeks or within 5 half-lives of the given drug, whatever is longer, prior to start of trial medication or concomitantly within this trial. This restriction does not apply to steroids and bisphosphonates
- Major surgical procedure within the last 8 weeks prior to start of trial medication
- History of uveitis and scleritis. Retinal pathology beyond normal age-related processes
- History of glaucoma. Subjects are excluded if intraocular pressure is above 21 millimeter of mercury (mmHg)
- Evidence of a retinal vein occlusion (RVO) on fluorescein angiogram or a history of RVO. Subjects are also excluded if on examination an ophthalmologist finds that their optic disc is at risk for a central RVO
- Life expectancy of less than 12 weeks
- Clinically relevant non-malignant disease which in the investigator's opinion would exclude the subject from the trial, such as significant cardiovascular, pulmonary, endocrine, renal and neurological disease or psychiatric disorder
- Treatment with strong inhibitors and/or inducers of cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4). Consumption of CYP3A4 enzyme inducing or inhibiting herbal drugs, fruit juices and beverages (example, grapefruit, grapefruit juice, quinine [tonic water], star fruit, St John's Wort) within 2 weeks prior to start of trial medication until the end of Day 21
- Participation in a drug trial within 30 days prior to start of trial medication. Participation in a trial involving administration of [14C] labeled compound(s) within last 6 months prior to start of trial medication
- Known hypersensitivity to any of the excipients used
- Inability to understand the protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial
- Legal incapacity or limited legal capacity
Plan studiów
Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nie dotyczy
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: Pimasertib
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Part A: Subjects will receive unlabeled pimasertib capsules orally at a single dose of 60 milligram (mg) on Day 1.
One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kilobecquerel (kBq) [14C] pimasertib will be administered as a bolus injection.
On Days 3-21 (except Day 8), subjects will receive unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID).
In the morning of Day 8, subjects will receive 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 megabecquerel (MBq) (70 microcuries [mcgCi]) of [14C] pimasertib orally.
In the evening of Day 8, subjects will receive the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally.
Part B : Subjects will be administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.
Inne nazwy:
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
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Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of [14C]-Pimasertib Following Intravenous (IV) Administration on Day 1
Ramy czasowe: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
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Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
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Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time Point (AUC0-t) of Pimasertib Following Oral Administration on Day 1
Ramy czasowe: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
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Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
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Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of [14C]-Pimasertib Following IV Administration on Day 1
Ramy czasowe: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
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Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
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Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of Pimasertib Following Oral Administration on Day 1
Ramy czasowe: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
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Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
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Oral Bioavailability of Pimasertib After Single Oral Dose of Unlabeled Pimasertib and Intravenous (IV) Single Tracer Dose of [14C] Pimasertib
Ramy czasowe: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1
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Oral bioavailability (F) was calculated using the formula=AUC0-inf oral/dose oral) / (AUC0-inf iv/dose iv) * 100%, where AUC0-inf is the area under the concentration time curve (AUC) from time zero to infinity.
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Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1
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Mass Balance: Amount of Total Radioactivity Recovered Into the Urine and Feces From Time Zero to the Last Sampling Time Point (Ae0-t)
Ramy czasowe: Urine: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours post [14C]-labeled pimasertib dose on Day 8; Feces: 0-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours post [14C]-labeled pimasertib dose on Day 8
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Recovery of total [14C]-radioactivity was determined in excreta, i.e., urine and feces at each sampling period subsequent to oral administration of [14C]-pimasertib on Day 8. Cumulative recovery of total [14C]-radioactivity in terms of percentage of dose recovered in urine and feces and total percentage of dose recovered was reported for the outcome measure.
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Urine: 0-4, 4-8, 8-12, 12-24, 24-48, 48-72, and 72-96 hours post [14C]-labeled pimasertib dose on Day 8; Feces: 0-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours post [14C]-labeled pimasertib dose on Day 8
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Plasma Concentrations of [14C] Pimasertib
Ramy czasowe: Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8
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Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8
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Plasma Concentrations of Pimasertib Metabolites
Ramy czasowe: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Plasma concentration of the Pimasertib metabolite M445 and M554 were presented for the outcome measure.
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Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Number of Metabolites Identified Overall and as Major
Ramy czasowe: Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8
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Identification and profiling of the metabolites was done.
The total number of metabolites and the number of metabolites identified as major were reported.
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Pre-dose 1.0, 2.0, 4.0, 10 and 24 hours post [14C]-labeled Pimasertib dose on Day 8
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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
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Maximum Observed Plasma Concentration (Cmax) of Unlabeled Pimasertib
Ramy czasowe: Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
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Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1
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Maximum Observed Plasma Concentration (Cmax) of Intravenous [14C] Pimasertib
Ramy czasowe: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
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Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] intravenous pimasertib dose on Day 1
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Time to Reach Maximum Plasma Concentration (Tmax) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib
Ramy czasowe: Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
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Pre-dose 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
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Apparent Terminal Elimination Rate Constant (λz) of Unlabeled Pimasertib and Intravenous [14C] Pimasertib
Ramy czasowe: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
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Apparent terminal elimination rate constant (λz) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
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Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
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Total Body Clearance of Unlabeled Pimasertib (CL/f) and Intravenous [14C] Pimasertib (CL)
Ramy czasowe: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
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The total body clearance of drug from plasma following oral administration (Cl/f) and the total body clearance of drug from plasma following intravenous administration was calculated by dividing the Dose with area under the plasma concentration time curve from time zero to infinity (AUC0 inf)=Dose/AUC0- inf.
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Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] labeled pimasertib dose on Day 1
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The Volume of Distribution of the Central or Plasma Compartment (Vc) of Intravenous [14C] Pimasertib
Ramy czasowe: Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] pimasertib dose on Day 1
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The volume of distribution of the central or plasma compartment (Vc) was calculated using the formula=Dose/C0
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Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post intravenous [14C] pimasertib dose on Day 1
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Apparent Volume of Distribution During the Terminal Phase Following Oral Administration (Vz/f) and the Apparent Volume of Distribution During the Terminal Phase Following Intravenous Administration (Vz) of [14C] Pimasertib
Ramy czasowe: Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1
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The apparent volume of distribution during the terminal phase following oral administration (Vz/f) and the apparent volume of distribution during the terminal phase following intravenous administration was calculated by using the formula=Dose/( AUC0-inf* λz).
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Pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 8, 10, 12, 16, 24, and 48 hours post unlabeled pimasertib dose on Day 1; Pre-dose, 0.5, 1, 1.5, 3, 5, 7, 9, 11, 15, 23, and 47 hours post [14C] labeled pimasertib dose on Day 1
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Maximum Observed Plasma Concentration (Cmax) of Total [14C] Radioactivity
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Unit of assessment was nanogram equivalent per milliliter (ng eq/mL).
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Time to Reach Maximum Plasma Concentration (Tmax) of Total [14C] Radioactivity
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Area Under the Plasma Concentration Time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total [14C] Radioactivity
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Area under the plasma concentration time curve from time zero to the last sampling time at which the concentration is at or above the lower limit of quantification was calculated by using mixed log linear trapezoidal rule.
Unit of assessment was hour*nanogram equivalent per milliliter (hr*ng eq/mL).
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Total [14C] Radioactivity
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Area under the concentration time curve (AUC) from time zero to infinity (AUC0-inf) was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/λz.
Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Apparent Terminal Elimination Rate Constant (λz) of Total [14C] Radioactivity
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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λz of total [14C] radioactivity was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Apparent Terminal Half-life (t1/2) of Total [14C] Radioactivity
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Total Body Clearance of Total [14C] Radioactivity From Plasma Following Oral Administration (CL/f)
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
CL/f was influenced by the fraction absorbed.
Apparent body clearance of total radioactivity from plasma was calculated by dividing the dose with area under the plasma concentration time curve from zero to infinity (Dose/AUC0inf).
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Apparent Volume of Distribution of Total [14C] Radioactivity During the Terminal Phase Following Oral Administration (Vz/f)
Ramy czasowe: Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.
Vz/f of total radioactivity during the terminal phase was calculated by dividing the dose with the product of area under the plasma concentration time curve and apparent terminal rate constant (dose/AUC0inf*λz).
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Pre dose, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0, 48.0, 72.0, 96.0 and 168.0 hours post [14C]-labeled pimasertib dose on Day 8
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Maximum Observed Plasma Concentration (Cmax) of M445 and M554
Ramy czasowe: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Maximum observed plasma concentration (Cmax) for the metabolites M445 and M554 was calculated.
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Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Time to Reach Maximum Plasma Concentration (Tmax) of M445 and M554
Ramy czasowe: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Time to reach maximum plasma concentration (Tmax) for the metabolites M445 and M554 was calculated.
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Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) of M445 and M554
Ramy czasowe: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration is at or above the lower limit of quantification.
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Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of M445 and M554
Ramy czasowe: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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AUC from time 0 to infinity (AUC0-inf), was calculated from AUC0-t + AUCextra, where AUCextra = Clast calc/lambda z (λz).
Clast calc was the calculated plasma concentration at the last sampling time point at which plasma concentration was at or above the lower limit of quantification was measured and λz represents apparent terminal elimination rate constant.
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Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Apparent Terminal Elimination Rate Constant (λz) of M445 and M554
Ramy czasowe: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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The λz of M445 and M554 was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
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Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Apparent Terminal Half-life (t1/2) of M445 and M554
Ramy czasowe: Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Predose, 1.0, 2.0, 4.0, 10 and 24 hour post [14C]-labeled pimasertib dose on Day 8
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Fraction Unbound of [14C] Pimasertib
Ramy czasowe: 1.5 hour post [14C]-labeled pimasertib dose on Day 8
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Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration multiplied by 100.
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1.5 hour post [14C]-labeled pimasertib dose on Day 8
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Blood/ Plasma Concentration Ratios of Total [14C] Radioactivity
Ramy czasowe: 1.5 hour post [14C]-labeled pimasertib dose on Day 8
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1.5 hour post [14C]-labeled pimasertib dose on Day 8
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Part B: Number of Subjects Who Experienced Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)
Ramy czasowe: From the screening every 2 cycles until end of the treatment, assessed up to 18 months
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Anti tumor activity defined as CR, PR, or stable disease and PD based on the investigator tumor evaluations performed every 2 cycles in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
CR =Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (<)10 millimeter (mm); PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions; SD= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference.
For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size <10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones.
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From the screening every 2 cycles until end of the treatment, assessed up to 18 months
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Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation
Ramy czasowe: Part A and B: From the first dose of study drug administration until 30+/-2 days after the last dose of study drug administration, assessed up to 18 months
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Treatment-emergent are events between first dose of study drug administration until 30+/-2 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.
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Part A and B: From the first dose of study drug administration until 30+/-2 days after the last dose of study drug administration, assessed up to 18 months
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Współpracownicy i badacze
Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.
Sponsor
Śledczy
- Dyrektor Studium: Medical Responsible, Merck Serono SA, an affiliate of Merck KGaA, Darmstadt, Germany
Publikacje i pomocne linki
Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.
Publikacje ogólne
- Scheible H, Kraetzer F, Marx A, Johne A, Wimmer E. Metabolism of the MEK1/2 Inhibitor Pimasertib Involves a Novel Conjugation with Phosphoethanolamine in Patients with Solid Tumors. Drug Metab Dispos. 2017 Feb;45(2):174-182. doi: 10.1124/dmd.116.072934. Epub 2016 Dec 1.
- von Richter O, Massimini G, Scheible H, Udvaros I, Johne A. Pimasertib, a selective oral MEK1/2 inhibitor: absolute bioavailability, mass balance, elimination route, and metabolite profile in cancer patients. Br J Clin Pharmacol. 2016 Dec;82(6):1498-1508. doi: 10.1111/bcp.13078. Epub 2016 Sep 19.
Daty zapisu na studia
Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
30 listopada 2012
Zakończenie podstawowe (Rzeczywisty)
31 lipca 2014
Ukończenie studiów (Rzeczywisty)
31 lipca 2014
Daty rejestracji na studia
Pierwszy przesłany
13 września 2012
Pierwszy przesłany, który spełnia kryteria kontroli jakości
23 października 2012
Pierwszy wysłany (Oszacować)
24 października 2012
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
15 sierpnia 2017
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
6 lipca 2017
Ostatnia weryfikacja
1 lipca 2017
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Inne numery identyfikacyjne badania
- EMR 200066-008
- 2012-002562-12 (Numer EudraCT)
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .
Badania kliniczne na Pimasertib
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EMD SeronoSanofiZakończonyRak jajnikaStany Zjednoczone, Belgia, Kanada, Australia, Hiszpania, Francja, Polska
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Diakonhjemmet HospitalOslo University Hospital; University Hospital of North Norway; Helse Nord-Trøndelag... i inni współpracownicyRekrutacyjnyZdarzenie niepożądane pochodzenia immunologicznegoNorwegia
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EMD SeronoSanofiZakończonyCzerniak | Rak piersi | Rak jelita grubego | Niedrobnokomórkowego raka płuca | Guz lity z przerzutami | Miejscowo zaawansowany guz lityStany Zjednoczone, Włochy, Hiszpania
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EMD SeronoMerck KGaA, Darmstadt, GermanyZakończonyN-Ras lokalnie zaawansowany lub przerzutowy złośliwy czerniak skóryStany Zjednoczone, Szwecja, Australia, Francja, Włochy, Afryka Południowa, Hiszpania, Zjednoczone Królestwo, Niemcy, Holandia, Izrael, Nowa Zelandia, Belgia, Szwajcaria
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Merck KGaA, Darmstadt, GermanyMerck Serono Co., Ltd., JapanZakończonyRak wątrobowokomórkowy | Zaawansowane guzy liteJaponia
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Merck KGaA, Darmstadt, GermanyMerck Serono S.A., GenevaZakończonyNowotwór | Guzy liteFrancja, Belgia, Australia, Holandia
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Day One Biopharmaceuticals, Inc.RekrutacyjnyCzerniak | Rak jelita grubego | Guz lity | Niedrobnokomórkowego raka płuca | Rak pęcherza | Rak tarczycy, brodawkowaty | Gwiaździak pilocytarny | Rak urotelialny pęcherza moczowego | Niedrobnokomórkowy gruczolakorak | Mutacja MEK | Mutacja RAS | Rak groniasty trzustki | Mutacja RAF | Amplifikacja genu CRAF | Amplifikacja genu... i inne warunkiStany Zjednoczone, Kanada, Republika Korei, Hiszpania, Australia, Belgia, Francja
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BeiGeneAktywny, nie rekrutującyNawracający lub przerzutowy rak nosogardzieliChiny, Tajwan, Tajlandia
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EMD SeronoZakończonyBiałaczka, szpikowa, ostra | Nowotwory hematologiczneStany Zjednoczone, Francja
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Australian & New Zealand Children's Haematology...The Hospital for Sick Children; Kazia Therapeutics Limited; Day One Biopharmaceuticals... i inni współpracownicyJeszcze nie rekrutacjaRak dzieciństwa | Oporny na leczenie rak | Nawracający rak | Guz lity z dzieciństwa | Nowotwór mózgu u dzieciAustralia, Kanada