Trial Outcomes & Findings for Hepatic Impairment Study for Lorlatinib in Cancer Patients (NCT NCT03726333)
NCT ID: NCT03726333
Last Updated: 2024-06-21
Results Overview
AUC24 was defined as area under the plasma concentration time profile during 1 dosing interval (24 hours).
TERMINATED
PHASE1
1 participants
Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.
2024-06-21
Participant Flow
A total of 4 participants were screened. Among them, 1 participant was enrolled and treated in Group B (mild impairment), 1 participant was eligible for Group A (normal) but not enrolled as Group A was not open for enrolment at that time, and 2 participants were screen failed.
Participant milestones
| Measure |
Group A1 Normal Hepatic Function
Continued daily administration of lorlatinib 100 mg in patients with normal hepatic function until disease progression, patient refusal, or unacceptable toxicity occurrence
|
Group A2 Normal Hepatic Function
Continued daily administration of lorlatinib in patients with normal hepatic function at the dose level same as Group C for the first 22 days and 100 mg once a day (QD) afterwards.
|
Group B Mild Hepatic Impairment
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
Group C Moderate Hepatic Impairment
Continued daily administration of lorlatinib in patients with moderate hepatic impairment at 50 mg QD initially and may be adjusted based on PK and safety results from the initial several patients.
|
Group D Severe Hepatic Impairment
Continued daily administration of lorlatinib in patients with severe hepatic impairment at the dose level determined based on preliminary PK and safety results from first several patients in Group C.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Group A1 Normal Hepatic Function
Continued daily administration of lorlatinib 100 mg in patients with normal hepatic function until disease progression, patient refusal, or unacceptable toxicity occurrence
|
Group A2 Normal Hepatic Function
Continued daily administration of lorlatinib in patients with normal hepatic function at the dose level same as Group C for the first 22 days and 100 mg once a day (QD) afterwards.
|
Group B Mild Hepatic Impairment
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
Group C Moderate Hepatic Impairment
Continued daily administration of lorlatinib in patients with moderate hepatic impairment at 50 mg QD initially and may be adjusted based on PK and safety results from the initial several patients.
|
Group D Severe Hepatic Impairment
Continued daily administration of lorlatinib in patients with severe hepatic impairment at the dose level determined based on preliminary PK and safety results from first several patients in Group C.
|
|---|---|---|---|---|---|
|
Overall Study
Progressive Disease
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Hepatic Impairment Study for Lorlatinib in Cancer Patients
Baseline characteristics by cohort
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Age, Categorical
<=18 years
|
NA Participants
n=39 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
NA Participants
n=39 Participants
|
|
Age, Categorical
>=65 years
|
NA Participants
n=39 Participants
|
|
Sex: Female, Male
Female
|
NA Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
NA Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
NA Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
NA Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
NA Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
NA Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
NA Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
NA Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
NA Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
NA Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
NA Participants
n=39 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
NA Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
AUC24 was defined as area under the plasma concentration time profile during 1 dosing interval (24 hours).
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Area Under Plasma Lorlatinib Concentration-Time Curve From Time 0 to Dosing Interval of 24 Hours (AUC24) at Steady State On Cycle 2 Day 1
|
NA nanogram*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant
|
PRIMARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Cmax was defined as maximum plasma concentration and was observed directly from data.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Observed Maximal Plasma Concentration (Cmax) at Steady State on Cycle 2 Day 1
|
NA nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.
An Adverse event (AE) was any untoward medical occurrence in a participant. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or that was considered to be an important medical event. AEs were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. The grades were defined as follows: Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. The focus of AE summaries was on treatment-emergent AE (TEAE). An AE was considered TEAE if the event occurred during the on-treatment period.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
All-causality TEAEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
Treatment-related TEAEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
All-causality serious AEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
Treatment-related serious AEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
All-causalities AEs ≥Grade 3
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
Treatment-related AEs ≥Grade 3
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
All-causalities Grade 1 AEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
Treatment-related Grade 1 AEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
All-causalities Grade 2 AEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
|
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
Treatment-related Grade 2 AEs
|
NA Participants
Data cannot be reported because doing so would risk re-identification of the participant.
|
SECONDARY outcome
Timeframe: Baseline up to approximately 1 yearPopulation: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.
ORR was defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 relative to the response-evaluable population.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Objective Response Rate (ORR)
|
0 Percentage of participants
Interval 0.0 to 97.5
|
SECONDARY outcome
Timeframe: Baseline up to approximately 1 yearPopulation: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.
DR was measured from the date that an objective tumor response (CR or PR) was first documented (whichever occurred first) to date of objective tumor progression or death due to any cause, whichever occurred first.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Duration of Response (DR)
|
NA Months
The participant had an overall objective tumor assessment of progressive disease. As no patient responded DR is Not Applicable.
|
SECONDARY outcome
Timeframe: Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast)
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Lorlatinib Area Under Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) After Single Dose on Cycle 1 Day 1
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Tlast was defined as the time of the last quantifiable concentration.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
The Time of The Last Quantifiable Concentration (Tlast) of Lorlatinib After Single Dose on Cycle 1 Day 1
|
NA hour
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Tmax was defined as time for Cmax.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1
|
NA hour
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Cmin was defined as minimum plasma concentration and was observed directly from data.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Observed Minimal Plasma Concentration (Cmin) at Steady State On Cycle 2 Day 1
|
NA ng/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib AUClast at Steady State On Cycle 2 Day 1
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Tlast was defined as the time of the last quantifiable concentration.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1
|
NA hour
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as Dose/AUC24 at steady-state.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Apparent Clearance (CL/F) at Steady State On Cycle 2 Day 1
|
NA Liter per hour (L/hr)
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
AUC24 was defined as area under the plasma concentration time profile during one dosing interval (24 hours).
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Metabolite AUC24 at Steady State
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Metabolite AUClast After Single Dose
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Metabolite AUClast at Steady State
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Cmax was defined as maximum plasma concentration and was observed directly from data.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Metabolite Cmax After Single Dose
|
NA ng/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Cmax was defined as maximum plasma concentration and was observed directly from data.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Metabolite Cmax at Steady State
|
NA ng/mL
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Tlast was defined as the time of the last quantifiable concentration.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Metabolite Tlast After Single Dose
|
NA hour
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
Tlast was defined as the time of the last quantifiable concentration.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Plasma Lorlatinib Metabolite Tlast at Steady State
|
NA hour
No PK parameter estimation was performed for the 1 treated participant
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
MRAUC24 was defined as metabolite ratio of lorlatinib metabolite for AUC24.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Metabolite Ratio of Lorlatinib Metabolite for AUC24 (MRAUC24) at Steady State on Cycle 2 Day 1
|
NA Ratio
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 2 Day 1
|
NA Ratio
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
MRCmax was defined as metabolite ratio of lorlatinib metabolite for AUClast.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Metabolite Ratio of Lorlatinib Metabolite for Cmax (MRCmax) at Steady State on Cycle 2 Day 1
|
NA Ratio
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
SECONDARY outcome
Timeframe: Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose.Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest.
MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.
Outcome measures
| Measure |
Group B Mild Hepatic Impairment
n=1 Participants
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 1 Day 1
|
NA Ratio
Geometric Coefficient of Variation NA
No PK parameter estimation was performed for the 1 treated participant.
|
Adverse Events
Group B Mild Hepatic Impairment
Serious adverse events
| Measure |
Group B Mild Hepatic Impairment
n=1 participants at risk
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
Nervous system disorders
Nervous system disorders
|
100.0%
1/1 • From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.
AE information were reported by using the System Organ Class instead of preferred term to avoid the risk of re-identification of the participant.
|
|
Psychiatric disorders
Psychiatric disorders
|
100.0%
1/1 • From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.
AE information were reported by using the System Organ Class instead of preferred term to avoid the risk of re-identification of the participant.
|
Other adverse events
| Measure |
Group B Mild Hepatic Impairment
n=1 participants at risk
Continued daily administration of lorlatinib in patients with mild hepatic impairment. The participant received lorlatinib 100 mg QD in Cycle 1 and lorlatinib 75 mg QD in Cycle 2.
|
|---|---|
|
General disorders
General disorders
|
100.0%
1/1 • From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.
AE information were reported by using the System Organ Class instead of preferred term to avoid the risk of re-identification of the participant.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
100.0%
1/1 • From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.
AE information were reported by using the System Organ Class instead of preferred term to avoid the risk of re-identification of the participant.
|
|
Nervous system disorders
Nervous system disorders
|
100.0%
1/1 • From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.
AE information were reported by using the System Organ Class instead of preferred term to avoid the risk of re-identification of the participant.
|
|
Psychiatric disorders
Psychiatric disorders
|
100.0%
1/1 • From Screening (within 28 days prior to Cycle 1 Day 1) through and including at least 28 days after after the last lorlatinib dose. The duration is approximately 42 days.
AE information were reported by using the System Organ Class instead of preferred term to avoid the risk of re-identification of the participant.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER