- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00258050
To Examine The Effects Of Lapatinib On Orally And Intravenously Administered Midazolam In Cancer Patients
A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
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New Hampshire
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Lebanon, New Hampshire, Forenede Stater, 03756
- GSK Investigational Site
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North Carolina
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Chapel Hill, North Carolina, Forenede Stater, 27599
- GSK Investigational Site
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion criteria:
- Histologically confirmed, solid tumor refractory to standard therapy.
- Tumor for which there is no standard therapy.
- Able to swallow and retain oral medication.
- ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
- Provided written informed consent.
- Adequate bone marrow function.
- Serum creatinine is less than or equal to 1.5 mg/dL.
- Calculated creatinine clearance is greater than or equal to 60 ml/min based on Cockcroft and Gault.
- Total bilirubin is greater than or equal to the upper limit of normal of institutional values.
- Aspartate and alanine transaminase is less than or equal to 3 times the upper limit of the institutional values.
- Have a left ventricular ejection fraction (LVEF) greater than or equal to 40% based on electrocardiogram (ECHO) or multiple gated acquisition scan (MUGA).
- Resting oxygen saturations of greater than 90%.
Exclusion criteria:
- Pregnant or lactating female.
- Have malabsorption syndrome, a disease affecting gastrointestinal function.
- Resection of the stomach or small bowel.
- Evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease.
- Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product.
- Use of anilinoquinazolines, such as gefitinib [Iressa™], erlotinib [Tarceva™].
- Immediate or delayed hypersensitivity reaction to midazolam or any component of the formulation, including benzyl alcohol (cross-sensitivity with other benzodiazepines may exist).
- Has narrow-angle glaucoma which is a contraindication to midazolam use.
- Has received treatment with any investigational drug in the previous 4 weeks.
- Received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the past 14 days, with the exception of mitomycin C within the past 6 weeks.
- Currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
- Is taking regular doses of opiates that in the opinion of the investigator would put the patient at risk of clinically significant respiratory compromise when midazolam is administered.
- Physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Has Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Clinically significant electrocardiogram (ECG) abnormality.
- Clinically assessed to have inadequate venous access for protocol-related blood draws.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Subjects with cancer
In Part 1 of the study, subjects will be randomized to one of four sequences. All subjects will receive oral or intravenous (IV) midazolam on Days 1, 3, 9 and 11 as per assigned randomization scheme. Starting on Day 4 through Day 11, subjects will receive a daily dose of 1500 milligrams (mg) of oral lapatinib. In Part 2, which will begin on Day 12, the subjects will be required to take 1500 mg of lapatinib daily until removed from the study for disease progression, adverse events, withdrawal of consent, or transfer to another lapatinib study. |
Subjects will receive midazolam by oral or IV route on Days 1, 3, 9 and 11.
Oral midazolam was supplied as 3 mg tablets; IV midazolam was supplied as 1 milligram per milliliter (mg/L) sterile solution.
Andre navne:
Subjects will receive 1500 mg lapatinib by oral route once daily from Day 4.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Area under the concentration versus time curve (AUC) of midazolam
Tidsramme: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Blood samples will be collected at indicated time points for the determination of midazolam concentration.
AUC of midazolam in the presence and absence of lapatinib will be determined.
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Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Maximum observed concentration (Cmax) of midazolam
Tidsramme: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
|
Blood samples will be collected at indicated time points for the determination of midazolam concentration.
Cmax of midazolam in the presence and absence of lapatinib will be determined.
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Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Clearance (CL) of midazolam
Tidsramme: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Blood samples will be collected at indicated time points for the determination of midazolam concentration.
CL of midazolam in the presence and absence of lapatinib will be determined.
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Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Half-life (t½) of midazolam
Tidsramme: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Blood samples will be collected at indicated time points for the determination of midazolam concentration.
t1/2 of midazolam in the presence and absence of lapatinib will be determined.
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Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Absolute bioavailability (F) of midazolam
Tidsramme: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
|
Blood samples will be collected at indicated time points for the determination of midazolam concentration.
Absolute bioavailability of midazolam in the presence and absence of lapatinib will be determined.
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Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Time of maximum observed concentration (tmax) of midazolam
Tidsramme: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
|
Blood samples will be collected at indicated time points for the determination of midazolam concentration.
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Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Volume of distribution (Vss) of midazolam
Tidsramme: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Blood samples will be collected at indicated time points for the determination of midazolam concentration.
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Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
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Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Tidsramme: Up to Month 7
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An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events may require medical or surgical intervention to prevent one of the other outcomes listed above.
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Up to Month 7
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Number of subjects with abnormal clinical chemistry parameters
Tidsramme: Up to Month 7
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The following clinical chemistry parameters were evaluated: sodium, potassium, total carbon dioxide (CO2), calcium, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and blood urea nitrogen (BUN).
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Up to Month 7
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Number of subjects with abnormal hematology parameters
Tidsramme: Up to Month 7
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The following hematology parameters were evaluated: hemoglobin, hematocrit, red blood cell count, white blood cell count, neutrophil count, lymphocyte count, monocyte count, eosinophil count and basophil count.
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Up to Month 7
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Number of subjects with abnormal blood pressure
Tidsramme: Up to Month 7
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Systolic and diastolic blood pressure will be measured.
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Up to Month 7
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Number of subjects with abnormal heart rate
Tidsramme: Up to Month 7
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Heart rate will be measured.
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Up to Month 7
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Samarbejdspartnere og efterforskere
Sponsor
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Hudsygdomme
- Neoplasmer
- Neoplasmer efter sted
- Brystsygdomme
- Brystneoplasmer
- Lægemidlers fysiologiske virkninger
- Neurotransmittermidler
- Molekylære mekanismer for farmakologisk virkning
- Depressive midler til centralnervesystemet
- Enzymhæmmere
- Bedøvelsesmidler, intravenøst
- Bedøvelsesmidler, general
- Bedøvelsesmidler
- Antineoplastiske midler
- Beroligende midler
- Psykotropiske stoffer
- Proteinkinasehæmmere
- Hypnotika og beroligende midler
- Adjuvanser, anæstesi
- Anti-angst midler
- GABA modulatorer
- GABA agenter
- Midazolam
- Lapatinib
Andre undersøgelses-id-numre
- EGF10015
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