Phase 2
Completed N=40
A Study to Investigate the Pharmacokinetic Interactions Between Simeprevir and Ledipasvir in a Treatment Regimen Consisting of Simeprevir, Sofosbuvir, and Ledipasvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection
Hepatitis C, Chronic
Source: ClinicalTrials.gov NCT02421211 ↗
Enrolled (actual)
40
Serious AEs
5.0%
Results posted
Jan 2017
Primary outcomePrimary: Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) — 2411; 6701 nanogram per Milliliters (ng/mL)
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) |
2411; 6701 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Simeprevir |
6767; 13691 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir |
100492; 243564 | — |
| PRIMARY Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV) |
319; 557 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Ledipasvir |
556; 930 | — |
| PRIMARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir |
9868; 17435 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Simeprevir |
3059; 8453 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir |
6.00; 6.00 | — |
| SECONDARY Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir |
4196; 10139 | — |
| SECONDARY Fluctuation Index (FI) of Simeprevir |
144; 84.4 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Ledipasvir |
376; 659 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir |
4.07; 6.00 | — |
| SECONDARY Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir |
411; 725 | — |
| SECONDARY Fluctuation Index (FI) of Ledipasvir |
60.6; 51.2 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
17; 15; 2; 0 | — |
| SECONDARY Percentage of Participants With On-treatment Virologic Response |
65.0; 60.0; 35.0; 40.0; 15.0; 35.0 | — |
| SECONDARY Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) |
100; 100; 100; 100 | — |
| SECONDARY Percentage of Participants With On-treatment Failure |
0; 0 | — |
| SECONDARY Percentage of Participants With Viral Relapse |
0; 0 | — |
| SECONDARY Number of Participants Not Achieving Sustained Virologic Response (SVR) Showing Emerging Mutation in HCV Nonstructural Protein 3/4A (NS3/4A), Nonstructural Protein 5A (NS5A), and Nonstructural Protein 5B (NS5B) Sequence |
— | — |
Eligibility Criteria
Inclusion Criteria
- Participants with Body Mass Index (weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 35.0 kilogram per square meter kg/m^2, extremes included
- Participants must be treatment-naive (that is, have not received prior treatment with any approved or investigational drug)
- Participants with HCV ribonucleic acid (RNA) plasma levels greater than (>) 10,000 international unit per milliliter (IU/ml) and lower than 6,000,000 international unit per milliliter (IU/ml) at screening
- Participants with absence of cirrhosis confirmed by FibroTest/Fibrosure score less or equal to 0.75 and an aspartate aminotransferase to platelet ration index less or equal to 2 or a Fibroscan less or equal to 14.6 kilopascale (kPA), performed within 6 months prior or during the screening period
- Participants with documented chronic HCV infection: diagnosis of HCV infection >6 months prior to screening, either by detectable HCV RNA, an HCV positive antibody test or presence of histological changes consistent with chronic hepatitis in a liver biopsy
Exclusion Criteria
- Participant has infection/co-infection with HCV of a genotype other than genotype 1, human immunodeficiency virus (HIV) type 1 or 2
- Participant has any evidence of liver disease of non-HCV etiology. This includes, but is not limited to acute hepatitis A, active hepatitis B, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HC liver disease considered clinically significant by the investigator
- Participant with significant co-morbidities, conditions or clinical significant findings during screening assessments that in the opinion of the investigator could compromise the participants' safety or could interfere with the Participant participating in and completing the study
- Participant received an organ transplant (other than cornea or hair transplant or skin graft)
- Participants have key protocol defined laboratory abnormalities
Data sourced from ClinicalTrials.gov (NCT02421211). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.