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Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function

Primary Purpose

Inflammatory Disease

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Lanraplenib.
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Clinical Pharmacology of Miami, Inc. (CPMI)
  • Omega Research Consultants, LLC
  • Orlando Clinical Research Center
  • APEX GmBH
  • Auckland Clinical Studies
  • Christchurch Clinical Studies Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Moderate Renal Impairment (Cohort 1)

Severe Renal Impairment (Adaptive Cohort 2)

Mild Renal Impairment (Adaptive Cohort 3)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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
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
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

Secondary Outcome Measures

Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
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.

Full Information

First Posted
November 7, 2016
Last Updated
October 3, 2019
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02959138
Brief Title
Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function
Official Title
A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of GS-9876 in Subjects With Impaired Renal Function
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
November 21, 2016 (Actual)
Primary Completion Date
October 5, 2018 (Actual)
Study Completion Date
October 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Moderate Renal Impairment (Cohort 1)
Arm Type
Experimental
Arm Description
Participants with moderate renal impairment and matched healthy controls will receive a single dose of lanraplenib
Arm Title
Severe Renal Impairment (Adaptive Cohort 2)
Arm Type
Experimental
Arm Description
Participants with severe renal impairment and matched healthy controls will receive a single dose of lanraplenib
Arm Title
Mild Renal Impairment (Adaptive Cohort 3)
Arm Type
Experimental
Arm Description
Participants with mild renal impairment and matched healthy controls will receive a single dose of lanraplenib
Intervention Type
Drug
Intervention Name(s)
Lanraplenib.
Other Intervention Name(s)
GS-9876
Intervention Description
20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1
Primary Outcome Measure Information:
Title
Pharmacokinetic (PK) Parameter: AUClast of Lanraplenib Presented Based on Range of CLcr
Description
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
Time Frame
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
Title
PK Parameter: AUCinf of Lanraplenib Presented Based on Range of CLcr
Description
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
Time Frame
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
Title
PK Parameter: Cmax of Lanraplenib Presented Based on Range of CLcr
Description
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
Time Frame
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 Outcome Measure Information:
Title
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
Time Frame
Day 1 up to Day 31
Title
Percentage of Participants Who Experienced Graded Laboratory Abnormalities
Description
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.
Time Frame
Day 1 up to Day 31

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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Pharmacology of Miami, Inc. (CPMI)
City
Miami
State/Province
Florida
Country
United States
Facility Name
Omega Research Consultants, LLC
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
Country
United States
Facility Name
APEX GmBH
City
Munich
Country
Germany
Facility Name
Auckland Clinical Studies
City
Grafton
State/Province
Auckland
Country
New Zealand
Facility Name
Christchurch Clinical Studies Trust
City
Christchurch
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
Citation
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.
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Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function

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