A Study to Investigate the Pharmacokinetics, Safety, and... | NCT03277755

ID	Type	Description	Link
64294178HPC1020	Other Identifier	Janssen Research & Development, LLC

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort1:Participants With Moderately Impaired Hepatic Function	Experimental	Participants With moderately impaired hepatic function will receive a single oral dose of AL-335 800 milligram (mg) (2 tablets of 400 mg AL-335) on Day 1 of Part 1 followed by a single oral dose of odalasvir (ODV) 25 mg (1 tablet of 25 mg ODV) on Day 8 of Part 1 and a combination of AL-335 800 mg (2 tablets of 400 mg AL-335) + ODV 25 mg (1 tablet of 25 mg ODV) + simeprevir (SMV) 75 mg (1 capsule of 75 mg SMV) once daily on Day 1 to 14 of Part 2. There will be a washout period between Part 1 and Part 2 of at least 14 days. Day 8 of Part 1 will be the start of the washout period. Prior to the start of study drug administration in Part 2, a safety review will be performed by the Sponsor.	Drug: AL-335 800 mg Drug: ODV 25 mg Drug: SMV 75 mg
Cohort 2: Participants With Normal Hepatic Function	Experimental	Participants with normal hepatic function will receive a single oral dose of AL-335 800 mg (2 tablets of 400 mg AL-335) on Day 1 of Part 1 followed by a single oral dose of ODV 25 mg (1 tablet of 25 mg ODV) on Day 8 of Part 1 and a combination of AL-335 800 mg (2 tablets of 400 mg AL-335) + ODV 25 mg (1 tablet of 25 mg ODV) + SMV 75 mg (1 capsule of 75 mg SMV) once daily on Day 1 to 14 of Part 2. There will be a washout period between Part 1 and Part 2 of at least 14 days. Day 8 of Part 1 will be the start of the washout period. Prior to the start of study drug administration in Part 2, a safety review will be performed by the Sponsor.	Drug: AL-335 800 mg Drug: ODV 25 mg Drug: SMV 75 mg

Interventions

Name	Type	Description	Arm Group Labels	Other Names
AL-335 800 mg	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	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.	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

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participant must have a body mass index (BMI; weight in kilogram (kg) divided by the square of height in meters) of 18.0 to 35.0 kilogram per meter square (kg/m^2) extremes included, and a body weight not less than 50.0 kg
Participant must have a normal 12-lead electrocardiogram (ECG) (based on the mean value of triplicate ECG parameters) consistent with normal cardiac conduction and function at screening, as defined in the protocol
Absence of findings indicative of hepatocellular carcinoma in an ultrasonography determined within 90 days prior to screening (or between screening and Day -1 of Part 1 of the study)
Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies; a female participant with non childbearing potential must be; a) postmenopausal, or b) surgically sterile. Participant of childbearing potential must; a) have a negative highly sensitive serum (beta human chorionic gonadotropin [beta hCG]) pregnancy test at screening and a negative urine beta hCG pregnancy test at baseline (Day -1), and b) not get pregnant from screening until at least 60 days after the end of treatment by adhering to one of the acceptable methods of birth control to avoid pregnancy
Contraceptive use by men should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies: A male participant: a) must either be surgically sterile, or b) must not be heterosexually active from baseline until at least 60 days after the end of treatment or c) must be practicing an acceptable method of birth control from baseline until at least 60 days after the end of treatment, if heterosexually active with a woman of childbearing potential
Participants with moderately impaired hepatic function (Cohort 1) must meet the following additional inclusion criteria:
1. Participants must have a stable hepatic function as confirmed by serum bilirubin, serum albumin, prothrombin, ascites, and hepatic encephalopathy status measured during screening and those measured within 24 hours prior to first study drug administration on Day 1 in Part 1
2. Participants must be hepatically impaired with a Class B classification as defined by the Child Pugh classification of severity of liver disease, that is, a total Child-Pugh score of 7 to 9, inclusive.
Participants with normal hepatic function (Cohort 2) must meet the additional inclusion criteria to be enrolled in the study: Participants must have a normal hepatic function as confirmed by serum bilirubin, serum albumin, prothrombin, ascites, and hepatic encephalopathy status measured during screening and those measured within 24 hours prior to first study drug administration on Day 1 in Part 1

Exclusion Criteria:

Participant has either: a history of renal insufficiency (estimated creatinine clearance lesser than (<) 90 milliliter per minute per 1.73 meter square (mL/min/1.73m^2) for estimated glomerular filtration rate [eGFR] according to the Chronic Kidney Disease Epidemiology Collaboration [CKD- EPI] equation) 18, or serum creatinine grade 1 or greater than (>) 1.1* upper limit of normal [ULN]) during screening
Participant has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (example, compromise the well-being), or that could prevent, limit, or confound the protocol-specified assessments
Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticarial
Participant has known allergies, hypersensitivity, or intolerance to simeprevir (SMV), odalasvir (ODV), or AL 335, or their excipients
Participant who smokes more than 10 cigarettes or 2 cigars or 2 pipes per day from within 90 days before screening until the end of the study

ID	Term
C000629483	adafosbuvir
D000069468	Desvenlafaxine Succinate

ID	Term
D003511	Cyclohexanols
D000441	Hexanols
D005233	Fatty Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D003510	Cyclohexanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D010636	Phenols
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D008055	Lipids