Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Inflammatory Disease

Treatments: Drug: Lanraplenib.

Study type: Interventional

Funder types: Industry

Identifiers

NCT02959138

GS-US-379-1932

2016-003823-47 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

Moderate Renal Impairment (Cohort 1)

Experimental group

Description:

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

Treatment:

Drug: Lanraplenib.

Severe Renal Impairment (Adaptive Cohort 2)

Experimental group

Description:

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

Treatment:

Drug: Lanraplenib.

Mild Renal Impairment (Adaptive Cohort 3)

Experimental group

Description:

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

Treatment:

Drug: Lanraplenib.