Simeprevir (SMV)
DrugParticipants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.
NCT Number: NCT02421211
The purpose of this study is to evaluate the pharmacokinetic interactions between simeprevir and ledipasvir in a treatment regimen consisting of simeprevir (SMV), sofosbuvir (SOF), and ledipasvir (LDV) in treatment-naive participants with chronic hepatitis C virus (HCV) genotype 1 infection.
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Notify Me18 year–70 year
All sexes
Interventional
Phase 2
Antwerp, Belgium
This is an open-label (all people know the identity of the intervention), 2-panel, Phase 2, randomized (study medication assigned to participants by chance) study. The study will consist of 3 study phases: Screening Phase (5 weeks), an Open-label Treatment Phase (70 days for Panel 1 and 56 days for Panel 2), a Post-treatment Follow-up Phase (12 weeks after the actual end of treatment). Participants will receive a combination of the following treatments: Treatment A: SMV 150 milligram (mg) once daily; Treatment B: LDV 90 mg along with SOF 400 mg once daily; Treatment C: SOF 400 mg once daily. Participants will be randomly assigned to Panel 1 (Treatment AC followed by Treatment AB) and Panel 2 (Treatment B followed by Treatment AB). The total study duration will be approximately 27 weeks for participants in Panel 1 and 25 weeks for participants in Panel 2. Participants will be primarily accessed for pharmacokinetic parameters. Participants' safety will be monitored throughout the study.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.
Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2.
Participants will receive 400 mg of SOF alone (Treatment C) in Panel 1 and as FDC tablet with LDV (Treatment B) once daily in Panel 2.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmin is the minimum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmax is the maximum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The AUCtau is the measure of the plasma drug concentration from time zero to end of dosing interval. It is used to characterize drug absorption.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmin is the minimum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Cmax is the maximum observed plasma concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.
Time frame: Pre-dose on Day 14 and Day 28
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: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
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: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).
Time frame: Pre-dose on Day 14 and Day 28
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: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
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: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28
Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).
Time frame: Up to 10 Weeks for Panel 1 and 8 Weeks for Panel 2
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Week 1, up to EOT (Week 10 in Panel 1 and Week 8 in Panel 2)
On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold.
The following thresholds were considered at any time point: less than (<) lower limit of quantification (LLOQ) undetectable, <LLOQ detectable and <LLOQ undetectable/detectable.
Time frame: 4 weeks after EOT (Week 4 of follow-up phase in Panel 1 and Panel 2) and 12 weeks after EOT (Week 12 of follow-up phase in Panel 1 and Panel 2)
SVR4 or SVR12 is defined as sustained virologic response 4 or 12 weeks after the actual EOT the participant has HCV RNA <LLOQ detectable or undetectable.
Time frame: Day 70 in Panel 1 and Day 56 in Panel 2
On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been <LLOQ while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to AEs, withdrawal of consent).
Time frame: Up to Week 12 follow-up phase after EOT
Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up.
Time frame: Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2
Janssen Sciences Ireland UC
Industry
A Phase 2, 2-panel, Open-label Randomized Study in Hepatitis C Virus Infected Subjects to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir and Ledipasvir in Treatment-naive Participants.
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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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