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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02824315
• Other study ID #: CR108179
• Secondary ID: 64294178HPC10062
• Status: Completed
• Phase: Phase 1
• First received: June 7, 2016
• Last updated: November 30, 2016
• Start date: May 2016
• Est. completion date: October 2016

Study information

• Verified date: November 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Great Britain: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 55 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• AL-335
AL--335 800 mg once daily on Days 1--3, 24--26 and 34--36.
• Odalasvir (ODV)
ODV 150 mg on Day 14 and 50 mg once daily on Days 15--23, 24--26, 27--33 and 34--36.
• Simeprevir (SMV)
Simeprevir 75 mg once daily on Days 4-13, 27--33 and 34--36.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Up to Day 36	No
Primary	Maximum Observed Analyte Concentration (Cmax)	The Cmax is the maximum observed analyte concentration.	Up to Day 36	No
Primary	Minimum Observed Analyte Concentration (Cmin)	The Cmin is the minimum observed analyte concentration during dosing interval.	Up to Day 36	No
Primary	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.	Up to Day 36	No
Primary	Time to Reach Maximum Observed Analyte Concentration (Tmax)	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Up to Day 36	No
Primary	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.	Up to Day 36	No
Primary	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).	Up to Day 36	No
Primary	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.	Up to Day 36	No
Primary	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.	Up to Day 36	No
Primary	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.	Up to Day 36	No
Primary	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).	Up to Day 36	No
Secondary	Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability		Up to Follow-up (170 to 175 days after last study drug intake)	Yes