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| ID | Type | Description | Link |
|---|---|---|---|
| lorlatinib HEPATIC IMPAIRMENT | Other Identifier | Alias Study Number | |
| HEPATIC IMPAIRMENT | Other Identifier | Alias Study Number |
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The study stopped due to lack of enrollment
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A1 Normal hepatic function | Active Comparator | continued daily administration of lorlatinib in patients with normal hepatic function |
|
| Group A2 Normal hepatic function | Active Comparator | continued daily administration of lorlatinib in patients with normal hepatic function |
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| Group B mild hepatic impairment | Experimental | continued daily administration of lorlatinib in patients with mild hepatic impairment |
|
| Group C moderate hepatic impairment | Experimental | continued daily administration of lorlatinib in patients with moderate hepatic impairment |
|
| Group D severe hepatic impairment | Experimental | continued daily administration of lorlatinib in patients with severe hepatic impairment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lorlatinib | Drug | continued daily administration of 100 mg lorlatinib |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Denver CTO (CTRC) | Aurora | Colorado | 80045 | United States | ||
| University of Colorado Hospital, Anschutz Cancer Pavilion (ACP) |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nervous system disorders | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| General disorders | General disorders | MedDRA v24.1 | Non-systematic Assessment |
The study was terminated due to difficulties with enrolling eligible patients. Only 1 participant was enrolled in this study. Outcome measures and AE data were not reported as planned in the protocol because doing so would risk re-dentification of the individual participant.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials_gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 14, 2019 | Jun 6, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 24, 2018 | Jun 6, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008175 | Lung Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C000590786 | lorlatinib |
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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.
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| lorlatinib |
| Drug |
continued daily administration of lorlatinib at the dose level same as Group C for the first 22 days and 100 mg QD afterwards |
|
| lorlatinib | Drug | continued daily administration of 100 mg QD lorlatinib |
|
| lorlatinib | Drug | continued daily administration of lorlatinib at 50 mg QD initially and may be adjusted based on PK and safety results from the initial several patients |
|
| lorlatinib | Drug | continued daily administration of lorlatinib at the dose level determined based on preliminary PK and safety results from first several patients in Group C |
|
| 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. |
| 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. | Baseline up to approximately 1 year |
| 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. | Baseline up to approximately 1 year |
| 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) | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1 | Tmax was defined as time for Cmax. | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1 | Tlast was defined as the time of the last quantifiable concentration. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Plasma Lorlatinib Metabolite AUC24 at Steady State | AUC24 was defined as area under the plasma concentration time profile during one dosing interval (24 hours). | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Plasma Lorlatinib Metabolite Cmax After Single Dose | Cmax was defined as maximum plasma concentration and was observed directly from data. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Plasma Lorlatinib Metabolite Cmax at Steady State | Cmax was defined as maximum plasma concentration and was observed directly from data. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Plasma Lorlatinib Metabolite Tlast After Single Dose | Tlast was defined as the time of the last quantifiable concentration. | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Plasma Lorlatinib Metabolite Tlast at Steady State | Tlast was defined as the time of the last quantifiable concentration. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| 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. | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
| Aurora |
| Colorado |
| 80045 |
| United States |
| University of Colorado Hospital, Anschutz Inpatient Pavilion (AIP) | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital, Anschutz Outpatient Pavilion (AOP) | Aurora | Colorado | 80045 | United States |
| Emory University Hospital | Atlanta | Georgia | 30322 | United States |
| Investigational Drug Service | Atlanta | Georgia | 30322 | United States |
| The Emory Clinic | Atlanta | Georgia | 30322 | United States |
| Winship Cancer Institute, Emory University | Atlanta | Georgia | 30322 | United States |
| Mays Cancer Center | San Antonio | Texas | 78229 | United States |
| University Health System | San Antonio | Texas | 78229 | United States |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
|
|
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| 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. | The analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Count of Participants | Participants | 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. |
|
|
|
| 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. | The analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Number | 95% Confidence Interval | Percentage of participants | Baseline up to approximately 1 year |
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| 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. | The analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Median | 95% Confidence Interval | Months | Baseline up to approximately 1 year |
|
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| 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) | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
|
|
|
| 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. | 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. | Posted | Median | Full Range | hour | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
|
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| Secondary | The Time to Cmax (Tmax) of Lorlatinib After Single Dose on Cycle 1 Day 1 | Tmax was defined as time for Cmax. | 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. | Posted | Median | Full Range | hour | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
|
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| Secondary | Plasma Lorlatinib Tlast at Steady State On Cycle 2 Day 1 | Tlast was defined as the time of the last quantifiable concentration. | 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. | Posted | Median | Full Range | hour | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour (L/hr) | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| Secondary | Plasma Lorlatinib Metabolite Cmax After Single Dose | Cmax was defined as maximum plasma concentration and was observed directly from data. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| Secondary | Plasma Lorlatinib Metabolite Cmax at Steady State | Cmax was defined as maximum plasma concentration and was observed directly from data. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| Secondary | Plasma Lorlatinib Metabolite Tlast After Single Dose | Tlast was defined as the time of the last quantifiable concentration. | 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. | Posted | Median | Full Range | hour | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| Secondary | Plasma Lorlatinib Metabolite Tlast at Steady State | Tlast was defined as the time of the last quantifiable concentration. | 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. | Posted | Median | Full Range | hour | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Cycle 2 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Cycle 1 day 1 at times 0 (predose), 0.5, 1, 2, 4, 6, 10, and 24 hours post lorlatinib dose. |
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| 0 |
| 1 |
| 1 |
| 1 |
| 1 |
| 1 |
| Psychiatric disorders | Psychiatric disorders | MedDRA v24.1 | Non-systematic Assessment |
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| Metabolism and nutrition disorders | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
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| Nervous system disorders | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
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| Psychiatric disorders | Psychiatric disorders | MedDRA v24.1 | Non-systematic Assessment |
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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.
| D012140 |
| Respiratory Tract Diseases |
| All-causality serious AEs |
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| Treatment-related serious AEs |
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| All-causalities AEs ≥Grade 3 |
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| Treatment-related AEs ≥Grade 3 |
|
| All-causalities Grade 1 AEs |
|
| Treatment-related Grade 1 AEs |
|
| All-causalities Grade 2 AEs |
|
| Treatment-related Grade 2 AEs |
|