Lorlatinib Renal Impairment Study

NCT03542305 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: B7461010RENAL IMPAIRMENT
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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

  Screening, Day -1, Day 2 and Day 6

• Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria

  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

  Screening, Day -1, 0 hours (pre-dose), 1 hour, 2 hours, 4 hours, 24 hours and 120 hours postdose.

Other Outcomes (6)

• Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Lorlatinib

  0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose

• Time for Cmax (Tmax) of Lorlatinib

  0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose

• Terminal Elimination Plasma Half-life (t½) of Lorlatinib

  0 (pre-dose), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose

Study Arms (4)

Mild

EXPERIMENTAL

Mild renal impairment

Drug: Lorlatinib

Moderate

EXPERIMENTAL

Moderate renal impairment

Drug: Lorlatinib

Severe

EXPERIMENTAL

Severe renal impairment

Drug: Lorlatinib

Normal

OTHER

Normal renal function

Drug: Lorlatinib

Interventions

Lorlatinib DRUG

Lorlatinib single oral dose

Mild; Moderate; Normal; Severe

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Prism Clinical Research, LLC

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (1)

• 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.

  PMID: 35018553 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Renal Insufficiency

Interventions

lorlatinib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: May 31, 2018
• Study Start: August 23, 2018
• Primary Completion: February 20, 2020
• Study Completion: February 20, 2020
• Last Updated: February 21, 2021
• Results First Posted: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)