What side effects are associated with this type of intervention?

Common side effects of treatments similar to Lorlatinib, such as crizotinib and iruplinalkib, include mild visual disturbances, nausea, vomiting, elevated ALT/AST levels, fatigue, gastrointestinal issues, and hypertension. A significant portion of patients may experience grade 3 or higher adverse events.

What prior FDA approvals exist?

Lorlatinib is an ALK and ROS1 inhibitor used in the treatment of non-small cell lung cancer (NSCLC). Similar drugs that have received FDA approval include Crizotinib, Ceritinib, Alectinib, Brigatinib, and Entrectinib. These drugs target genetic mutations in ALK and ROS1, providing effective treatment options for patients with specific types of NSCLC. While these approvals primarily focus on cancer treatment, studies involving healthy subjects are typically conducted to assess safety and pharmacokinetics before broader clinical use.

What other types of research exist?

Promising novel alternatives to Lorlatinib for ALK and ROS1 inhibition include Brigatinib and Alectinib. Both have shown efficacy in treating ALK-positive NSCLC and are considered effective options for patients who may not respond to or tolerate Lorlatinib.

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Tyrosine Kinase Inhibitor

Lorlatinib for Liver Dysfunction

Phase 1

Waitlist Available

Research Sponsored by Pfizer

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

BMI of 17.5 to 40 kg/m2; and a total body weight >50 kg (110 lb)

Participants must be male or female of nonchildbearing potential of 18 to 75 years of age, inclusive, at the time of signing the ICD

Must not have

Participants must not have any condition possibly affecting drug absorption, history of or current positive results for HIV infection, or other medical or psychiatric conditions that may increase the risk of study participation

Participants with an eGFR of ≤ 60 mL/min/1.73 m2 are excluded

Timeline

Screening 3 weeks

Treatment Varies

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

Awards & highlights

No Placebo-Only Group

Summary

This trial tests Lorlatinib, a pill, in adults with different liver functions. Researchers will see how the medicine moves through the body and check for any side effects. Lorlatinib is approved for the treatment of a specific type of lung cancer.

Who is the study for?

This trial is for adults aged 18-75 with liver dysfunction or healthy individuals matching certain criteria. Participants must have a BMI of 17.5 to 40 kg/m2 and weigh over 50 kg (110 lb). They should be able to follow the study plan and give informed consent. People with HIV, recent drug use, significant blood donations, or sensitivity to heparin are excluded.

What is being tested?

The trial tests Lorlatinib's safety and effects in people with varying levels of liver function. Participants will take one dose orally and are grouped into cohorts based on their liver health: normal function, moderate impairment, or severe impairment.

What are the potential side effects?

While specific side effects for Lorlatinib in this context aren't listed, common ones may include fatigue, vision issues, cognitive effects like confusion or mood changes, high cholesterol levels, and possible swelling due to fluid retention.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My BMI is between 17.5 and 40, and I weigh more than 50 kg (110 lb).

Select...

I am between 18 and 75 years old and cannot become pregnant or get someone pregnant.

Select...

My liver function is moderately impaired but stable.

Select...

My liver function is severely impaired but stable.

Select...

I am healthy with normal liver function and no significant medical issues.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I don't have conditions that could affect medication absorption, HIV, or risky health issues.

Select...

My kidney function, measured by eGFR, is above 60 mL/min/1.73 m2.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

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

Screening ~ 3 weeks

Treatment ~ Varies

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

This trial's timeline: 3 weeks for screening, Varies for treatment, and 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post-dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

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

Single dose Maximum Observed Plasma Concentration (Cmax) of lorlatinib

Secondary study objectives

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

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

Number of participants experienced serious adverse event assessed by investigator

+3 more

Side effects data

From 2020 Phase 1 trial • 29 Patients • NCT03542305

13%

Diarrhoea

13%

Ecchymosis

13%

Dizziness

13%

Headache

13%

Upper respiratory tract infection

13%

Skin abrasion

100%

80%

60%

40%

20%

Study treatment Arm

Moderate Impairment

Severe Impairment

Mild Impairment

Normal Function

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Cohort 3Experimental Treatment1 Intervention

Normal hepatic function

Group II: Cohort 2Experimental Treatment1 Intervention

Severe hepatic impairment group

Group III: Cohort 1Experimental Treatment1 Intervention

Moderate hepatic impairment group

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lorlatinib

2018

Completed Phase 4

~530

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

ALK and ROS1 inhibitors, such as Lorlatinib, work by targeting and blocking the activity of the ALK and ROS1 proteins, which are involved in the growth and survival of cancer cells. This mechanism is crucial for healthy subjects in clinical trials to ensure that the drug can effectively target cancer cells while minimizing adverse effects on normal cells. Studying these effects in healthy subjects helps establish the safety profile and optimal dosing of the drug before it is used in patients with cancer.

Safety profile of new anticancer drugs.Potential of interferon-alpha in solid tumours: part 2.