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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
20 mg (2 X 10 mg) tablets administered orally in a fasted state on Day 1
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
APEX GmBH
Munich, Germany
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
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
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
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
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
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Auckland Clinical Studies
Grafton, Auckland, New Zealand
Christchurch Clinical Studies Trust
Christchurch, New Zealand
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
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
Time frame: 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.
Time frame: Day 1 up to Day 31