Lorlatinib Renal Impairment Study

Pfizer29 enrolled

Overview

This is a Phase 1, open-label, multi-center, single treatment study in subjects with normal renal function and varying degrees of renal impairment.

This is a Phase 1, open-label, multi-center, single treatment study in subjects with normal renal function and varying degrees of renal impairment. Each subject will receive a single oral dose of lorlatinib administered in the fasted state. Subjects with mild, moderate, and severe renal impairment will be enrolled and normal healthy subjects will be enrolled as matched controls.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Renal Impairment

Interventions

LorlatinibDRUG

Lorlatinib single oral dose

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Female subjects of non-childbearing potential * Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb) * Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study * Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. * Demonstrate stable renal function Exclusion Criteria: * Renal allograft recipients * Any condition possibly affecting drug absorption (eg, gastrectomy) * A positive urine drug test * History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (1 drink = 5 ounces \[150 mL\] of wine or 12 ounces \[360 mL\] of beer or 1.5 ounces \[45 mL\] of hard liquor) within 6 months before screening. * Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer). * Screening supine triplicate 12 lead ECG demonstrating a corrected QT (QTc) interval \>450 msec or a QRS interval \>120 msec * Second-degree or third-degree AV block (unless paced) or baseline PR interval \>180 msec at any time prior to dosing of study treatment. * Abnormalities in clinical laboratory tests at screening * Pregnant or breastfeeding female subjects * History of HIV, Hepatitis B, Hepatitis C, HIT, sensitivity to heparin * Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation

Locations (2)

Anaheim Clinical Trials, LLC

Anaheim, California, United States

Prism Clinical Research, LLC

Saint Paul, Minnesota, United States

Outcomes

Primary Outcomes

Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib

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.

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose

Maximum Observed Plasma Concentration (Cmax) of Lorlatinib

Cmax was observed directly from data.

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose

Secondary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

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.

Time frame: Baseline up to 28 days after last dose of study treatment (approximately 29 days)

Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormalities

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.