Lorlatinib Renal Impairment Study

AUCinf was calculated by AUClast + (Clast*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration; Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Cmax was observed directly from data.

An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below.

The hematology, chemistry and urinalysis tests were included in the laboratory examination. Hematology evaluation included hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration and erythrocyte mean corpuscular hemoglobin. Chemistry evaluation included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein, lipase and amylase. Urinalysis evaluation included decimal logarithm of reciprocal of hydrogen ion activity [pH], glucose, protein, blood, ketones, microscopy, ketones, nitrite, leukocyte esterase, urobilinogen, urine bilirubin and bacteria. The lab abnormalities were reported in accordance with the sponsor reporting standards.

Vital signs evaluations included supine diastolic blood pressure (DBP), and supine systolic blood pressure (SBP) were measured with the participant's arm supported at the level of the heart and recorded to the nearest mmHg after approximately 5 minutes of rest. Number of participants with vital signs data meeting the categorical summarization criteria is presented. The pre-specified criteria of vital signs data were categorized as follows: SBP (minimum) <90 mmHg, maximum of decrease and increase from baseline for SBP >=30 mmHg; DBP (minimum) <50 mmHg, maximum of decrease and increase from baseline for DBP>=20 mmHg.

ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), and QT interval corrected for heart rate using Fridericia's formula (QTcF interval). The pre-specified criteria of ESG data were categorized as below.

AUClast was calculated by linear/Log trapezoidal method.

Tmax was observed directly from data as time of first occurrence.

t1/2 was calculated by ln(2)/kel.

CL/F was calculated by Dose/AUCinf.

Vz/F was calculated by Dose/(AUCinf*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

CLR was calculated by Ae/AUClast. Ae was cumulative amount of drug recovered unchanged in urine, which was calculated by sum of (urine concentration × sample volume) for each collection interval from 0 to time 120 hours postdose. Sample volume = (urine weight in g/1.020), where 1.020 g/mL is the approximate specific gravity of urine.