Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function

NCT02959138 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-379-19322016-003823-47
• Study Type: interventional
• Target: 36
• Locations: 3 countries
• Sites: 6

Brief 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.

Conditions

Inflammatory Disease

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (2)

• Percentage of Participants Who Experienced Treatment-Emergent Adverse Events

  Day 1 up to Day 31

• Percentage of Participants Who Experienced Graded Laboratory Abnormalities

  Day 1 up to Day 31

Study Arms (3)

Moderate Renal Impairment (Cohort 1)

EXPERIMENTAL

Participants with moderate renal impairment and matched healthy controls will receive a single dose of lanraplenib

Drug: Lanraplenib.

Severe Renal Impairment (Adaptive Cohort 2)

EXPERIMENTAL

Participants with severe renal impairment and matched healthy controls will receive a single dose of lanraplenib

Drug: Lanraplenib.

Mild Renal Impairment (Adaptive Cohort 3)

EXPERIMENTAL

Participants with mild renal impairment and matched healthy controls will receive a single dose of lanraplenib

Drug: Lanraplenib.

Interventions

Lanraplenib. DRUG

20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1

Also known as: GS-9876

Mild Renal Impairment (Adaptive Cohort 3); Moderate Renal Impairment (Cohort 1); Severe Renal Impairment (Adaptive Cohort 2)

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

Clinical Pharmacology of Miami, Inc. (CPMI)

Miami, Florida, United States

Location

Omega Research Consultants, LLC

Orlando, Florida, United States

Location

Orlando Clinical Research Center

Orlando, Florida, United States

Location

APEX GmBH

Munich, Germany

Location

Auckland Clinical Studies

Grafton, Auckland, New Zealand

Location

Christchurch Clinical Studies Trust

Christchurch, New Zealand

Location

Related 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.

  BACKGROUND

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  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: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2016
• First Posted: November 8, 2016
• Study Start: November 21, 2016
• Primary Completion: October 5, 2018
• Study Completion: October 5, 2018
• Last Updated: October 25, 2019
• Results First Posted: October 25, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); DE (1); NZ (2)