Pharmacokinetics of Lanraplenib in Adults With Impaired R... | NCT02959138

NCT02959138

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2016-003823-47	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Lanraplenib.	Drug	20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1	Mild Renal Impairment (Adaptive Cohort 3) Moderate Renal Impairment (Cohort 1)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events		Day 1 up to Day 31
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.

Eligibility Module

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.

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Pharmacology of Miami, Inc. (CPMI)		Miami	Florida		United States
Omega Research Consultants, LLC

PubMed Identifier	Type	Citation	Retractions
	Background	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.

ID	Title	Description
FG000	Moderate Renal Impairment	Participants with moderate renal impairment received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.
FG001	Severe Renal Impairment	Participants with severe renal impairment received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.
FG002	Healthy Control	Matched healthy control participants received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Moderate Renal Impairment	Participants with moderate renal impairment received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.
BG001	Severe Renal Impairment

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

PK Analysis Set included all enrolled participants who took study drug, had at least 1 nonmissing postdose concentration value reported by PK lab for corresponding analytes, based on CLcr. Some healthy control participants matched to participants with moderate renal impairment were also used as matches to participants with severe renal impairment.

Posted

Mean

Standard Deviation

h*ng/mL

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

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Moderate Renal Impairment	Participants with moderate renal impairment received a single oral dose of 20 mg lanraplenib tablets in a fasted state, on Day 1.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Amendment 1	Jan 9, 2017	Sep 9, 2019	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Feb 13, 2019	Sep 9, 2019	SAP_001.pdf

OG000	Cohort 1: Moderate Renal Impairment	Participants with moderate renal impairment received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.
OG001	Cohort 1: Healthy Control	Matched healthy control participants to moderate renal impairment cohort, received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.
OG002	Cohort 2: Severe Renal Impairment	Participants with severe renal impairment received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.
OG003	Cohort 2: Healthy Control	Matched healthy control participants to severe renal impairment cohort, received a single oral dose of lanraplenib 20 mg (2 x 10 mg tablets) in a fasted state, on Day 1.