- ICH GCP
- Registre américain des essais cliniques
- Essai clinique 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
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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New Hampshire
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Lebanon, New Hampshire, États-Unis, 03756
- GSK Investigational Site
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North Carolina
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Chapel Hill, North Carolina, États-Unis, 27599
- GSK Investigational 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:
- 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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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.
Autres noms:
Subjects will receive 1500 mg lapatinib by oral route once daily from Day 4.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Area under the concentration versus time curve (AUC) of midazolam
Délai: 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
Délai: 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.
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
Délai: 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
Délai: 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
Délai: 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.
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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Time of maximum observed concentration (tmax) of midazolam
Délai: 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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Volume of distribution (Vss) of midazolam
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
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
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies de la peau
- Tumeurs
- Tumeurs par site
- Maladies du sein
- Tumeurs mammaires
- Effets physiologiques des médicaments
- Agents neurotransmetteurs
- Mécanismes moléculaires de l'action pharmacologique
- Dépresseurs du système nerveux central
- Inhibiteurs d'enzymes
- Anesthésiques intraveineux
- Anesthésiques, général
- Anesthésiques
- Agents antinéoplasiques
- Agents tranquillisants
- Médicaments psychotropes
- Inhibiteurs de protéine kinase
- Hypnotiques et sédatifs
- Adjuvants, Anesthésie
- Agents anti-anxiété
- Modulateurs GABA
- Agents GABA
- Midazolam
- Lapatinib
Autres numéros d'identification d'étude
- EGF10015
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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