Back to resultsLorlatinib Renal Impairment Study
Primary Purpose
Renal Impairment
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lorlatinib
Sponsored by
About this trial
This is an interventional other trial for Renal Impairment
Eligibility Criteria
Inclusion Criteria:
- Female subjects of non-childbearing potential
- Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
- Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Demonstrate stable renal function
Exclusion Criteria:
- Renal allograft recipients
- Any condition possibly affecting drug absorption (eg, gastrectomy)
- A positive urine drug test
- History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
- Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer).
- Screening supine triplicate 12 lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS interval >120 msec
- Second-degree or third-degree AV block (unless paced) or baseline PR interval >180 msec at any time prior to dosing of study treatment.
- Abnormalities in clinical laboratory tests at screening
- Pregnant or breastfeeding female subjects
- History of HIV, Hepatitis B, Hepatitis C, HIT, sensitivity to heparin
- Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation
Sites / Locations
- Anaheim Clinical Trials, LLC
- Prism Clinical Research, LLC
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Other
Arm Label
Mild
Moderate
Severe
Normal
Arm Description
Mild renal impairment
Moderate renal impairment
Severe renal impairment
Normal renal function
Outcomes
Primary Outcome Measures
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib
AUCinf was calculated by AUClast + (Clast*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration; Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Maximum Observed Plasma Concentration (Cmax) of Lorlatinib
Cmax was observed directly from data.
Secondary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below.
Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormalities
The hematology, chemistry and urinalysis tests were included in the laboratory examination. Hematology evaluation included hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration and erythrocyte mean corpuscular hemoglobin. Chemistry evaluation included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein, lipase and amylase. Urinalysis evaluation included decimal logarithm of reciprocal of hydrogen ion activity [pH], glucose, protein, blood, ketones, microscopy, ketones, nitrite, leukocyte esterase, urobilinogen, urine bilirubin and bacteria. The lab abnormalities were reported in accordance with the sponsor reporting standards.
Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria
Vital signs evaluations included supine diastolic blood pressure (DBP), and supine systolic blood pressure (SBP) were measured with the participant's arm supported at the level of the heart and recorded to the nearest mmHg after approximately 5 minutes of rest. Number of participants with vital signs data meeting the categorical summarization criteria is presented. The pre-specified criteria of vital signs data were categorized as follows: SBP (minimum) <90 mmHg, maximum of decrease and increase from baseline for SBP >=30 mmHg; DBP (minimum) <50 mmHg, maximum of decrease and increase from baseline for DBP>=20 mmHg.
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria
ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), and QT interval corrected for heart rate using Fridericia's formula (QTcF interval). The pre-specified criteria of ESG data were categorized as below.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03542305
Brief Title
Lorlatinib Renal Impairment Study
Official Title
A PHASE 1, SINGLE DOSE OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS OF LORLATINIB IN SUBJECTS WITH IMPAIRED RENAL FUNCTION
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
August 23, 2018 (Actual)
Primary Completion Date
February 20, 2020 (Actual)
Study Completion Date
February 20, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1, open-label, multi-center, single treatment study in subjects with normal renal function and varying degrees of renal impairment.
Detailed Description
This is a Phase 1, open-label, multi-center, single treatment study in subjects with normal renal function and varying degrees of renal impairment. Each subject will receive a single oral dose of lorlatinib administered in the fasted state. Subjects with mild, moderate, and severe renal impairment will be enrolled and normal healthy subjects will be enrolled as matched controls.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mild
Arm Type
Experimental
Arm Description
Mild renal impairment
Arm Title
Moderate
Arm Type
Experimental
Arm Description
Moderate renal impairment
Arm Title
Severe
Arm Type
Experimental
Arm Description
Severe renal impairment
Arm Title
Normal
Arm Type
Other
Arm Description
Normal renal function
Intervention Type
Drug
Intervention Name(s)
Lorlatinib
Intervention Description
Lorlatinib single oral dose
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib
Description
AUCinf was calculated by AUClast + (Clast*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration; Clast* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Title
Maximum Observed Plasma Concentration (Cmax) of Lorlatinib
Description
Cmax was observed directly from data.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below.
Time Frame
Baseline up to 28 days after last dose of study treatment (approximately 29 days)
Title
Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormalities
Description
The hematology, chemistry and urinalysis tests were included in the laboratory examination. Hematology evaluation included hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration and erythrocyte mean corpuscular hemoglobin. Chemistry evaluation included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid albumin, total protein, lipase and amylase. Urinalysis evaluation included decimal logarithm of reciprocal of hydrogen ion activity [pH], glucose, protein, blood, ketones, microscopy, ketones, nitrite, leukocyte esterase, urobilinogen, urine bilirubin and bacteria. The lab abnormalities were reported in accordance with the sponsor reporting standards.
Time Frame
Screening, Day -1, Day 2 and Day 6
Title
Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria
Description
Vital signs evaluations included supine diastolic blood pressure (DBP), and supine systolic blood pressure (SBP) were measured with the participant's arm supported at the level of the heart and recorded to the nearest mmHg after approximately 5 minutes of rest. Number of participants with vital signs data meeting the categorical summarization criteria is presented. The pre-specified criteria of vital signs data were categorized as follows: SBP (minimum) <90 mmHg, maximum of decrease and increase from baseline for SBP >=30 mmHg; DBP (minimum) <50 mmHg, maximum of decrease and increase from baseline for DBP>=20 mmHg.
Time Frame
Baseline up to 28 days after last dose of study treatment (approximately 29 days)
Title
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria
Description
ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), and QT interval corrected for heart rate using Fridericia's formula (QTcF interval). The pre-specified criteria of ESG data were categorized as below.
Time Frame
Screening, Day -1, 0 hours (pre-dose), 1 hour, 2 hours, 4 hours, 24 hours and 120 hours postdose.
Other Pre-specified Outcome Measures:
Title
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Lorlatinib
Description
AUClast was calculated by linear/Log trapezoidal method.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Title
Time for Cmax (Tmax) of Lorlatinib
Description
Tmax was observed directly from data as time of first occurrence.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Title
Terminal Elimination Plasma Half-life (t½) of Lorlatinib
Description
t1/2 was calculated by ln(2)/kel.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Title
Apparent Clearance After Oral Dose (CL/F) of Lorlatinib
Description
CL/F was calculated by Dose/AUCinf.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Title
Apparent Volume of Distribution Following Oral Dose (Vz/F) of Lorlatinib
Description
Vz/F was calculated by Dose/(AUCinf*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Title
Renal Clearance (CLR) of Lorlatinib
Description
CLR was calculated by Ae/AUClast. Ae was cumulative amount of drug recovered unchanged in urine, which was calculated by sum of (urine concentration × sample volume) for each collection interval from 0 to time 120 hours postdose. Sample volume = (urine weight in g/1.020), where 1.020 g/mL is the approximate specific gravity of urine.
Time Frame
0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Female subjects of non-childbearing potential
Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb)
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study
Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
Demonstrate stable renal function
Exclusion Criteria:
Renal allograft recipients
Any condition possibly affecting drug absorption (eg, gastrectomy)
A positive urine drug test
History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months before screening.
Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product (whichever is longer).
Screening supine triplicate 12 lead ECG demonstrating a corrected QT (QTc) interval >450 msec or a QRS interval >120 msec
Second-degree or third-degree AV block (unless paced) or baseline PR interval >180 msec at any time prior to dosing of study treatment.
Abnormalities in clinical laboratory tests at screening
Pregnant or breastfeeding female subjects
History of HIV, Hepatitis B, Hepatitis C, HIT, sensitivity to heparin
Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Anaheim Clinical Trials, LLC
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Prism Clinical Research, LLC
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
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.
Citations:
PubMed Identifier
35018553
Citation
Lin S, Gong J, Canas GC, Winkle P, Pelletier K, LaBadie RR, Ginman K, Pithavala YK. A Phase I Study to Evaluate the Pharmacokinetics and Safety of Lorlatinib in Adults with Mild, Moderate, and Severe Renal Impairment. Eur J Drug Metab Pharmacokinet. 2022 Mar;47(2):235-245. doi: 10.1007/s13318-021-00747-4. Epub 2022 Jan 11. Erratum In: Eur J Drug Metab Pharmacokinet. 2022 Mar 8;:
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=B7461010
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
Lorlatinib Renal Impairment Study
We'll reach out to this number within 24 hrs