Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function

Inflammatory Disease Clinical Trial

Official title:

A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of GS-9876 in Subjects With Impaired Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02959138
• Other study ID #: GS-US-379-1932
• Secondary ID: 2016-003823-47
• Status: Completed
• Phase: Phase 1
• Start date: November 21, 2016
• Est. completion date: October 5, 2018

Study information

• Verified date: October 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the pharmacokinetics (PK) of lanraplenib in participants with impaired renal function relative to matched healthy controls. Participants in this study will be enrolled using an adaptive design that includes up to 3 enrolled cohorts. Based on safety and/or PK data in Cohort 1, participants will be enrolled in adaptive Cohorts 2 and/or 3.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: October 5, 2018
• Est. primary completion date: October 5, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

All Individuals

• Have the ability to understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of study procedures

• Have a calculated body mass index (BMI) of = 18 kg/m^2 and = 36 kg/m^2 at screening

• Females of childbearing potential must have a negative pregnancy test at screening and clinic admission (Day -1).

• Individuals have not donated blood within 56 days of study entry or plasma within 7 days of study entry and must refrain from blood donation from clinic admission, throughout the study period, and continuing for at least 30 days following the last dose of study drug.

• Have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the sponsor

• Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs

For Individuals with Renal Impairment

• Must have diagnosis of chronic (> 6 months), stable renal impairment with no clinically significant change in renal function status within 90 days prior to study drug administration (Day 1).

• Have a creatinine clearance (CLcr) < 90 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening.

For Healthy Matched Controlled Individuals (Individuals with Normal Renal Function)

• Have a CLcr = 90 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at screening

• Match in age (± 10 years), gender, and body mass index (± 20%, 18 kg/m^2 = BMI = 36 kg/m^2).

Key Exclusion Criteria:

• Be a lactating female

• Have received any investigational compound within 30 days prior to study dosing

• Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance or individual's safety as judged by the investigator

• Have a positive test result for human immunodeficiency virus type 1 (HIV-1) antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody

• Have poor venous access that limits phlebotomy

For Individuals with Renal Impairment

• Require or are anticipated to require dialysis within 90 days of study dosing

• Require during the study or have received moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A within 2 weeks prior to study drug administration.

For Healthy Matched Controlled Individuals (Individuals with Normal Renal Function)

• Have taken any prescription medications or over-the-counter medications, including herbal products and antacids, within 28 days prior to start of study drug dosing, with the exception of vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications and/or stable hormone replacement therapy in peri- /post-menopausal female

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Inflammatory Disease
• Renal Insufficiency

Intervention

Drug:
• Lanraplenib.
20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1

Locations

Country	Name	City	State
Germany	APEX GmBH	Munich
New Zealand	Christchurch Clinical Studies Trust	Christchurch
New Zealand	Auckland Clinical Studies	Grafton	Auckland
United States	Clinical Pharmacology of Miami, Inc. (CPMI)	Miami	Florida
United States	Omega Research Consultants, LLC	Orlando	Florida
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Germany,  New Zealand, 

References & Publications (1)

Hsueh CH, Zheng H, Matzkies F, Mozaffarian A, Medzihradsky O, Tarnowski T, Curry N, and Mathias A. Pharmacokinetics and Short-Term Safety of GS-9876, an Oral Spleen Tyrosine Kinase Inhibitor in Subjects with Renal Impairment. American Society for Clinical Pharmacology and Therapeutics 2019; Washington D.C.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) Parameter: AUClast of Lanraplenib Presented Based on Range of CLcr	AUClast is defined as the concentration of drug from time zero to the last observable concentration. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = ([140-age in years] × [body weight in kg])/(72 × serum creatinine in mg/dL); For women: CLcr (mL/min) = 0.85 × ([140-age in years] × [body weight in kg])/(72 × serum creatinine in mg/dL); Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min; Severe renal impairment: CLcr 15-29 mL/min; Healthy control: CLcr = 90 mL/min	0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96 and 120 hours postdose on Day 1
Primary	PK Parameter: AUCinf of Lanraplenib Presented Based on Range of CLcr	AUCinf is defined as the concentration of drug extrapolated to infinite time. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = ([140-age in years] × [body weight in kg])/(72 × serum creatinine in mg/dL); For women: CLcr (mL/min) = 0.85 × ([140-age in years] × [body weight in kg])/(72 × serum creatinine in mg/dL); Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min; Severe renal impairment: CLcr 15-29 mL/min; Healthy control: CLcr = 90 mL/min	0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96 and 120 hours postdose on Day 1
Primary	PK Parameter: Cmax of Lanraplenib Presented Based on Range of CLcr	Cmax is defined as the maximum concentration of drug. CLcr was estimated using the CG equation for renal function as recommended by the FDA and international guidance documents. CG equation: For men: CLcr (mL/min) = ([140-age in years] × [body weight in kg])/(72 × serum creatinine in mg/dL); For women: CLcr (mL/min) = 0.85 × ([140-age in years] × [body weight in kg])/(72 × serum creatinine in mg/dL); Participants were classified based on estimated CLcr as: Moderate renal impairment: CLcr 30-59 mL/min; Severe renal impairment: CLcr 15-29 mL/min; Healthy control: CLcr = 90 mL/min	0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 60, 72, 96 and 120 hours postdose on Day 1
Secondary	Percentage of Participants Who Experienced Treatment-Emergent Adverse Events		Day 1 up to Day 31
Secondary	Percentage of Participants Who Experienced Graded Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. The criteria used for grading was Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.	Day 1 up to Day 31