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Study to Investigate the Pharmacokinetic Interaction Between 2 Direct Acting Antiviral Agents Odalasvir and AL-335 and Between 3 Direct Acting Antiviral Agents Simeprevir, Odalasvir and AL-335 at Steady State in Healthy Japanese Participants

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ClinicalTrials.gov Identifier: NCT02824315
Recruitment Status : Completed
First Posted : July 6, 2016
Last Update Posted : December 1, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to investigate the steady-state pharmacokinetics (PK) of simeprevir (SMV), odalasvir (ODV) and AL-335 (and its metabolites ALS-022399 and ALS 022227), when these drugs are co-administered in healthy Japanese participants.

Condition or disease Intervention/treatment Phase
Healthy Drug: AL-335 Drug: Odalasvir (ODV) Drug: Simeprevir (SMV) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Fixed Sequence Study to Investigate the Pharmacokinetic Interaction Between 2 Direct Acting Antiviral Agents Odalasvir and AL-335 and Between 3 Direct Acting Antiviral Agents Simeprevir, Odalasvir and AL-335 at Steady State in Healthy Japanese Subjects
Study Start Date : May 2016
Actual Primary Completion Date : October 2016
Actual Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Simeprevir

Arm Intervention/treatment
Experimental: AL-335+Simeprevir (SMV)+Odalasvir (ODV)
Participants will receive AL-335 800 milligram (mg) once daily from day 1-3; SMV 75 mg once daily from Day 4-13; loading dose of ODV 150 mg on Day 14, followed by ODV 50 mg once daily from Day 15 to 23; ODV 50 mg once daily + AL-335 800 mg once daily from day 24-26; ODV 50 mg once daily + SMV 75 mg once daily from Day 27-33 and ODV 50 mg once daily + SMV 75 mg once daily + AL-335 800 mg once daily from Day 34 to 36.
Drug: AL-335
AL--335 800 mg once daily on Days 1--3, 24--26 and 34--36.

Drug: Odalasvir (ODV)
ODV 150 mg on Day 14 and 50 mg once daily on Days 15--23, 24--26, 27--33 and 34--36.

Drug: Simeprevir (SMV)
Simeprevir 75 mg once daily on Days 4-13, 27--33 and 34--36.




Primary Outcome Measures :
  1. Average Analyte Concentration at Steady State (Cavg,ss) [ Time Frame: Up to Day 36 ]
    The Cavg,ss is calculated as area under the plasma concentration-time curve during a dosing Interval (AUC[tau]) divided by the dosing interval (tau).

  2. Maximum Observed Analyte Concentration (Cmax) [ Time Frame: Up to Day 36 ]
    The Cmax is the maximum observed analyte concentration.

  3. Minimum Observed Analyte Concentration (Cmin) [ Time Frame: Up to Day 36 ]
    The Cmin is the minimum observed analyte concentration during dosing interval.

  4. Trough Plasma Concentration (Ctrough) [ Time Frame: Up to Day 36 ]
    The (Ctrough) is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose in a multiple dosing regimen.

  5. Time to Reach Maximum Observed Analyte Concentration (Tmax) [ Time Frame: Up to Day 36 ]
    The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

  6. Area Under the Analyte Concentration-Time Curve From Time 0 to 24 Hours (AUC24) [ Time Frame: Up to Day 36 ]
    The AUC24 is the area under the analyte concentration-time curve from time 0 to 24 hours.

  7. Fluctuation Index (FI) [ Time Frame: Up to Day 36 ]
    Fluctuation Index is defined as percentage of fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax-Cmin]/Cavg).

  8. Area Under the Analyte Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) [ Time Frame: Up to Day 36 ]
    The (AUC [0-last]) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration.

  9. Area Under the Analyte Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) [ Time Frame: Up to Day 36 ]
    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.

  10. Elimination Rate Constant (Lambda[z]) [ Time Frame: Up to Day 36 ]
    Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

  11. Elimination Half-Life (t1/2) [ Time Frame: Up to Day 36 ]
    Elimination half-life (t[1/2]) is associated with the terminal slope (lambda [z]) of the semi-logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability [ Time Frame: Up to Follow-up (170 to 175 days after last study drug intake) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant must be a Japanese participant who has resided outside Japan for no more than 5 years and whose parents and grandparents are Japanese as determined by participant's verbal report
  • Participant must have a body mass index (BMI: weight in kilogram (kg) divided by the square of height in meters) of 18.0 to 30.0 kilogram per meter square (kg/m^2), extremes included, and a body weight not less than 50.0 kg
  • Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening. If there are abnormalities, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the Investigator
  • Participant must have a blood pressure (after the participant is supine for 5 minutes) between 90 and 140 milligram of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic. If blood pressure is out of range, up to 2 repeated assessments are permitted
  • Female participant must agree to not donate eggs (ova, oocytes) for the purpose of assisted reproduction during the study and for a period of 60 days after last study drug administration or until the last follow-up visit, whichever occurs later

Exclusion Criteria:

  • Participant has a history of liver or renal insufficiency (estimated creatinine clearance below 80 milliliters per minute [mL/min]); significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
  • Participant with a past history of heart arrhythmias (example- extra systolic beats or tachycardia at rest); risk factors associated with Torsade de Pointes such as hypokalemia or family history of short/long QT syndrome or sudden unexplained death (including sudden infant death syndrome) in a first degree relative [example- sibling, offspring, or biological parent])
  • Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
  • Participant has known allergies, hypersensitivity, or intolerance to simeprevir (SMV), odalasvir (ODV), AL-335 or their excipients
  • Participant is a woman who is pregnant, or breast-feeding, or planning to become pregnant from signing of Informed Consent Form (ICF) until 60 days after last study drug administration or until the last follow-up visit, whichever occurs later

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02824315


Locations
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United Kingdom
Surrey, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02824315    
Other Study ID Numbers: CR108179
64294178HPC1006 ( Other Identifier: Janssen Research & Development, LLC )
2016-000950-36 ( EudraCT Number )
First Posted: July 6, 2016    Key Record Dates
Last Update Posted: December 1, 2016
Last Verified: November 2016
Additional relevant MeSH terms:
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Simeprevir
Odalasvir
Antiviral Agents
Anti-Infective Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action