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

Lead sponsor

Janssen Research & Development, LLC is the lead sponsor of 929 studies on the registry; 76 are open to participants now.

Of its 283 completed or terminated interventional studies of FDA-regulated products, 134 (47%) have results posted.

Study arms

• 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 · Drug: Odalasvir (ODV) · Drug: Simeprevir (SMV)

Interventions

• DrugAL-335

  AL--335 800 mg once daily on Days 1--3, 24--26 and 34--36.

• DrugOdalasvir (ODV)

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

• DrugSimeprevir (SMV)

  Simeprevir 75 mg once daily on Days 4-13, 27--33 and 34--36.

Primary outcomes

1. Average Analyte Concentration at Steady State (Cavg,ss)

   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).

   Time frame: Up to Day 36

2. Maximum Observed Analyte Concentration (Cmax)

   The Cmax is the maximum observed analyte concentration.

   Time frame: Up to Day 36

3. Minimum Observed Analyte Concentration (Cmin)

   The Cmin is the minimum observed analyte concentration during dosing interval.

   Time frame: Up to Day 36

4. Trough Plasma Concentration (Ctrough)

   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.

   Time frame: Up to Day 36

5. Time to Reach Maximum Observed Analyte Concentration (Tmax)

   The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

   Time frame: Up to Day 36

6. Area Under the Analyte Concentration-Time Curve From Time 0 to 24 Hours (AUC24)

   The AUC24 is the area under the analyte concentration-time curve from time 0 to 24 hours.

   Time frame: Up to Day 36

7. Fluctuation Index (FI)

   Fluctuation Index is defined as percentage of fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100\*(\[Cmax-Cmin\]/Cavg).

   Time frame: Up to Day 36

8. Area Under the Analyte Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast)

   The (AUC \[0-last\]) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration.

   Time frame: Up to Day 36

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

   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: Up to Day 36

10. Elimination Rate Constant (Lambda[z])

    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.

    Time frame: Up to Day 36

11. Elimination Half-Life (t1/2)

    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).

    Time frame: Up to Day 36

Secondary outcomes

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)