Renal ImpairmentPhase 1NCT03542305

Lorlatinib Renal Impairment Study

A Phase 1 study testing Lorlatinib in people with Renal Impairment, run by Pfizer at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Renal Impairment
What is being tested?: Lorlatinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 2 sitesUnited States
Study dates: 23 Aug 2018to 20 Feb 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 11Show fewer

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Anaheim Clinical Trials, LLC
Anaheim, California, 92801
Prism Clinical Research, LLC
Saint Paul, Minnesota, 55114

Other trials in United States

About this study

Official title: A PHASE 1, SINGLE DOSE OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS OF LORLATINIB IN SUBJECTS WITH IMPAIRED RENAL FUNCTION

This is a Phase 1, open-label, multi-center, single treatment study in subjects with normal renal function and varying degrees of renal impairment.

Read the 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.

Conditions: Renal Impairment
Being tested: Lorlatinib
Medical subject headings: Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LorlatinibDrug
Lorlatinib single oral dose

Study groups in NCT03542305
Study group	Role	What they receive
Mild	Experimental	Mild renal impairment Receives: Drug: Lorlatinib
Moderate	Experimental	Moderate renal impairment Receives: Drug: Lorlatinib
Severe	Experimental	Severe renal impairment Receives: Drug: Lorlatinib
Normal	Other	Normal renal function Receives: Drug: Lorlatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Maximum Observed Plasma Concentration (Cmax) of Lorlatinib
Cmax was observed directly from data.
Measured: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose

Secondary outcomes (4)

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.
Measured: Baseline up to 28 days after last dose of study treatment (approximately 29 days)
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.
Measured: Screening, Day -1, Day 2 and Day 6
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.
Measured: Baseline up to 28 days after last dose of study treatment (approximately 29 days)
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.
Measured: Screening, Day -1, 0 hours (pre-dose), 1 hour, 2 hours, 4 hours, 24 hours and 120 hours postdose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Aug 201820 Feb 2020

First posted31 May 2018
Study start23 Aug 2018
Primary completion20 Feb 2020
Study completion20 Feb 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Renal ImpairmentStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03542305
Sponsor's protocol ID: B7461010
Other IDs: RENAL IMPAIRMENT
Status last verified: Feb 2021
First submitted: 18 May 2018
Last updated: 21 Feb 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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.

Publications

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.
PubMed 35018553

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Diuretic Tuner Clinical Decision Support
Edema, Hypervolemia
Not yet recruitingObservational study
Effect of Filter Lifespan in CRRT on New Infections in Critically Ill Patients With AKI
Acute Kidney Injury
Enrolling by invitationObservational study
ProNephro NGAL Test for Early Detection of Acute Kidney Injury in Adult ICU Patients (ALPACA)
Acute Kidney Injury
RecruitingObservational study
Immune System Related Kidney Disease
Kidney Disease, Nephrotic Syndrome
Recruiting
Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Chronic Kidney Disease (CKD)
Chronic Kidney Diseases

All Renal Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A PHASE 1, SINGLE DOSE OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS OF LORLATINIB IN SUBJECTS WITH IMPAIRED RENAL FUNCTION
ClinicalTrials.gov ID: NCT03542305
Acronym / sponsor ID: B7461010
Conditions: Renal Impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 23 Aug 2018 (actual)
Primary completion: 20 Feb 2020 (actual)
Study completion: 20 Feb 2020 (actual)
First posted: 31 May 2018 (actual)
Results: Posted 21 Feb 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Mild	Experimental	Drug: LorlatinibMild renal impairment
Moderate	Experimental	Drug: LorlatinibModerate renal impairment
Severe	Experimental	Drug: LorlatinibSevere renal impairment
Normal	Other	Drug: LorlatinibNormal renal function

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (11 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LorlatinibLorlatinib single oral dose	Drug	Mild, Moderate, Normal, Severe

Primary outcome

Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
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
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose
Cmax was observed directly from data.

4 secondary outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Baseline up to 28 days after last dose of study treatment (approximately 29 days)
Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormalities
Time frame: Screening, Day -1, Day 2 and Day 6
Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria
Time frame: Baseline up to 28 days after last dose of study treatment (approximately 29 days)
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria
Time frame: Screening, Day -1, 0 hours (pre-dose), 1 hour, 2 hours, 4 hours, 24 hours and 120 hours postdose.

Results and safety

Results posted to the registry on 21 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Normal Function	8	8
Mild Impairment	8	8
Moderate Impairment	8	8
Severe Impairment	5	5

Primary outcome: Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Normal Function n = 8	Mild Impairment n = 8	Moderate Impairment n = 8	Severe Impairment n = 5
Value	8329 (33)	8683 (29)	9890 (27)	11760 (37)

Normal Function vs Mild Impairment: Ratio (%) of Adjusted Geometric Means: 104.25 (90% CI 79.73 to 136.31), ANOVA
Normal Function vs Moderate Impairment: Ratio (%) of Adjusted Geometric Means: 118.75 (90% CI 91.43 to 154.24), ANOVA
Normal Function vs Severe Impairment: Ratio (%) of Adjusted Geometric Means: 141.14 (90% CI 97.82 to 203.66), ANOVA

Population analysed: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Lorlatinib

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Normal Function n = 8	Mild Impairment n = 8	Moderate Impairment n = 8	Severe Impairment n = 5
Value	546.8 (48)	549.7 (52)	485.9 (24)	504.8 (50)

Normal Function vs Mild Impairment: Ratio (%) of Adjusted Geometric Means: 100.53 (90% CI 66.48 to 152.02), ANOVA
Normal Function vs Moderate Impairment: Slope: 88.87 (90% CI 64.18 to 123.06), ANOVA
Normal Function vs Severe Impairment: Ratio (%) of Adjusted Geometric Means: 92.32 (90% CI 56.58 to 150.63), ANOVA

Population analysed: The analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline up to 28 days after last dose of study treatment (approximately 29 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal Function	0 of 8 (0%)	5 of 8 (62.5%)	0 of 8
Mild Impairment	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Moderate Impairment	0 of 8 (0%)	4 of 8 (50%)	0 of 8
Severe Impairment	0 of 5 (0%)	1 of 5 (20%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35018553Lin 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.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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.

Related trials for Renal Impairment

Recruiting
Diuretic Tuner Clinical Decision Support
Edema, Hypervolemia
Not yet recruitingObservational study
Effect of Filter Lifespan in CRRT on New Infections in Critically Ill Patients With AKI
Acute Kidney Injury
Enrolling by invitationObservational study
ProNephro NGAL Test for Early Detection of Acute Kidney Injury in Adult ICU Patients (ALPACA)
Acute Kidney Injury
RecruitingObservational study
Immune System Related Kidney Disease
Kidney Disease, Nephrotic Syndrome
Recruiting
Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Chronic Kidney Disease (CKD)
Chronic Kidney Diseases

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Lorlatinib in people with Renal Impairment, run by Pfizer at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Lorlatinib (time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03542305, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.