Cancer
Conditions
Keywords
cancer, cardiac repolarization, Holter monitor, pharmacokinetics, GW572016, lapatinib, QTc interval, safety, ECG
Brief summary
This study will estimate the effect of lapatinib on cardiac repolarization (QTc interval duration) in subjects with advanced solid tumors. The study treatment period will occur over five days and an End of Study visit will be conducted on Day 8 (or no later than 3 days beyond Day 8). Subjects will receive placebo that mimics lapatinib for 2 days as three separate doses given 12 hours apart (8 tablets/dose) and lapatinib (2000mg) for 2 days as three separate doses given 12 hours apart (8 tablets/dose). Subjects will not know when they are receiving placebo vs. lapatinib. Digital 12-lead ECG recordings will be extracted from continuous ECG recordings obtained via a Holter monitor to measure QTc interval duration. Triplicate ECG measurements of QTc interval will be taken at pre-specified times at Day 1 (Baseline) and pre-dose and up to 24 hours after the third dose of placebo or lapatinib on Study Days 2 and 4. Pharmacokinetic sampling will occur immediately following each pre-specified QTc measurement in subjects dosed with placebo or lapatinib. Subjects who complete participation in this study, if they are eligible, will be offered the option to continue treatment with lapatinib, either alone or in combination with other oncology drugs in pre-selected anticancer regimens, in a continuation protocol, EGF111767.
Interventions
DRUGlapatinib
lapatinib commercial tablet, 2000mg, will be given as three separate doses (8 tablets/dose) given 12 hours apart over a 2 day period
DRUGplacebo matching lapatinib
placebo matching lapatinib will be given as three separate doses (8 tablets/dose) given 12 hours apart over a 2 day period
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of: Metastatic breast cancer that over-expresses ErbB2 OR Recurrent, advanced, or metastatic solid tumor malignancy (including breast cancer that does not over-express ErbB2) that is refractory to standard therapies, for which there is no approved therapy, or for which lapatinib in combination with one of the permitted anti-cancer regimens specified in the continuation study EGF111767 may provide clinical benefit. * A female subject must be of non-childbearing potential or willing to use acceptable contraception. * A male subject with a female partner of childbearing potential must agree to use acceptable contraception. * Is able to swallow and retain oral medication and does not have uncontrolled emesis. * ECOG performance status 0 to 1. * Adequate bone marrow function: ANC (absolute neutrophil count) \>/=1.5 x 10\^9/L, Hemoglobin \>/=9 g/dL, Platelets \>/=75 x 10\^9/L. * Albumin \>/=3 g/dL. * Serum bilirubin \</=1.5 x ULN. * AST and ALT \</=3 x ULN . * Serum Creatinine \</=1.5 mg/dL or Calculated Creatinine Clearance \>/= 50 mL/min. * Serum potassium and magnesium levels within normal limits. * Has a LVEF within the normal institutional range (or \>/=50%).
Exclusion criteria
* Any of the following ECG findings: QTcF interval \>480 msec, PR interval \>240 msec or \</=110 msec, Bradycardia defined as sinus rate \<50 beats per minute. * Cardiac conduction abnormalities denoted by any of the following: Evidence of second-degree (type II) or third-degree atrioventricular block, Evidence of ventricular pre-excitation, Electrocardiographic evidence of complete left bundle branch block (LBBB), Intraventricular conduction delay with QRS duration \>120 msec, Atrial fibrillation, Presence of cardiac pacemaker. * History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease or other clinically significant cardiac disease. * Personal history of long-QT syndrome. * Is pregnant or lactating. * Has malabsorption syndrome, or has undergone a resection or bypass of the distal stomach and pylorus, or small bowel. * Has acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment). * Has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease. Subjects with brain metastases treated by surgery and/or radiotherapy are eligible if neurologically stable and do not require steroids or anticonvulsants for at least 28 days prior to the first dose of study drug. * Has known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to the investigational product. * Has received anti-cancer therapy (including chemotherapy, radiation therapy, immunotherapy, biologic therapy, investigational therapy, surgery, or hormonal therapy) within 14 days prior to the first dose of study medication. * Is receiving any prohibited medication or consuming any food or beverage within the timeframe indicated on the prohibited medication list in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | Baseline (BL) (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours (hr) post-dose on Day 2 for placebo (PBO). Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib (LAP). | A Holter monitor is an ambulatory portable device used for continuously monitoring the cardiovascular system. Three replicate electrocardiograms (ECGs) were collected at 30, 15, and 0 minutes prior to the administration of study treatment (trt) on Days 1 and 3 and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 2 and 4. The 3 readings at each time point (TP) were averaged prior to any analysis. BL is the average of the pre-dose QTcF values (triplicate) taken on Day 1 for PBO and on Day 3 for LAP. Mean change from BL was calculated by subtracting the BL values from individual QTcF for each TP. BL adjusted mean difference in absolute QTcF between LAB and PBO (trt difference) with the corresponding 90% confidence interval (CI) was estimated for each TP (pre-dose and 1, 2, 3, 4, 6, 8, 10, 12, and 24-hr post-dose). Trt difference analysis was performed by a repeated measures analysis of variance adjusted for trt group, TP, and trt group\*TP interaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib. | The number of participants with 12-lead Holter ECG findings of normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) are reported. Abnormal ECG findings or change in ECG morphological patterns were based on the ECG interpretations provided by the ECG core lab. Three replicate 12-lead Holter ECGs were collected at -30, -15, and 0 minutes prior to the administration of study treatment on Days 1 (Baseline for placebo) and 3 (Baseline for lapatinib) and pre-dose and 1, 2, 3, 4, 6, 8, 10,12, and 24 hours post dose on Days 2 and 4. The three readings at each time point were averaged prior to any analysis. Baseline is the pre-dose ECGs (triplicate) taken on Day 1 for placebo and on Day 3 for lapatinib. |
| Number of Participants With the Worst-case Post-Baseline 12-lead Holter ECG Findings With Significant ST, T Wave, and U Wave Abnormalities | Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib. | Abnormal ECG findings or change in ECG morphological patterns were based on the ECG interpretations provided by the ECG core lab. Three replicate Holter ECGs were collected at 30, 15, and 0 minutes prior to the administration of study treatment on Days 1 (Baseline for placebo) and 3 (Baseline for lapatinib) and pre-dose and 1, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Days 2 and 4. The three readings at each time point were averaged prior to any analysis. Baseline is the pre-dose ECGs (triplicate) taken on Day 1 for placebo and Day 3 for lapatinib. The number of participants with the worst-case post-Baseline 12-lead Holter ECG findings with significant ST, T wave, and U wave abnormalities were analyzed. |
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | From the start of study treatment until follow-up (within approximately 28 days following the last dose of study medication [up to end of Study Week 4]) | An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as 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 or is a congenital anomaly/birth defect, or is an important medical eventsthat jeopardizes the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, new primary cancers, liver events, cardiac dysfunction, pneumonitis, and laboratory abnormalities. |
| Mean Albumin, and Hemoglobin at the Indicated Time Points | Baseline; Day 5 and end of study visit on Day 8-11 | Blood samples were collected for the measurement of albumin and hemoglobin at Baseline; Days 5 and 8-11. Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. |
| Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | Baseline; Day 5 and end of study visit on Day 8-11 | Blood samples were collected for the measurement of ALP, ALT, and AST at Baseline; Days 5 and 8-11. Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. |
| Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Baseline; Day 5 and end of study visit on Day 8-11 | Blood samples were collected for the measurement of direct bilirubin, total bilirubin, and creatinine at Baseline; Days 5 and 8-11; Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. |
| Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Baseline; Day 5 and end of study visit on Day 8-11 | Blood samples were collected for the measurement of calcium, chloride, CO2, potassium, sodium, magnesium and urea at Baseline; at Days 5 and 8-11. Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. |
| Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib. | A Holter monitor is an ambulatory portable device for continuously monitoring the cardiovascular system. Change from Baseline in QT interval, QTc interval, QTcB interval, QTcI interval, RR interval, PR interval, and QRS duration at each time point for lapatinib was assessed in comparison with time-matched placebo. Three replicate ECGs were collected at 30, 15, and 0 minutes prior to the administration of study treatment on Days 1 and 3 and pre-dose and 1, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Days 2 and 4. The three readings at each time point were averaged prior to any analysis. Baseline is the average of the pre-dose ECGs (triplicate) taken on Day 1 for placebo and Day 3 for lapatinib. Change from Baseline was calculated by subtracting the Baseline values from individual post-Baseline values for each time point. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post-dose) | Blood pressure measurements included SBP and DBP and were obtained at Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post dose). Baseline is defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Change From Baseline in Heart Rate at the Indicated Time Points | Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post dose | Heart rate were measured at Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post dose. Baseline is defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Number of Participants With 12-lead ECG Findings at Indicated Time Points | BL;Day 1 (at pre-dose);Day 2 (at pre-dose, 4, 8, 12 and 24 hr post dose);Day 4 (at pre-dose, 4, 8, 12 and 24 hr post dose);End of Study visit (Day 8-11); and Follow-up (within approx 28 days following last dose of study trt [up to end of Study Week 4]) | The number of participants with the 12-lead ECG findings normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) are reported. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee. A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at Baseline; on Day 1 (at pre-dose); on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post-last- dose); on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post-last-dose); at the End of Study visit (Day 8-11); and at the post-treatment Follow-up visit (if applicable). |
| Mean Area Under the Plasma Drug Concentration-time Curve (AUC) From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC[0-t]) and From Time Zero (Pre-dose) to 24 Hours Post Dose (AUC[0-24]) for Lapatinib | Day 1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-last-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-last-dose) | AUC is defined as the area under the lapatinib concentration-time curve as a measure of drug exposure. AUC(0-t) and AUC(0-24) were determined from the plasma concentration-time data using the linear trapezoidal rule for increased concentrations and the logarithmic trapezoidal rule for decreased concentrations. For PK analysis, one blood sample was collected on Day 1 for placebo Baseline. The 24 hour blood sample on Day 2 also served for lapatinib Baseline. Pre-dose blood samples were collected 30 minutes prior to the administration of study medication on Day 2 (placebo) and Day 4 (lapatinib). Serial blood samples were collected on Day 2 (for placebo) and on Day 4 (for lapatinib) at the following post-last-dose time points 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours. |
| Mean Maximum Plasma Concentration (Cmax) and Observed Plasma Concentration at 24 Hours Post-dose (C24) of Lapatinib | Day1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose) | The first occurrence of Cmax and C24 was determined directly from the raw concentration-time data. For PK analysis, one blood sample was collected on Day 1 for placebo Baseline. The 24 hour blood sample on Day 2 also served for lapatinib Baseline. Pre-dose blood samples were collected 30 minutes prior to the administration of study medication on Day 2 (placebo) and Day 4 (lapatinib). Serial blood samples were collected on Day 2 (for placebo) and on Day 4 (for lapatinib) at the following post-last-dose time points 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours. |
| Median Time to Cmax (Tmax) and the Time Prior to the First Quantifiable (Non-zero) Lapatinib Plasma Concentration (Tlag) Following the Last (3rd) Lapatinib Dose | Day 1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose) | For each participant, the time at which Cmax was observed (tmax) was determined directly from the raw concentration-time data. For each participant, the time prior to the first quantifiable (non-zero) concentration (tlag) was determined directly from the raw concentration-time data. Since all participants received 2 doses of study medication prior to the collection of the first (pre-dose) blood sample on Day 4, tlag was expected to be zero. For PK analysis, one blood sample was collected on Day 1 for placebo Baseline. The 24 hour blood sample on Day 2 also served for lapatinib Baseline. Pre-dose blood samples were collected 30 minutes prior to the administration of study medication on Day 2 (placebo) and Day 4 (lapatinib). Serial blood samples were collected on Day 2 (for placebo) and on Day 4 (for lapatinib) at the following post-last-dose time points 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours. |
| Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | Baseline; Day 5 and end of study visit on Day 8-11 | Blood samples were collected for the measurement of total neutrophils (ANC), platelets, and leukocyte count at Baseline; Days 5 and 8-11. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. |
Countries
United States
Participant flow
Pre-assignment details
All participants (par.) underwent screening assessments within 14 days prior to the start of study treatment to determine their eligibility for enrollment. Study treatment was administered over a period of 5 days, and an End of Study visit was conducted on Day 8-11.
Participants by arm
| Arm | Count |
|---|---|
| Placebo and Lapatinib 2000 mg Participants received three doses of matching placebo in the morning and evening on Day 1 and in the morning on Day 2. Participants then received three doses of lapatinib 2000 mg (250 mg x 8 tablets/dose) in the morning and evening on Day 3 and in the morning on Day 4. | 58 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Lapatinib on Day 3 and Day 4 (2 Days) | Adverse Event | 0 | 2 |
| Lapatinib on Day 3 and Day 4 (2 Days) | Physician Decision | 0 | 1 |
| Lapatinib on Day 3 and Day 4 (2 Days) | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo and Lapatinib 2000 mg |
|---|---|
| Age, Continuous | 55.1 Years STANDARD_DEVIATION 12.3 |
| Race/Ethnicity, Customized African American/African Heritage | 3 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized missing | 2 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 51 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 57 | 44 / 58 |
| serious Total, serious adverse events | 0 / 57 | 4 / 58 |
Outcome results
Primary
Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg
A Holter monitor is an ambulatory portable device used for continuously monitoring the cardiovascular system. Three replicate electrocardiograms (ECGs) were collected at 30, 15, and 0 minutes prior to the administration of study treatment (trt) on Days 1 and 3 and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 2 and 4. The 3 readings at each time point (TP) were averaged prior to any analysis. BL is the average of the pre-dose QTcF values (triplicate) taken on Day 1 for PBO and on Day 3 for LAP. Mean change from BL was calculated by subtracting the BL values from individual QTcF for each TP. BL adjusted mean difference in absolute QTcF between LAB and PBO (trt difference) with the corresponding 90% confidence interval (CI) was estimated for each TP (pre-dose and 1, 2, 3, 4, 6, 8, 10, 12, and 24-hr post-dose). Trt difference analysis was performed by a repeated measures analysis of variance adjusted for trt group, TP, and trt group\*TP interaction.
Time frame: Baseline (BL) (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours (hr) post-dose on Day 2 for placebo (PBO). Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib (LAP).
Population: Evaluable Population: all participants in the All-Treated Subjects (ATS) Population who met the criteria for dosing compliance, ECG acquisition, and Baseline ECG acquisition. The ATS Population is comprised of all participants who received at least one dose of study medication (placebo or lapatinib).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 10 hour | -4.53 Milliseconds | Standard Error 1.98 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | Pre-dose | -3.71 Milliseconds | Standard Error 1.53 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 1 hour | 0.66 Milliseconds | Standard Error 1.46 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 2 hour | 0.49 Milliseconds | Standard Error 1.23 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 4 hour | 3.18 Milliseconds | Standard Error 1.73 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 6 hour | -4.50 Milliseconds | Standard Error 1.82 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 8 hour | -5.09 Milliseconds | Standard Error 1.93 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 12 hour | -1.49 Milliseconds | Standard Error 1.96 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 24 hour | -1.25 Milliseconds | Standard Error 1.52 |
| Placebo | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 3 hour | 2.78 Milliseconds | Standard Error 1.48 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 24 hour | 2.51 Milliseconds | Standard Error 1.55 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 3 hour | 9.19 Milliseconds | Standard Error 1.48 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 6 hour | 1.36 Milliseconds | Standard Error 1.83 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | Pre-dose | 2.60 Milliseconds | Standard Error 1.53 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 12 hour | 4.27 Milliseconds | Standard Error 1.96 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 1 hour | 7.09 Milliseconds | Standard Error 1.47 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 8 hour | -0.18 Milliseconds | Standard Error 1.95 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 2 hour | 8.20 Milliseconds | Standard Error 1.24 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 10 hour | 4.22 Milliseconds | Standard Error 1.99 |
| Lapatinib 2000 mg | Treatment Difference in Duration of Cardiac Ventricular Depolarization and Repolarization Interval (QT) in Fridericia-corrected QT Interval (QTcF) Values Between Placebo and Lapatinib 2000mg | 4 hour | 9.78 Milliseconds | Standard Error 1.73 |
90% CI: [2.72, 9.89]
90% CI: [3, 9.87]
90% CI: [4.82, 10.6]
90% CI: [2.94, 9.89]
90% CI: [2.54, 10.65]
90% CI: [1.57, 10.14]
90% CI: [0.35, 9.47]
90% CI: [4.08, 13.42]
90% CI: [1.16, 10.36]
90% CI: [0.15, 7.36]
Secondary
Change From Baseline in Heart Rate at the Indicated Time Points
Heart rate were measured at Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post dose. Baseline is defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post dose
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 4-12 hour post dose, n=54 | 3.2 Beats per minute | Standard Deviation 11.09 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 4-24 hour post dose, n=54 | 1.8 Beats per minute | Standard Deviation 8.75 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 2-Pre dose, n=57 | 3.9 Beats per minute | Standard Deviation 9.82 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 2-4 hour post dose, n=58 | -1.7 Beats per minute | Standard Deviation 9.1 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 2-8 hour post dose, n=58 | 3.2 Beats per minute | Standard Deviation 9.96 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 2-12 hour post dose, n=58 | 3.3 Beats per minute | Standard Deviation 10.02 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 2-24 hour post dose, n=58 | 0.8 Beats per minute | Standard Deviation 9.78 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 4-Pre dose, n=56 | 3.5 Beats per minute | Standard Deviation 10.88 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 4-4 hour post dose, n=55 | -2.0 Beats per minute | Standard Deviation 10.89 |
| Placebo | Change From Baseline in Heart Rate at the Indicated Time Points | Day 4-8 hour post dose, n=55 | 2.5 Beats per minute | Standard Deviation 11.12 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
Blood pressure measurements included SBP and DBP and were obtained at Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post dose). Baseline is defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post-dose)
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 2-12 hour post dose), n=58 | -4.2 Millimeter of mercury (mmHg) | Standard Deviation 14.62 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 2-24 hour post dose), n=58 | -2.2 Millimeter of mercury (mmHg) | Standard Deviation 11.29 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 4-Pre dose), n=56 | -9.4 Millimeter of mercury (mmHg) | Standard Deviation 14.55 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 4-4 hour post dose), n=55 | -8.7 Millimeter of mercury (mmHg) | Standard Deviation 12.75 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 4-8 hour post dose), n=55 | -8.3 Millimeter of mercury (mmHg) | Standard Deviation 14.15 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 4-12 hour post dose), n=54 | -8.8 Millimeter of mercury (mmHg) | Standard Deviation 13.26 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 4-24 hour post dose), n=54 | -4.8 Millimeter of mercury (mmHg) | Standard Deviation 11.54 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 2-Pre dose), n=58 | -4.2 Millimeter of mercury (mmHg) | Standard Deviation 8.34 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 4-12 hour post dose), n=54 | -8.1 Millimeter of mercury (mmHg) | Standard Deviation 9.29 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 4-24 hour post dose), n=54 | -5.0 Millimeter of mercury (mmHg) | Standard Deviation 8.14 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 2-4 hour post dose), n=58 | -4.6 Millimeter of mercury (mmHg) | Standard Deviation 8.13 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 2-8 hour post dose), n=58 | -8.2 Millimeter of mercury (mmHg) | Standard Deviation 9.13 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 2-12 hour post dose), n=58 | -6.3 Millimeter of mercury (mmHg) | Standard Deviation 8.77 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 2-24 hour post dose), n=58 | -2.9 Millimeter of mercury (mmHg) | Standard Deviation 7.27 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 4-Pre dose), n=56 | -8.6 Millimeter of mercury (mmHg) | Standard Deviation 8.06 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 4-4 hour post dose), n=55 | -7.3 Millimeter of mercury (mmHg) | Standard Deviation 8.49 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Diastolic BP (Day 4-8 hour post dose), n=55 | -7.4 Millimeter of mercury (mmHg) | Standard Deviation 10.12 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 2-Pre dose), n=58 | -3.5 Millimeter of mercury (mmHg) | Standard Deviation 13.19 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 2-4 hour post dose), n=58 | -2.1 Millimeter of mercury (mmHg) | Standard Deviation 13.21 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points | Systolic BP (Day 2-8 hour post dose), n=58 | -7.0 Millimeter of mercury (mmHg) | Standard Deviation 13.71 |
Secondary
Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points
A Holter monitor is an ambulatory portable device for continuously monitoring the cardiovascular system. Change from Baseline in QT interval, QTc interval, QTcB interval, QTcI interval, RR interval, PR interval, and QRS duration at each time point for lapatinib was assessed in comparison with time-matched placebo. Three replicate ECGs were collected at 30, 15, and 0 minutes prior to the administration of study treatment on Days 1 and 3 and pre-dose and 1, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Days 2 and 4. The three readings at each time point were averaged prior to any analysis. Baseline is the average of the pre-dose ECGs (triplicate) taken on Day 1 for placebo and Day 3 for lapatinib. Change from Baseline was calculated by subtracting the Baseline values from individual post-Baseline values for each time point.
Time frame: Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib.
Population: Evaluable Population. Only participants available at the specified time point (represented as n=X, X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (predose), n=37, 37 | -6.40 Milliseconds | Standard Deviation 13.133 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (1 hour), n=37, 37 | -1.45 Milliseconds | Standard Deviation 10.925 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (2 hour), n=37, 37 | -1.40 Milliseconds | Standard Deviation 12.037 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (3 hour), n=37, 37 | -0.05 Milliseconds | Standard Deviation 12.015 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (6 hour), n=37, 36 | -11.53 Milliseconds | Standard Deviation 15.688 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (predose), n=37, 37 | -6.24 Milliseconds | Standard Deviation 16.788 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (1 hour), n=37, 37 | 0.10 Milliseconds | Standard Deviation 15.32 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (2 hour), n=37, 37 | 1.24 Milliseconds | Standard Deviation 15.055 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (3 hour), n=37, 37 | 2.14 Milliseconds | Standard Deviation 14.798 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (4 hour), n=37, 37 | 1.14 Milliseconds | Standard Deviation 16.741 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (6 hour), n=37, 36 | -17.77 Milliseconds | Standard Deviation 21.24 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (8 hour), n=37, 36 | -13.51 Milliseconds | Standard Deviation 20.997 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (10 hour), n=37, 37 | -15.99 Milliseconds | Standard Deviation 19.617 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (12 hour), n=37, 37 | -11.28 Milliseconds | Standard Deviation 18.576 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTc B interval (1 hour), n=37, 37 | 1.07 Milliseconds | Standard Deviation 8.061 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (2 hour), n=37, 37 | 0.11 Milliseconds | Standard Deviation 8.918 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (3 hour), n=37, 37 | 3.13 Milliseconds | Standard Deviation 8.954 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (4 hour), n=37, 37 | 4.38 Milliseconds | Standard Deviation 10.786 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (6 hour), n=37, 36 | 3.11 Milliseconds | Standard Deviation 10.275 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (8 hour), n=37, 36 | -0.29 Milliseconds | Standard Deviation 11.117 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (10 hour), n=37, 37 | 1.93 Milliseconds | Standard Deviation 9.871 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (12 hour), n=37, 37 | 4.21 Milliseconds | Standard Deviation 10.238 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (predose), n=37, 37 | -19.19 Milliseconds | Standard Deviation 78.141 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (1 hour), n=37, 37 | -5.38 Milliseconds | Standard Deviation 65.333 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (2 hour), n=37, 37 | 2.71 Milliseconds | Standard Deviation 72.996 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (3 hour), n=37, 37 | -5.38 Milliseconds | Standard Deviation 67.323 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (6 hour), n=37, 36 | -85.20 Milliseconds | Standard Deviation 93.003 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (8 hour), n=37, 36 | -54.95 Milliseconds | Standard Deviation 92.426 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (12 hour), n=37, 37 | -63.20 Milliseconds | Standard Deviation 79.552 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (24 hour), n=37, 35 | -19.69 Milliseconds | Standard Deviation 67.199 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (predose), n=37, 37 | -1.87 Milliseconds | Standard Deviation 9.162 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (1 hour), n=37, 37 | -0.20 Milliseconds | Standard Deviation 7.026 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (2 hour), n=37, 37 | 0.90 Milliseconds | Standard Deviation 6.563 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (3 hour), n=37, 37 | 0.25 Milliseconds | Standard Deviation 7.839 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (4 hour), n=37, 37 | -0.40 Milliseconds | Standard Deviation 7.321 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (6 hour), n=37, 36 | -3.05 Milliseconds | Standard Deviation 9.165 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (8 hour), n=37, 36 | -2.72 Milliseconds | Standard Deviation 6.993 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (10 hour), n=37, 37 | -4.77 Milliseconds | Standard Deviation 6.892 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (12 hour), n=37, 37 | -2.97 Milliseconds | Standard Deviation 7.071 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (24 hour), n=37, 35 | -1.61 Milliseconds | Standard Deviation 7.433 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (predose), n=37, 37 | 0.88 Milliseconds | Standard Deviation 3.562 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (1 hour), n=37, 37 | 1.45 Milliseconds | Standard Deviation 3.766 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (2 hour), n=37, 37 | 1.08 Milliseconds | Standard Deviation 3.29 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (3 hour), n=37, 37 | 0.89 Milliseconds | Standard Deviation 3.896 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (6 hour), n=37, 36 | 0.88 Milliseconds | Standard Deviation 3.839 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (8 hour), n=37, 36 | 0.80 Milliseconds | Standard Deviation 3.5 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (12 hour), n=37, 37 | 0.13 Milliseconds | Standard Deviation 3.634 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (24 hour), n=37, 35 | 1.07 Milliseconds | Standard Deviation 3.89 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (24 hour), n=37, 35 | -4.10 Milliseconds | Standard Deviation 15.152 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (4 hour), n=37, 37 | 0.32 Milliseconds | Standard Deviation 13.786 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (8 hour), n=37, 36 | -10.13 Milliseconds | Standard Deviation 14.223 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (10 hour), n=37, 37 | -11.70 Milliseconds | Standard Deviation 16.374 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (12 hour), n=37, 37 | -6.22 Milliseconds | Standard Deviation 17.752 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (24 hour), n=37, 35 | -4.71 Milliseconds | Standard Deviation 9.677 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (predose), n=37, 37 | -2.18 Milliseconds | Standard Deviation 10.942 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (24 hour), n=37, 35 | 0.42 Milliseconds | Standard Deviation 8.756 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (4 hour), n=37, 37 | -13.43 Milliseconds | Standard Deviation 64.043 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (10 hour), n=37, 37 | -74.17 Milliseconds | Standard Deviation 82.639 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (4 hour), n=37, 37 | 1.17 Milliseconds | Standard Deviation 3.612 |
| Placebo | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (10 hour), n=37, 37 | 0.70 Milliseconds | Standard Deviation 3.574 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (24 hour), n=37, 35 | -17.15 Milliseconds | Standard Deviation 69.927 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (predose), n=37, 37 | 2.24 Milliseconds | Standard Deviation 12.93 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (10 hour), n=37, 37 | 1.48 Milliseconds | Standard Deviation 5.042 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (1 hour), n=37, 37 | 6.00 Milliseconds | Standard Deviation 13.053 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (predose), n=37, 37 | 3.48 Milliseconds | Standard Deviation 6 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (2 hour), n=37, 37 | 8.42 Milliseconds | Standard Deviation 13.054 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (1 hour), n=37, 37 | 4.90 Milliseconds | Standard Deviation 8.492 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (12 hour), n=37, 37 | 1.92 Milliseconds | Standard Deviation 3.992 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (6 hour), n=37, 36 | -3.86 Milliseconds | Standard Deviation 14.987 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (2 hour), n=37, 37 | 4.98 Milliseconds | Standard Deviation 8.952 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (predose), n=37, 37 | 1.05 Milliseconds | Standard Deviation 17.033 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (predose), n=37, 37 | 4.07 Milliseconds | Standard Deviation 9.271 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (1 hour), n=37, 37 | 7.69 Milliseconds | Standard Deviation 18.87 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (3 hour), n=37, 37 | 4.86 Milliseconds | Standard Deviation 7.668 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (2 hour), n=37, 37 | 10.66 Milliseconds | Standard Deviation 16.315 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (24 hour), n=37, 35 | 0.97 Milliseconds | Standard Deviation 3.461 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (3 hour), n=37, 37 | 11.09 Milliseconds | Standard Deviation 18.805 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (8 hour), n=37, 36 | 3.97 Milliseconds | Standard Deviation 10.481 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (4 hour), n=37, 37 | 10.09 Milliseconds | Standard Deviation 20.062 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (6 hour), n=37, 36 | 0.32 Milliseconds | Standard Deviation 8.815 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (6 hour), n=37, 36 | -6.97 Milliseconds | Standard Deviation 20.888 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (24 hour), n=37, 35 | 0.54 Milliseconds | Standard Deviation 17.928 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (8 hour), n=37, 36 | -6.88 Milliseconds | Standard Deviation 25.718 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (8 hour), n=37, 36 | 0.10 Milliseconds | Standard Deviation 9.325 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (8 hour), n=37, 36 | -4.65 Milliseconds | Standard Deviation 17.336 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (12 hour), n=37, 37 | 0.35 Milliseconds | Standard Deviation 15.458 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (10 hour), n=37, 37 | -3.68 Milliseconds | Standard Deviation 21.191 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (3 hour), n=37, 37 | 8.76 Milliseconds | Standard Deviation 14.227 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QT interval (12 hour), n=37, 37 | -1.58 Milliseconds | Standard Deviation 21.615 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (10 hour), n=37, 37 | -0.23 Milliseconds | Standard Deviation 8.743 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTc B interval (1 hour), n=37, 37 | 7.37 Milliseconds | Standard Deviation 8.978 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (12 hour), n=37, 37 | 8.08 Milliseconds | Standard Deviation 11.379 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (2 hour), n=37, 37 | 7.43 Milliseconds | Standard Deviation 8.626 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (12 hour), n=37, 37 | 1.81 Milliseconds | Standard Deviation 9.503 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (3 hour), n=37, 37 | 8.77 Milliseconds | Standard Deviation 8.846 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (4 hour), n=37, 37 | 8.00 Milliseconds | Standard Deviation 15.274 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (4 hour), n=37, 37 | 10.14 Milliseconds | Standard Deviation 9.334 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (24 hour), n=37, 35 | 0.94 Milliseconds | Standard Deviation 6.388 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (6 hour), n=37, 36 | 7.08 Milliseconds | Standard Deviation 12.382 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | PR interval (4 hour), n=37, 37 | 4.05 Milliseconds | Standard Deviation 7.713 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (3 hour), n=37, 37 | 12.50 Milliseconds | Standard Deviation 67.526 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (10 hour), n=37, 37 | 9.25 Milliseconds | Standard Deviation 13.06 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (10 hour), n=37, 37 | -0.26 Milliseconds | Standard Deviation 16.461 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcB interval (24 hour), n=37, 35 | 5.38 Milliseconds | Standard Deviation 7.752 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (2 hour), n=37, 37 | 0.66 Milliseconds | Standard Deviation 3.851 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (predose), n=37, 37 | -9.68 Milliseconds | Standard Deviation 74.332 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (predose), n=37, 37 | 0.46 Milliseconds | Standard Deviation 3.86 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (1 hour), n=37, 37 | 3.14 Milliseconds | Standard Deviation 78.012 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (3 hour), n=37, 37 | 1.03 Milliseconds | Standard Deviation 4.786 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (2 hour), n=37, 37 | 16.07 Milliseconds | Standard Deviation 63.665 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (4 hour), n=37, 37 | 1.83 Milliseconds | Standard Deviation 4.617 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (4 hour), n=37, 37 | 2.90 Milliseconds | Standard Deviation 78.299 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (1 hour), n=37, 37 | 0.67 Milliseconds | Standard Deviation 4.164 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (6 hour), n=37, 36 | -61.77 Milliseconds | Standard Deviation 83.279 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (6 hour), n=37, 36 | 1.65 Milliseconds | Standard Deviation 4.212 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (8 hour), n=37, 36 | -41.60 Milliseconds | Standard Deviation 90.545 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (10 hour), n=37, 37 | -49.38 Milliseconds | Standard Deviation 75.999 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QTcI interval (24 hour), n=37, 35 | 2.03 Milliseconds | Standard Deviation 13.715 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | RR interval (12 hour), n=37, 37 | -38.38 Milliseconds | Standard Deviation 74.737 |
| Lapatinib 2000 mg | Change From Baseline in the Holter ECG Parameters of QT Interval, Corrected QT Interval (QTc), Bazett Corrected QTc Interval (QTcB), Individual-corrected QT Interval (QTcI), RR Interval, PR Interval, and QRS Duration at Indicated Time Points | QRS interval (8 hour), n=37, 36 | 1.47 Milliseconds | Standard Deviation 5.417 |
Secondary
Mean Albumin, and Hemoglobin at the Indicated Time Points
Blood samples were collected for the measurement of albumin and hemoglobin at Baseline; Days 5 and 8-11. Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date.
Time frame: Baseline; Day 5 and end of study visit on Day 8-11
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Albumin, and Hemoglobin at the Indicated Time Points | Albumin (Baseline), n=58 | 38.8 Grams per liter (g/L) | Standard Deviation 3.83 |
| Placebo | Mean Albumin, and Hemoglobin at the Indicated Time Points | Albumin (Day 5), n=49 | 35.5 Grams per liter (g/L) | Standard Deviation 4.42 |
| Placebo | Mean Albumin, and Hemoglobin at the Indicated Time Points | Albumin (Day 8-11), n=55 | 37.5 Grams per liter (g/L) | Standard Deviation 3.94 |
| Placebo | Mean Albumin, and Hemoglobin at the Indicated Time Points | Hemoglobin (Day 5), n=48 | 114.8 Grams per liter (g/L) | Standard Deviation 15.63 |
| Placebo | Mean Albumin, and Hemoglobin at the Indicated Time Points | Hemoglobin (Day 8-11), n=55 | 117.6 Grams per liter (g/L) | Standard Deviation 15.51 |
| Placebo | Mean Albumin, and Hemoglobin at the Indicated Time Points | Hemoglobin (Baseline), n=58 | 123.7 Grams per liter (g/L) | Standard Deviation 15.45 |
Secondary
Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points
Blood samples were collected for the measurement of ALP, ALT, and AST at Baseline; Days 5 and 8-11. Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date.
Time frame: Baseline; Day 5 and end of study visit on Day 8-11
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | ALP (baseline), n=58 | 116.9 International units per liter (IU/L) | Standard Deviation 90.91 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | ALT (Day 8-11), n=55 | 24.2 International units per liter (IU/L) | Standard Deviation 16.98 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | AST (baseline), n=58 | 29.7 International units per liter (IU/L) | Standard Deviation 16.09 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | ALP (Day 5), n=49 | 111.2 International units per liter (IU/L) | Standard Deviation 97.55 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | ALP (Day 8-11), n=55 | 116.7 International units per liter (IU/L) | Standard Deviation 107.5 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | ALT (baseline), n=58 | 25.9 International units per liter (IU/L) | Standard Deviation 17.09 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | ALT (Day 5), n=49 | 23.1 International units per liter (IU/L) | Standard Deviation 14.85 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | AST (Day 5), n=48 | 26.9 International units per liter (IU/L) | Standard Deviation 14.16 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) at the Indicated Time Points | AST (Day 8-11), n=55 | 30.3 International units per liter (IU/L) | Standard Deviation 16.46 |
Secondary
Mean Area Under the Plasma Drug Concentration-time Curve (AUC) From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC[0-t]) and From Time Zero (Pre-dose) to 24 Hours Post Dose (AUC[0-24]) for Lapatinib
AUC is defined as the area under the lapatinib concentration-time curve as a measure of drug exposure. AUC(0-t) and AUC(0-24) were determined from the plasma concentration-time data using the linear trapezoidal rule for increased concentrations and the logarithmic trapezoidal rule for decreased concentrations. For PK analysis, one blood sample was collected on Day 1 for placebo Baseline. The 24 hour blood sample on Day 2 also served for lapatinib Baseline. Pre-dose blood samples were collected 30 minutes prior to the administration of study medication on Day 2 (placebo) and Day 4 (lapatinib). Serial blood samples were collected on Day 2 (for placebo) and on Day 4 (for lapatinib) at the following post-last-dose time points 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours.
Time frame: Day 1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-last-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-last-dose)
Population: Pharmacokinetic (PK) Population: all participants in the ATS Population for whom at least one PK sample was obtained and analyzed. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Area Under the Plasma Drug Concentration-time Curve (AUC) From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC[0-t]) and From Time Zero (Pre-dose) to 24 Hours Post Dose (AUC[0-24]) for Lapatinib | AUC[0-t]), n=56 | 56000 Nanograms hour per milliliter | Geometric Coefficient of Variation 73.4 |
| Placebo | Mean Area Under the Plasma Drug Concentration-time Curve (AUC) From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC[0-t]) and From Time Zero (Pre-dose) to 24 Hours Post Dose (AUC[0-24]) for Lapatinib | AUC[0-24]), n=54 | 59200 Nanograms hour per milliliter | Geometric Coefficient of Variation 60.2 |
Secondary
Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points
Blood samples were collected for the measurement of calcium, chloride, CO2, potassium, sodium, magnesium and urea at Baseline; at Days 5 and 8-11. Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date.
Time frame: Baseline; Day 5 and end of study visit on Day 8-11
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Potassium (Day 8-11), n=55 | 3.98 Millimoles per liter (mmol/L) | Standard Deviation 0.372 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Sodium (Baseline), n=58 | 138.8 Millimoles per liter (mmol/L) | Standard Deviation 2.42 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Sodium (Day 5), n=49 | 138.5 Millimoles per liter (mmol/L) | Standard Deviation 2.34 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Sodium (Day 8-11), n=55 | 139.0 Millimoles per liter (mmol/L) | Standard Deviation 2.55 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Calcium (Baseline), n=57 | 2.344 Millimoles per liter (mmol/L) | Standard Deviation 0.1176 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Calcium (Day 5), n=49 | 2.231 Millimoles per liter (mmol/L) | Standard Deviation 0.1148 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Calcium (Day 8-11), n=55 | 2.303 Millimoles per liter (mmol/L) | Standard Deviation 0.1336 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Chloride (Baseline), n=58 | 103.6 Millimoles per liter (mmol/L) | Standard Deviation 3.42 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Chloride (Day 5), n=49 | 104.4 Millimoles per liter (mmol/L) | Standard Deviation 2.76 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Chloride (Day 8-11), n=55 | 104.7 Millimoles per liter (mmol/L) | Standard Deviation 3.03 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | CO2 (Baseline), n=57 | 26.965 Millimoles per liter (mmol/L) | Standard Deviation 2.7449 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | CO2 (Day 5), n=49 | 26.053 Millimoles per liter (mmol/L) | Standard Deviation 3.1032 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | CO2 (Day 8-11), n=55 | 26.345 Millimoles per liter (mmol/L) | Standard Deviation 2.939 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Potassium (Baseline), n=58 | 4.05 Millimoles per liter (mmol/L) | Standard Deviation 0.337 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Potassium (Day 5), n=49 | 3.84 Millimoles per liter (mmol/L) | Standard Deviation 0.425 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Magnesium (Baseline), n=58 | 0.835 Millimoles per liter (mmol/L) | Standard Deviation 0.0906 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Magnesium (Day 5, n=49) | 0.769 Millimoles per liter (mmol/L) | Standard Deviation 0.142 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Magnesium (Day 8-11), n=55 | 0.795 Millimoles per liter (mmol/L) | Standard Deviation 0.1088 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Urea (Baseline), n=58 | 5.273 Millimoles per liter (mmol/L) | Standard Deviation 1.9485 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Urea (Day 5), n=49 | 5.078 Millimoles per liter (mmol/L) | Standard Deviation 1.7032 |
| Placebo | Mean Calcium, Chloride, Carbon Dioxide (CO2), Potassium, Sodium, Magnesium and Urea at the Indicated Time Points | Urea (Day 8-11), n=55 | 5.095 Millimoles per liter (mmol/L) | Standard Deviation 1.7922 |
Secondary
Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points
Blood samples were collected for the measurement of direct bilirubin, total bilirubin, and creatinine at Baseline; Days 5 and 8-11; Baseline is defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date.
Time frame: Baseline; Day 5 and end of study visit on Day 8-11
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Direct Bilirubin (Baseline), n=58 | 2.683 Micromoles per liter (µmol/L) | Standard Deviation 1.6678 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Direct Bilirubin (Day 5), n=46 | 3.123 Micromoles per liter (µmol/L) | Standard Deviation 2.049 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Direct Bilirubin (Day 8-11), n=54 | 2.502 Micromoles per liter (µmol/L) | Standard Deviation 1.4749 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Bilirubin (Baseline), n=58 | 10.496 Micromoles per liter (µmol/L) | Standard Deviation 4.362 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Bilirubin (Day 5), n=49 | 13.450 Micromoles per liter (µmol/L) | Standard Deviation 6.2571 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Bilirubin (Day 8-11), n=55 | 9.980 Micromoles per liter (µmol/L) | Standard Deviation 4.8786 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Creatinine (Baseline), n=58 | 73.448 Micromoles per liter (µmol/L) | Standard Deviation 23.6266 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Creatinine (Day 5), n=49 | 77.124 Micromoles per liter (µmol/L) | Standard Deviation 27.9006 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, and Creatinine at the Indicated Time Points | Creatinine (Day 8-11), n=55 | 74.192 Micromoles per liter (µmol/L) | Standard Deviation 25.0945 |
Secondary
Mean Maximum Plasma Concentration (Cmax) and Observed Plasma Concentration at 24 Hours Post-dose (C24) of Lapatinib
The first occurrence of Cmax and C24 was determined directly from the raw concentration-time data. For PK analysis, one blood sample was collected on Day 1 for placebo Baseline. The 24 hour blood sample on Day 2 also served for lapatinib Baseline. Pre-dose blood samples were collected 30 minutes prior to the administration of study medication on Day 2 (placebo) and Day 4 (lapatinib). Serial blood samples were collected on Day 2 (for placebo) and on Day 4 (for lapatinib) at the following post-last-dose time points 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours.
Time frame: Day1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose)
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Maximum Plasma Concentration (Cmax) and Observed Plasma Concentration at 24 Hours Post-dose (C24) of Lapatinib | Cmax, n=56 | 3920 Nanograms per mL | Geometric Coefficient of Variation 50.8 |
| Placebo | Mean Maximum Plasma Concentration (Cmax) and Observed Plasma Concentration at 24 Hours Post-dose (C24) of Lapatinib | C24, n=54 | 1410 Nanograms per mL | Geometric Coefficient of Variation 88.1 |
Secondary
Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points
Blood samples were collected for the measurement of total neutrophils (ANC), platelets, and leukocyte count at Baseline; Days 5 and 8-11. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date.
Time frame: Baseline; Day 5 and end of study visit on Day 8-11
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | ANC (Baseline), n=58 | 23.959 10^9 cells per liter (GI/L) | Standard Deviation 30.019 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | ANC (Day 5), n=48 | 25.802 10^9 cells per liter (GI/L) | Standard Deviation 30.8866 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | ANC (Day 8-11), n=55 | 23.848 10^9 cells per liter (GI/L) | Standard Deviation 29.8574 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | Platelets (Baseline), n=58 | 262.6 10^9 cells per liter (GI/L) | Standard Deviation 90.29 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | Platelets (Day 5), n=48 | 239.3 10^9 cells per liter (GI/L) | Standard Deviation 86.9 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | Platelets (Day 8-11), n=55 | 263.7 10^9 cells per liter (GI/L) | Standard Deviation 92.44 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | Leukocytes (Baseline), n=58 | 6.686 10^9 cells per liter (GI/L) | Standard Deviation 2.5192 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | Leukocytes (Day 5), n=48 | 6.227 10^9 cells per liter (GI/L) | Standard Deviation 2.3865 |
| Placebo | Mean Total Neutrophils (ANC [Absolute Neutrophil Count]), Platelets and Leukocyte Count at the Indicated Time Points | Leukocytes (Day 8-11), n=55 | 7.198 10^9 cells per liter (GI/L) | Standard Deviation 3.6319 |
Secondary
Median Time to Cmax (Tmax) and the Time Prior to the First Quantifiable (Non-zero) Lapatinib Plasma Concentration (Tlag) Following the Last (3rd) Lapatinib Dose
For each participant, the time at which Cmax was observed (tmax) was determined directly from the raw concentration-time data. For each participant, the time prior to the first quantifiable (non-zero) concentration (tlag) was determined directly from the raw concentration-time data. Since all participants received 2 doses of study medication prior to the collection of the first (pre-dose) blood sample on Day 4, tlag was expected to be zero. For PK analysis, one blood sample was collected on Day 1 for placebo Baseline. The 24 hour blood sample on Day 2 also served for lapatinib Baseline. Pre-dose blood samples were collected 30 minutes prior to the administration of study medication on Day 2 (placebo) and Day 4 (lapatinib). Serial blood samples were collected on Day 2 (for placebo) and on Day 4 (for lapatinib) at the following post-last-dose time points 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours.
Time frame: Day 1 pre-dose; on Day 2 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose), and on Day 4 (at pre-dose, then 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose)
Population: PK Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Median Time to Cmax (Tmax) and the Time Prior to the First Quantifiable (Non-zero) Lapatinib Plasma Concentration (Tlag) Following the Last (3rd) Lapatinib Dose | tmax | 3.55 Hours |
| Placebo | Median Time to Cmax (Tmax) and the Time Prior to the First Quantifiable (Non-zero) Lapatinib Plasma Concentration (Tlag) Following the Last (3rd) Lapatinib Dose | tlag | 0 Hours |
Secondary
Number of Participants With 12-lead ECG Findings at Indicated Time Points
The number of participants with the 12-lead ECG findings normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) are reported. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee. A single safety 12-lead ECG was performed using a standard 12-lead ECG machine at Baseline; on Day 1 (at pre-dose); on Day 2 (at pre-dose, 4, 8, 12 and 24 hours post-last- dose); on Day 4 (at pre-dose, 4, 8, 12 and 24 hours post-last-dose); at the End of Study visit (Day 8-11); and at the post-treatment Follow-up visit (if applicable).
Time frame: BL;Day 1 (at pre-dose);Day 2 (at pre-dose, 4, 8, 12 and 24 hr post dose);Day 4 (at pre-dose, 4, 8, 12 and 24 hr post dose);End of Study visit (Day 8-11); and Follow-up (within approx 28 days following last dose of study trt [up to end of Study Week 4])
Population: ATS Population. Only participants available at the specified time point (represented as n=X in the category title) were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Baseline (Abn CS), n=58 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 1 (NL), n=58 | 35 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 1 (Abn NCS), n=58 | 23 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 1 (Abn CS), n=58 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (Pre dose) (NL), n=58 | 32 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (Pre dose) (Abn NCS), n=58 | 26 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (Pre dose) (Abn CS), n=58 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (4 hours post dose) (NL), n=58 | 34 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (4 hours post dose) (Abn NCS), n=58 | 24 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (4 hours post dose) (Abn CS), n=58 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (8 hours post dose) (NL), n=58 | 30 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (8 hours post dose) (Abn NCS), n=58 | 28 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (8 hours post dose) (Abn CS), n=58 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (12 hours post dose) (NL), n=58 | 31 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (12 hours post dose) (Abn NCS), n=58 | 27 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (12 hours post dose) (Abn CS), n=58 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (24 hours post dose) (NL), n=58 | 34 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (24 hours post dose) (Abn NCS), n=58 | 24 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 2 (24 hours post dose) (Abn CS), n=58 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (Pre dose) (NL), n=56 | 31 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (Pre dose) (Abn NCS), n=56 | 25 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (Pre dose) (Abn CS), n=56 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (4 hours post dose) (NL), n=55 | 26 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (4 hours post dose) (Abn NCS), n=55 | 29 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (4 hours post dose) (Abn CS), n=55 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (8 hours post dose) (NL), n=55 | 25 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (8 hours post dose) (Abn NCS), n=55 | 30 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (8 hours post dose) (Abn CS), n=55 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (12 hours post dose) (NL), n=55 | 27 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (12 hours post dose) (Abn NCS), n=55 | 28 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (12 hours post dose) (Abn CS), n=55 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (24 hours post dose) (NL), n=54 | 28 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (24 hours post dose) (Abn NCS), n=54 | 26 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 4 (24 hours post dose) (Abn CS), n=54 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 8-11 (NL), n=50 | 29 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 8-11 (Abn CS), n=50 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Follow-up (NL), n=2 | 1 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Follow-up (Abn NCS), n=2 | 1 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Follow-up (Abn CS), n=2 | 0 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Baseline (NL), n=58 | 36 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Baseline (Abn NCS), n=58 | 22 Participants |
| Placebo | Number of Participants With 12-lead ECG Findings at Indicated Time Points | Day 8-11 (Abn NCS), n=50 | 21 Participants |
Secondary
Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points
The number of participants with 12-lead Holter ECG findings of normal (NL), abnormal not clinically significant (Abn NCS), and abnormal clinically significant (Abn CS) are reported. Abnormal ECG findings or change in ECG morphological patterns were based on the ECG interpretations provided by the ECG core lab. Three replicate 12-lead Holter ECGs were collected at -30, -15, and 0 minutes prior to the administration of study treatment on Days 1 (Baseline for placebo) and 3 (Baseline for lapatinib) and pre-dose and 1, 2, 3, 4, 6, 8, 10,12, and 24 hours post dose on Days 2 and 4. The three readings at each time point were averaged prior to any analysis. Baseline is the pre-dose ECGs (triplicate) taken on Day 1 for placebo and on Day 3 for lapatinib.
Time frame: Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib.
Population: Evaluable Population. Only participants available at the specified time point (represented as n=X, X in the category title) were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -30 minutes (NL), n=35, 32 | 35 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | Pre dose (Abn CS), n=33, 31 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -30 minutes (Abn NCS), n=35, 32 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 1 hour (NL), n=33, 30 | 33 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 10 hour (Abn CS), n=32, 31 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 1 hour (Abn NCS), n=33, 30 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -30 minutes (Abn CS), n=35, 32 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 1 hour (Abn CS), n=33, 30 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 12 hour (Abn CS), n=31, 29 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 2 hour (NL), n=31, 28 | 31 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -15 minutes (NL), n=34, 32 | 34 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 2 hour (Abn NCS), n=31, 28 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 10 hour (Abn NCS), n=32, 31 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 2 hour (Abn CS), n=31, 28 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 3 hour (NL), n=31, 27 | 31 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -15 minutes (Abn NCS), n=34, 32 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 24 hour (NL), n=0, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 3 hour (Abn CS), n=31, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -15 minutes (Abn CS), n=34, 32 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 4 hour (NL), n=34, 28 | 34 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 12 hour (NL), n=31, 29 | 31 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 4 hour (Abn CS), n=34, 28 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 6 hour (NL), n=31, 27 | 31 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 24 hour (Abn NCS), n=0, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 6 hour (Abn NCS), n=31, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 6 hour (Abn CS), n=31, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 8 hour (Abn NCS), n=31, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 0 minutes (Abn NCS), n=34, 32 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 10 hour (NL), n=32, 31 | 32 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 0 minutes (NL), n=34, 32 | 34 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 0 minutes (Abn CS), n=34, 32 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 3 hour (Abn NCS), n=31, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 24 hour (Abn CS), n=0, 27 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 4 hour (Abn NCS), n=34, 28 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | Pre dose (NL), n=33, 31 | 33 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 12 hour (Abn NCS), n=31, 29 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | Pre dose (Abn NCS), n=33, 31 | 0 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 8 hour (NL), n=31, 27 | 31 Participants |
| Placebo | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 8 hour (Abn CS), n=31, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 8 hour (NL), n=31, 27 | 27 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 8 hour (Abn CS), n=31, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 10 hour (NL), n=32, 31 | 31 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 10 hour (Abn NCS), n=32, 31 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 10 hour (Abn CS), n=32, 31 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 12 hour (NL), n=31, 29 | 29 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 12 hour (Abn NCS), n=31, 29 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 12 hour (Abn CS), n=31, 29 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 24 hour (NL), n=0, 27 | 27 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 24 hour (Abn NCS), n=0, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 24 hour (Abn CS), n=0, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -30 minutes (Abn NCS), n=35, 32 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -30 minutes (Abn CS), n=35, 32 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -15 minutes (NL), n=34, 32 | 32 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -15 minutes (Abn NCS), n=34, 32 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -15 minutes (Abn CS), n=34, 32 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 0 minutes (NL), n=34, 32 | 32 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 0 minutes (Abn NCS), n=34, 32 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 0 minutes (Abn CS), n=34, 32 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | Pre dose (NL), n=33, 31 | 31 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | Pre dose (Abn NCS), n=33, 31 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | Pre dose (Abn CS), n=33, 31 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 1 hour (NL), n=33, 30 | 30 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 1 hour (Abn NCS), n=33, 30 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 1 hour (Abn CS), n=33, 30 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 2 hour (NL), n=31, 28 | 28 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 2 hour (Abn NCS), n=31, 28 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 3 hour (NL), n=31, 27 | 27 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 3 hour (Abn NCS), n=31, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 3 hour (Abn CS), n=31, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 4 hour (Abn NCS), n=34, 28 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 6 hour (NL), n=31, 27 | 27 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 8 hour (Abn NCS), n=31, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | -30 minutes (NL), n=35, 32 | 32 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 2 hour (Abn CS), n=31, 28 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 4 hour (NL), n=34, 28 | 28 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 4 hour (Abn CS), n=34, 28 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 6 hour (Abn NCS), n=31, 27 | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With 12-lead Holter ECG Findings at the Indicated Time Points | 6 hour (Abn CS), n=31, 27 | 0 Participants |
Secondary
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as 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 or is a congenital anomaly/birth defect, or is an important medical eventsthat jeopardizes the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, new primary cancers, liver events, cardiac dysfunction, pneumonitis, and laboratory abnormalities.
Time frame: From the start of study treatment until follow-up (within approximately 28 days following the last dose of study medication [up to end of Study Week 4])
Population: ATS Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 16 Participants |
| Placebo | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAEs | 0 Participants |
| Lapatinib 2000 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any SAEs | 4 Participants |
| Lapatinib 2000 mg | Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | Any AE | 44 Participants |
Secondary
Number of Participants With the Worst-case Post-Baseline 12-lead Holter ECG Findings With Significant ST, T Wave, and U Wave Abnormalities
Abnormal ECG findings or change in ECG morphological patterns were based on the ECG interpretations provided by the ECG core lab. Three replicate Holter ECGs were collected at 30, 15, and 0 minutes prior to the administration of study treatment on Days 1 (Baseline for placebo) and 3 (Baseline for lapatinib) and pre-dose and 1, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Days 2 and 4. The three readings at each time point were averaged prior to any analysis. Baseline is the pre-dose ECGs (triplicate) taken on Day 1 for placebo and Day 3 for lapatinib. The number of participants with the worst-case post-Baseline 12-lead Holter ECG findings with significant ST, T wave, and U wave abnormalities were analyzed.
Time frame: Baseline (Day1) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 2 for placebo. Baseline (Day 3) and pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, and 24-hours post-dose on Day 4 for lapatinib.
Population: Pharmacodynamic (PD) Population: all participants from the All Treated Subjects Population (ATS) who completed the ECG acquisition via Holter monitoring of at least one time point on Days 1, 2, 3 and 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With the Worst-case Post-Baseline 12-lead Holter ECG Findings With Significant ST, T Wave, and U Wave Abnormalities | 11 Participants |
| Lapatinib 2000 mg | Number of Participants With the Worst-case Post-Baseline 12-lead Holter ECG Findings With Significant ST, T Wave, and U Wave Abnormalities | 14 Participants |