Advanced Cancers
Conditions
Keywords
hepatic impairment, lorlatinib, cancer, pharmacokinetic, Lung cancer
Brief summary
This is a phase 1 study in advanced cancer patients with varied hepatic functions to evaluate the potential effect of hepatic impairment on pharmacokinetics and safety of lorlatinib and provide dose recommendation for patients with hepatic impairment if possible.
Detailed description
This will be a Phase 1, open label, multi center, multiple dose, non randomized, Phase 1 clinical trial of lorlatinib in advanced cancer patients with varying degrees of hepatic impairment and necessary age , weight , and gender matched prospect normal hepatic function patients. This study is intended to evaluate the potential effect of hepatic impairments on the PK and safety of lorlatinib after daily administration of lorlatinib and to provide dosing recommendation for patients with varied degree of hepatic impairment if possible. Patients in the study will be assigned to different groups (A1, normal liver function, control for group B; A2, normal liver function, control for group C; B, mild hepatic impairment; C, moderate hepatic impairment; D, severe hepatic impairment) according to their liver function. The enrollment of approximately 76 advanced cancer patients is anticipated in this study in order to have 8 PK-evaluable patients in each of Groups A1, A2, B and C, and 6 PK-evaluable patients in Group D for final statistical analysis. Evaluable patients are those who complete the planned PK sample collection on Cycle 2 Day 1 and have no lorlatinib dose modification until completion of Cycle 2 Day 1 PK evaluation. Patients who are not evaluable for PK will be replaced. Each patient will be treated with repeated oral once daily doses of lorlatinib in 21-day cycles until disease progression, patient refusal, or unacceptable toxicity occurs. The dose schedule may be modified as necessary for individual patients according to tolerability.
Interventions
DRUGlorlatinib
continued daily administration of 100 mg lorlatinib
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients in the study will be assigned to different groups according to their liver function. Patients in each group will receive specific lorlatinib dose. Plasma samples for pharmacokinetic analysis will be collected in all patients. Safety and efficacy will also be followed in all patients until at least 28 days after the last study treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective; * Biliary obstruction with a biliary drain or stent; * Neurologically stable gliomas and brain metastases; * ECOG performance status of 0, 1, or 2; * adequate bone marrow function; * adequate pancreatic function; * adequate renal function; * female patients with negative pregnancy test
Exclusion criteria
* untreated esophageal varices; uncontrolled ascites; * episodes of hepatic encephalopathy within the last 4 weeks; * spinal cord compression; major surgery within 4 weeks prior to enrollment; * radiation therapy within 2 weeks prior to enrollment; * last anti-cancer treatment within 2 weeks prior to screening; * previous high-dose chemotherapy requiring stem cell rescue; * prior to irradiation to \>25% of the bone marrow; * gastrointestinal abnormalities; * known prior or suspected hypersensitivity to lorlatinib or lorlatinib tablet; * clinically significant bacterial, fungal or viral infections for non-liver cancer patients; * clinically significant cardiovascular disease; * uncontrolled hypertension; acute pancreatitis with predisposing characteristics; * history of grade 3 or 4 interstitial fibrosis or interstitial lung disease; * active hemoelysis or evidence of biliary sepsis; * prior major gastrointestinal surgery; * concurrent use of known strong CYP3A inhibitors, inducers and P-gp substrates with a narrow therapeutic index; * concurrent use of CYP3A substrates with narrow therapeutic indices; * prior treatment with lorlatinib; active bleeding disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | AUC24 was defined as area under the plasma concentration time profile during 1 dosing interval (24 hours). |
| Observed Maximal Plasma Concentration (Cmax) at Steady State on Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Cmax was defined as maximum plasma concentration and was observed directly from data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DR) | Baseline up to approximately 1 year | 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. |
| 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 | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | AUClast was defined as area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast) |
| The Time of The Last Quantifiable Concentration (Tlast) of Lorlatinib After Single Dose on Cycle 1 Day 1 | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Tlast was defined as the time of the last quantifiable concentration. |
| The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1 | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Tmax was defined as time for Cmax. |
| Observed Minimal Plasma Concentration (Cmin) at Steady State On Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Cmin was defined as minimum plasma concentration and was observed directly from data. |
| Plasma Lorlatinib AUClast at Steady State On Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast. |
| Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Tlast was defined as the time of the last quantifiable concentration. |
| Apparent Clearance (CL/F) at Steady State On Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | 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. |
| Plasma Lorlatinib Metabolite AUC24 at Steady State | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | AUC24 was defined as area under the plasma concentration time profile during one dosing interval (24 hours). |
| Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | 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. | 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. |
| Plasma Lorlatinib Metabolite AUClast at Steady State | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast. |
| Plasma Lorlatinib Metabolite Cmax After Single Dose | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Cmax was defined as maximum plasma concentration and was observed directly from data. |
| Plasma Lorlatinib Metabolite Cmax at Steady State | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Cmax was defined as maximum plasma concentration and was observed directly from data. |
| Plasma Lorlatinib Metabolite Tlast After Single Dose | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Tlast was defined as the time of the last quantifiable concentration. |
| Plasma Lorlatinib Metabolite Tlast at Steady State | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | Tlast was defined as the time of the last quantifiable concentration. |
| Metabolite Ratio of Lorlatinib Metabolite for AUC24 (MRAUC24) at Steady State on Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | MRAUC24 was defined as metabolite ratio of lorlatinib metabolite for AUC24. |
| Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast. |
| Metabolite Ratio of Lorlatinib Metabolite for Cmax (MRCmax) at Steady State on Cycle 2 Day 1 | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | MRCmax was defined as metabolite ratio of lorlatinib metabolite for AUClast. |
| Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 1 Day 1 | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast. |
| Plasma Lorlatinib Metabolite AUClast After Single Dose | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. | AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast. |
| Objective Response Rate (ORR) | Baseline up to approximately 1 year | 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Progressive Disease | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Group B Mild Hepatic Impairment |
|---|---|
| Age, Categorical <=18 years | NA Participants |
| Age, Categorical >=65 years | NA Participants |
| Age, Categorical Between 18 and 65 years | NA Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | NA Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | NA Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | NA Participants |
| Race (NIH/OMB) American Indian or Alaska Native | NA Participants |
| Race (NIH/OMB) Asian | NA Participants |
| Race (NIH/OMB) Black or African American | NA Participants |
| Race (NIH/OMB) More than one race | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | NA Participants |
| Race (NIH/OMB) Unknown or Not Reported | NA Participants |
| Race (NIH/OMB) White | NA Participants |
| Sex: Female, Male Female | NA Participants |
| Sex: Female, Male Male | NA Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
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
AUC24 was defined as area under the plasma concentration time profile during 1 dosing interval (24 hours).
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | 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) |
Primary
Observed Maximal Plasma Concentration (Cmax) at Steady State on Cycle 2 Day 1
Cmax was defined as maximum plasma concentration and was observed directly from data.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Observed Maximal Plasma Concentration (Cmax) at Steady State on Cycle 2 Day 1 | NA nanogram per milliliter (ng/mL) |
Secondary
Apparent Clearance (CL/F) at Steady State On Cycle 2 Day 1
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Apparent Clearance (CL/F) at Steady State On Cycle 2 Day 1 | NA Liter per hour (L/hr) |
Secondary
Duration of Response (DR)
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.
Time frame: Baseline up to approximately 1 year
Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Duration of Response (DR) | NA Months |
Secondary
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
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | 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 |
Secondary
Metabolite Ratio of Lorlatinib Metabolite for AUC24 (MRAUC24) at Steady State on Cycle 2 Day 1
MRAUC24 was defined as metabolite ratio of lorlatinib metabolite for AUC24.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Metabolite Ratio of Lorlatinib Metabolite for AUC24 (MRAUC24) at Steady State on Cycle 2 Day 1 | NA Ratio |
Secondary
Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 1 Day 1
MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 1 Day 1 | NA Ratio |
Secondary
Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 2 Day 1
MRAUClast was defined as metabolite ratio of lorlatinib metabolite for AUClast.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Metabolite Ratio of Lorlatinib Metabolite for AUClast (MRAUClast) at Steady State on Cycle 2 Day 1 | NA Ratio |
Secondary
Metabolite Ratio of Lorlatinib Metabolite for Cmax (MRCmax) at Steady State on Cycle 2 Day 1
MRCmax was defined as metabolite ratio of lorlatinib metabolite for AUClast.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Metabolite Ratio of Lorlatinib Metabolite for Cmax (MRCmax) at Steady State on Cycle 2 Day 1 | NA Ratio |
Secondary
Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | All-causality TEAEs | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | Treatment-related TEAEs | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | All-causality serious AEs | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | Treatment-related serious AEs | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | All-causalities AEs ≥Grade 3 | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | Treatment-related AEs ≥Grade 3 | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | All-causalities Grade 1 AEs | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | Treatment-related Grade 1 AEs | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | All-causalities Grade 2 AEs | NA Participants |
| Group B Mild Hepatic Impairment | Number Of Patients Experienced Treatment Emergent Adverse Event Assessed by Investigator | Treatment-related Grade 2 AEs | NA Participants |
Secondary
Objective Response Rate (ORR)
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.
Time frame: Baseline up to approximately 1 year
Population: The analysis population included all enrolled participants who received at least 1 dose of lorlatinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group B Mild Hepatic Impairment | Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Observed Minimal Plasma Concentration (Cmin) at Steady State On Cycle 2 Day 1
Cmin was defined as minimum plasma concentration and was observed directly from data.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Observed Minimal Plasma Concentration (Cmin) at Steady State On Cycle 2 Day 1 | NA ng/mL |
Secondary
Plasma Lorlatinib AUClast at Steady State On Cycle 2 Day 1
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib AUClast at Steady State On Cycle 2 Day 1 | NA ng*hr/mL |
Secondary
Plasma Lorlatinib Metabolite AUC24 at Steady State
AUC24 was defined as area under the plasma concentration time profile during one dosing interval (24 hours).
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Metabolite AUC24 at Steady State | NA ng*hr/mL |
Secondary
Plasma Lorlatinib Metabolite AUClast After Single Dose
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Metabolite AUClast After Single Dose | NA ng*hr/mL |
Secondary
Plasma Lorlatinib Metabolite AUClast at Steady State
AUClast was defined as area under the plasma concentration time profile from time 0 to the time of Clast.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Metabolite AUClast at Steady State | NA ng*hr/mL |
Secondary
Plasma Lorlatinib Metabolite Cmax After Single Dose
Cmax was defined as maximum plasma concentration and was observed directly from data.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Metabolite Cmax After Single Dose | NA ng/mL |
Secondary
Plasma Lorlatinib Metabolite Cmax at Steady State
Cmax was defined as maximum plasma concentration and was observed directly from data.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Metabolite Cmax at Steady State | NA ng/mL |
Secondary
Plasma Lorlatinib Metabolite Tlast After Single Dose
Tlast was defined as the time of the last quantifiable concentration.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Metabolite Tlast After Single Dose | NA hour |
Secondary
Plasma Lorlatinib Metabolite Tlast at Steady State
Tlast was defined as the time of the last quantifiable concentration.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Metabolite Tlast at Steady State | NA hour |
Secondary
Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1
Tlast was defined as the time of the last quantifiable concentration.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1 | NA hour |
Secondary
The Time of The Last Quantifiable Concentration (Tlast) of Lorlatinib After Single Dose on Cycle 1 Day 1
Tlast was defined as the time of the last quantifiable concentration.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | The Time of The Last Quantifiable Concentration (Tlast) of Lorlatinib After Single Dose on Cycle 1 Day 1 | NA hour |
Secondary
The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1
Tmax was defined as time for Cmax.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group B Mild Hepatic Impairment | The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1 | NA hour |