The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02959138




Registration number
NCT02959138
Ethics application status
Date submitted
7/11/2016
Date registered
8/11/2016
Date last updated
25/10/2019

Titles & IDs
Public title
Pharmacokinetics of Lanraplenib in Adults With Impaired Renal Function
Scientific title
A Phase 1 Open-Label Study to Evaluate the Pharmacokinetics of GS-9876 in Subjects With Impaired Renal Function
Secondary ID [1] 0 0
2016-003823-47
Secondary ID [2] 0 0
GS-US-379-1932
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammatory Disease 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lanraplenib.

Experimental: Moderate Renal Impairment (Cohort 1) - Participants with moderate renal impairment and matched healthy controls will receive a single dose of lanraplenib

Experimental: Severe Renal Impairment (Adaptive Cohort 2) - Participants with severe renal impairment and matched healthy controls will receive a single dose of lanraplenib

Experimental: Mild Renal Impairment (Adaptive Cohort 3) - Participants with mild renal impairment and matched healthy controls will receive a single dose of lanraplenib


Treatment: Drugs: Lanraplenib.
20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
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
Timepoint [3] 0 0
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 [1] 0 0
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
Timepoint [1] 0 0
Day 1 up to Day 31
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Day 1 up to Day 31

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
Germany
State/province [2] 0 0
Munich
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland
Country [4] 0 0
New Zealand
State/province [4] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02959138
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications