Clinical trial NCT03542305: Lorlatinib Renal Impairment Study
Official title: A PHASE 1, SINGLE DOSE OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS OF LORLATINIB IN SUBJECTS WITH IMPAIRED RENAL FUNCTION
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-05-31
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 28 days after last dose of study treatment (approximately 29 days)
measure: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormalities
timeFrame: Screening, Day -1, Day 2 and Day 6
measure: Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria
timeFrame: Baseline up to 28 days after last dose of study treatment (approximately 29 days)
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria
timeFrame: Screening, Day -1, 0 hours (pre-dose), 1 hour, 2 hours, 4 hours, 24 hours and 120 hours postdose.
Other outcomes:
measure: Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: Time for Cmax (Tmax) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: Terminal Elimination Plasma Half-life (t½) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: Apparent Clearance After Oral Dose (CL/F) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: Apparent Volume of Distribution Following Oral Dose (Vz/F) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
measure: Renal Clearance (CLR) of Lorlatinib
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Saint Paul
country: United States
facility: Prism Clinical Research, LLC
state: Minnesota
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Lin S, Gong J, Canas GC, Winkle P, Pelletier K, LaBadie RR, Ginman K, Pithavala YK. A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in Adults with Mild, Moderate, and Severe Renal Impairment. Eur J Drug Metab Pharmacokinet. 2022 Mar;47(2):235-245. doi: 10.1007/s13318-021-00747-4. Epub 2022 Jan 11.