A Study to Learn About the Study Medicine (Called Lorlatinib) in People With Liver Dysfunction

NCT05224609 | Completed Phase 1 FDA Drug

• 1 other identifier: B7461040
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called Lorlatinib) in health participants. This study is seeking participants who:

• Must be male or female of 18 to 75 years of age, inclusive at the time of the study.
• Are willing and able to comply with all scheduled visits, treatment plan, and other study procedures.
• Have a BMI (body mass index) of 17.5 to 40 kg/m2; and a total body weight \>50 kg (110 lb).
• Are capable of giving signed informed consent document. All participants in this study will receive Lorlatinib. Participants will be placed into 1 of 3 cohorts based on their hepatic (liver) function. Participants will take Lorlatinib once by mouth. We will examine the experiences of people receiving the study medicine. This will help us determine if the study medicine is safe and effective. Participants will take part in this study for up to 35 days.

Conditions

Moderate Hepatic Impairment; Severe Hepatic Impairment; Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Single dose Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (inf)] of lorlatinib

  PK parameter of lorlatinib to be calculated from the plasma concentration time data.

  0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post-dose

• Single dose Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (last)] of lorlatinib

  PK parameter of lorlatinib to be calculated from the plasma concentration time data.

  0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post-dose

• Single dose Maximum Observed Plasma Concentration (Cmax) of lorlatinib

  Maximum lorlatinib plasma concentration observed during study.

  0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post-dose

Secondary Outcomes (6)

• Number of participants experienced treatment emergent adverse event assessed by investigator

  Baseline up to Day 35

• Number of participants experienced treatment related adverse event assessed by investigator

  Baseline up to Day 35

• Number of participants experienced serious adverse event assessed by investigator

  Baseline up to Day 35

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  Baseline up to Day 35

• Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities

  Baseline up to Day 8

Study Arms (3)

Cohort 1

EXPERIMENTAL

Moderate hepatic impairment group

Drug: Lorlatinib

Cohort 2

EXPERIMENTAL

Severe hepatic impairment group

Drug: Lorlatinib

Cohort 3

EXPERIMENTAL

Normal hepatic function

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

Single 100mg oral dose anti-cancer agent

Also known as: Lorbrena, PF-06463922

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• All Participants -
• Participants must be male or female of 18 to 75 years of age, inclusive, at the time of signing the ICD.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• BMI of 17.5 to 40 kg/m2; and a total body weight \>50 kg (110 lb).
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
• Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, complete physical examination, including BP and pulse rate measurement, 12-lead ECG or clinical laboratory tests. Particularly, should confirm no known or suspected hepatic impairment based on liver function tests (eg, ALT, AST, ALP, and bilirubin), albumin and prothrombin time.
• Participants must fit the demographic-matching criteria, including: Body weight +- 15 kg of the median of the combined moderate and severe hepatic impairment cohorts (Cohorts 1 and 2), as provided by the sponsor.
• Age +- 10 years of the median of the combined moderate and severe hepatic impairment cohorts (Cohorts 1 and 2), as provided by the sponsor.
• Comparable male/female ratio to moderate and severe hepatic impairment cohorts (Cohorts 1 and 2).
• Meet the criteria for Class B (moderate hepatic impairment) of the modified Child-Pugh classification.
• A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, computerized tomography scan, or MRI.
• Stable hepatic impairment, defined as no clinically significant known change in disease status within the last 30 days, as documented by the participant's recent medical history (eg, no worsening clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin time by more than 50%).
• Stable drug regimen is defined as not starting a new drug or changing dosage within 7 days or 5 half-lives (whichever is longer) prior to the dosing of lorlatinib.
• History of alcohol abuse is permissible providing that the results of alcohol test are negative at Screening or on Day -1, and the participant is willing and able to abide by the lifestyle guidelines.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• All Participants -
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
• History of or current positive results for HIV infection.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg. Contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Participants with an eGFR of ≤ 60 mL/min/1.73 m2 based on the 2021 CKD-EPI equation, with a single repeat permitted to assess eligibility, if needed.
• Concurrent use of any of the following prohibited concomitant medication(s) within 12 days prior to the first dose of lorlatinib:
• Known strong CYP3A inhibitors (eg, boceprevir, cobicistat, clarithromycin, conivaptan, diltiazem, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, tipranavir, troleandomycin, voriconazole, grapefruit juice or grapefruit/grapefruit-related citrus fruits \[eg Seville oranges, pomelos\]). The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
• Known strong CYP3A inducers (eg, carbamazepine, enzalutamide, mitotane, phenytoin, rifabutin, rifampin, St. John's Wort).
• Known P-gp substrates with a narrow therapeutic index (eg, digoxin).
• Concurrent use of CYP3A substrates with narrow therapeutic indices (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl including transdermal patch, pimozide, quinidine, sirolimus, tacrolimus) within 12 days prior to the first dose of lorlatinib.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• Known hypersensitivity to lorlatinib or its excipients.
• A positive urine drug test. Participants with moderate or severe hepatic impairment (Cohorts 1 and 2) will be eligible to participate if their urine drug test is positive with a drug for a prescribed condition that is not expected to interfere with the PK of lorlatinib.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

Orange County Research Center

Tustin, California, 92780, United States

Location

Genesis Clinical Research, LLC

Tampa, Florida, 33603, United States

Location

Prism Research LLC dba Nucleus Network

Saint Paul, Minnesota, 55114, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

lorlatinib

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 4, 2022
• Study Start: April 28, 2022
• Primary Completion: August 13, 2024
• Study Completion: August 13, 2024
• Last Updated: August 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)