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Hepatic ImpairmentPhase 1NCT03277755

A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Odalasvir and AL-335 Alone and in Combination With Simeprevir in Participants With Moderately Impaired Hepatic Function

A Phase 1 study testing AL-335 800 mg, ODV 25 mg and SMV 75 mg in people with Hepatic Impairment, run by Janssen Research & Development, LLC.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Hepatic Impairment
What is being tested?
AL-335 800 mg, ODV 25 mg and SMV 75 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
11 Sep 2017to 22 Dec 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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
  • 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

Who cannot join

  • 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

About this study

Official title: An Open-label Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Odalasvir and AL-335 Alone and in Combination With Simeprevir in Subjects With Moderately Impaired Hepatic Function

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.

Being tested
AL-335 800 mg, ODV 25 mg, SMV 75 mg

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AL-335 800 mgDrug

    Also called JNJ-64146212

    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.

  • ODV 25 mgDrug

    Also called JNJ-64289901

    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.

  • SMV 75 mgDrug

    Participants will receive SMV 75 mg in combination as AL-335 + ODV + SMV once daily orally from Day 1 to 14 of part 2.

Study groups in NCT03277755
Study groupRoleWhat they receive
Cohort1:Participants With Moderately Impaired Hepatic FunctionExperimentalParticipants 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.
Receives: Drug: AL-335 800 mg; Drug: ODV 25 mg; Drug: SMV 75 mg
Cohort 2: Participants With Normal Hepatic FunctionExperimentalParticipants 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.
Receives: Drug: AL-335 800 mg; Drug: ODV 25 mg; Drug: SMV 75 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: 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

  4. Part 1: Maximum Observed Plasma Concentration (Cmax) of Odalasvir (ODV)

    Cmax is defined as maximum observed plasma concentration of ODV.

    Measured: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose

  5. 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

    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.

    Measured: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose

  6. 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.

    Measured: Day 8: Predose, at 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose

  7. Part 2: Maximum Observed Plasma Concentration (Cmax) of Simeprevir (SMV)

    Cmax is defined as maximum observed plasma concentration of SMV.

    Measured: Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose

  8. 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.

    Measured: Day 14: Predose, 1, 2, 4, 6, 8, 10, 12, 16 and 24 hours postdose

  9. Part 2: Maximum Observed Plasma Concentration (Cmax) of ODV

    Cmax is defined as maximum observed plasma concentration of ODV.

    Measured: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose

  10. 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.

    Measured: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose

  11. 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.

    Measured: Day 14: Predose, 1, 3, 4, 5, 6, 7, 8, 12, 16 and 24 postdose

  12. 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.

    Measured: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose

  13. 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.

    Measured: Day 14: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours postdose

Secondary outcomes (1)

  1. 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.

    Measured: Up to 30-35 days after last drug intake (approximately up to 102 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2017
  2. Study start11 Sep 2017 (estimated)
  3. Primary completion22 Dec 2017 (estimated)
  4. Study completion22 Dec 2017 (estimated)

Why it stopped: Development program of JNJ-4178 was discontinued.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03277755
Sponsor's protocol ID
CR108294
Other IDs
64294178HPC1020
Status last verified
Oct 2017
First submitted
8 Sep 2017
Last updated
11 Oct 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AL-335 800 mg, ODV 25 mg and SMV 75 mg in people with Hepatic Impairment, run by Janssen Research & Development, LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Maximum Observed Plasma Concentration (Cmax) 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). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03277755.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2017.

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