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Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function

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ClinicalTrials.gov Identifier: NCT02959138
Recruitment Status : Completed
First Posted : November 8, 2016
Results First Posted : October 25, 2019
Last Update Posted : October 25, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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.

Condition or disease Intervention/treatment Phase
Inflammatory Disease Drug: Lanraplenib. Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of GS-9876 in Subjects With Impaired Renal Function
Actual Study Start Date : November 21, 2016
Actual Primary Completion Date : October 5, 2018
Actual Study Completion Date : October 5, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

Arm Intervention/treatment
Experimental: Moderate Renal Impairment (Cohort 1)
Participants with moderate renal impairment and matched healthy controls will receive a single dose of lanraplenib
Drug: Lanraplenib.
20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1
Other Name: GS-9876

Experimental: Severe Renal Impairment (Adaptive Cohort 2)
Participants with severe renal impairment and matched healthy controls will receive a single dose of lanraplenib
Drug: Lanraplenib.
20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1
Other Name: GS-9876

Experimental: Mild Renal Impairment (Adaptive Cohort 3)
Participants with mild renal impairment and matched healthy controls will receive a single dose of lanraplenib
Drug: Lanraplenib.
20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1
Other Name: GS-9876




Primary Outcome Measures :
  1. Pharmacokinetic (PK) Parameter: AUClast of Lanraplenib Presented Based on Range of CLcr [ 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 ]

    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


  2. PK Parameter: AUCinf of Lanraplenib Presented Based on Range of CLcr [ 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 ]

    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


  3. PK Parameter: Cmax of Lanraplenib Presented Based on Range of CLcr [ 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 ]

    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 :
  1. Percentage of Participants Who Experienced Treatment-Emergent Adverse Events [ Time Frame: Day 1 up to Day 31 ]
  2. Percentage of Participants Who Experienced Graded Laboratory Abnormalities [ Time Frame: Day 1 up to Day 31 ]
    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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02959138


Locations
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United States, Florida
Clinical Pharmacology of Miami, Inc. (CPMI)
Miami, Florida, United States
Omega Research Consultants, LLC
Orlando, Florida, United States
Orlando Clinical Research Center
Orlando, Florida, United States
Germany
APEX GmBH
Munich, Germany
New Zealand
Auckland Clinical Studies
Grafton, Auckland, New Zealand
Christchurch Clinical Studies Trust
Christchurch, New Zealand
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol: Amendment 1  [PDF] January 9, 2017
Statistical Analysis Plan  [PDF] February 13, 2019


Publications:
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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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02959138     History of Changes
Other Study ID Numbers: GS-US-379-1932
2016-003823-47 ( EudraCT Number )
First Posted: November 8, 2016    Key Record Dates
Results First Posted: October 25, 2019
Last Update Posted: October 25, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases