Clinical trial NCT02959138: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Inflammatory Disease
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-11-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUClast of Lanraplenib Presented Based on Range of CLcr
timeFrame: 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
measure: PK Parameter: AUCinf of Lanraplenib Presented Based on Range of CLcr
timeFrame: 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
measure: PK Parameter: Cmax of Lanraplenib Presented Based on Range of CLcr
timeFrame: 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:
measure: Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
timeFrame: Day 1 up to Day 31
measure: Percentage of Participants Who Experienced Graded Laboratory Abnormalities
timeFrame: Day 1 up to Day 31
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami, Inc. (CPMI)
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Munich
country: Germany
facility: APEX GmBH
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Clinical Studies Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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.