The purpose of this study is to evaluate the pharmacokinetics (PK) of AL-335, odalasvir (ODV) and its metabolites ALS-022399 and ALS-022227, after a single oral dose of ODV and AL-335 respectively, in participants with moderately impaired hepatic function compared to participants with normal hepatic function. Also to evaluate the steady-state PK of AL-335 and its metabolites ALS-022399 and ALS-022227, ODV and simeprevir (SMV) after multiple oral doses of the combination of AL-335+ODV+SMV, in participants with moderately impaired hepatic function compared to participants with normal hepatic function.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Participants will receive AL-335 800 mg (2 tablets of 400 mg AL-335) single oral dose on Day 1 of part 1 and in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.
Participants will receive ODV 25 mg (1 tablet of 25 mg ODV) single oral dose on Day 8 of part 1 and in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.
Participants will receive SMV 75 mg in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.
Part 1: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolites ALS-022399 and ALS-022227
Cmax is defined as maximum observed plasma concentration of AL-335 and its metabolites ALS-022399 and ALS-022227.
Time frame: Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of AL-335 and its Metabolites ALS-022399 and ALS-022227
The AUC (0-last) is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Time frame: Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335 and its Metabolites ALS-022399 and ALS-022227
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C (last)/ lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Time frame: Day 1: Predose, at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours postdose
Part 1: Maximum Observed Plasma Concentration (Cmax) of Odalasvir (ODV)
Cmax is defined as maximum observed plasma concentration of ODV.
Time frame: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC [0-last]) of ODV
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The AUC (0-last) is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Time frame: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC (last) and C (last)/lambda(z); wherein AUC (last) is area under the plasma concentration-time curve from time zero to the time of the last measurable concentration, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Time frame: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Part 2: Maximum Observed Plasma Concentration (Cmax) of Simeprevir (SMV)
Cmax is defined as maximum observed plasma concentration of SMV.
Time frame: Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose
Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Postdose (AUC[0-24]) of SMV
The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.
Time frame: Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose
Part 2: Maximum Observed Plasma Concentration (Cmax) of ODV
Cmax is defined as maximum observed plasma concentration of ODV.
Time frame: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours Postdose (AUC[0-24]) of ODV
The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.
Time frame: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose
Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C (last)/ lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Time frame: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose
Part 2: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolites ALS-022399 and ALS-022227
Cmax is defined as maximum observed plasma concentration of AL-335 and its metabolites ALS-022399 and ALS-022227.
Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose
Part 2: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC[0-24]) Postdose of AL-335 and its metabolites ALS-022399 and ALS-022227
The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose, calculated by linear-linear trapezoidal summation.
Time frame: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose
Part 1 and 2: Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.
Time frame: Up to 30-35 days after last drug intake (approximately up to 102 days)