To Examine The Effects Of Lapatinib On Orally And Intravenously Administered Midazolam In Cancer Patients
- Registration Number
- NCT00258050
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
To characterize the effect of repeat oral dose of lapatinib treatment on the pharmacokinetics of a single oral and single intravenous dose of midazolam in adult cancer patients. Also to assess the safety and tolerability of chronic oral lapatinib therapy in cancer patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Subjects with cancer Midazolam 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 with cancer Lapatinib 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.
- Primary Outcome Measures
Name Time Method Area under the concentration versus time curve (AUC) of midazolam 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. AUC of midazolam in the presence and absence of lapatinib will be determined.
Maximum observed concentration (Cmax) of midazolam 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.
Clearance (CL) of midazolam 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. CL of midazolam in the presence and absence of lapatinib will be determined.
Absolute bioavailability (F) of midazolam 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.
Half-life (t½) of midazolam 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. t1/2 of midazolam in the presence and absence of lapatinib will be determined.
- Secondary Outcome Measures
Name Time Method Number of subjects with abnormal blood pressure Up to Month 7 Systolic and diastolic blood pressure will be measured.
Number of subjects with abnormal heart rate Up to Month 7 Heart rate will be measured.
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) Up to Month 7 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.
Time of maximum observed concentration (tmax) of midazolam 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.
Volume of distribution (Vss) of midazolam 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.
Number of subjects with abnormal clinical chemistry parameters Up to Month 7 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).
Number of subjects with abnormal hematology parameters Up to Month 7 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Chapel Hill, North Carolina, United States