NCT02421211

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
41

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started May 2015

Shorter than P25 for phase_2

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 15, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 20, 2015

Completed
29 days until next milestone

Study Start

First participant enrolled

May 19, 2015

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 10, 2015

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2016

Completed
11 months until next milestone

Results Posted

Study results publicly available

January 5, 2017

Completed
Last Updated

March 28, 2019

Status Verified

March 1, 2019

Enrollment Period

6 months

First QC Date

April 15, 2015

Results QC Date

November 7, 2016

Last Update Submit

March 27, 2019

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C, ChronicSimeprevirLedipasvirSofosbuvir

Outcome Measures

Primary Outcomes (6)

  • Minimum Plasma Concentration (Cmin) of Simeprevir (SMV)

    The Cmin is the minimum observed plasma concentration.

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

  • Maximum Plasma Concentration (Cmax) of Simeprevir

    The Cmax is the maximum observed plasma concentration.

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Simeprevir

    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.

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

  • Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV)

    The Cmin is the minimum observed plasma concentration.

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

  • Maximum Plasma Concentration (Cmax) of Ledipasvir

    The Cmax is the maximum observed plasma concentration.

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Ledipasvir

    AUCtau is defined as area under the analyte concentration versus time curve during dosing interval tau, calculated by linear-linear trapezoidal summation.

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

Secondary Outcomes (14)

  • Trough Plasma Concentration (Ctrough) of Simeprevir

    Pre-dose on Day 14 and Day 28

  • Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

  • Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir

    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 (FI) of Simeprevir

    Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 18, and 24 hours post-dose on Day 14 and Day 28

  • Trough Plasma Concentration (Ctrough) of Ledipasvir

    Pre-dose on Day 14 and Day 28

  • +9 more secondary outcomes

Study Arms (2)

Panel 1

EXPERIMENTAL

Participants will receive Simeprevir (SMV) 150 milligram (mg) capsule (Treatment A) along with Sofosbuvir (SOF) 400 mg tablet, orally, once daily (Treatment C) from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with fixed dose combination (FDC) tablet of 90 mg Ledipasvir (LDV)/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 70.

Drug: Simeprevir (SMV)Drug: Ledipasvir (LDV)Drug: Sofosbuvir (SOF)

Panel 2

EXPERIMENTAL

Participants will receive FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 1 until Day 14 followed by SMV 150 mg capsule (Treatment A) along with FDC tablet of 90 mg LDV/400 mg SOF (Treatment B), orally, once daily from Day 15 until Day 56.

Drug: Simeprevir (SMV)Drug: Ledipasvir (LDV)Drug: Sofosbuvir (SOF)

Interventions

Simeprevir (SMV)DRUG

Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.

Panel 1Panel 2
Ledipasvir (LDV)DRUG

Participants will receive 90 mg of LDV once daily as FDC tablet with SOF (Treatment B) in Panel 1 and Panel 2.

Panel 1Panel 2
Sofosbuvir (SOF)DRUG

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.

Panel 1Panel 2

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Unknown Facility

Antwerp, Belgium

Location

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Ghent, Belgium

Location

Unknown Facility

Leuven, Belgium

Location

Related Publications (1)

  • Bourgeois S, Horsmans Y, Nevens F, van Vlierberghe H, Moreno C, Beumont M, Vijgen L, van Eygen V, Luo D, Hillewaert V, Van Remoortere P, van de Logt J, Ouwerkerk-Mahadevan S. Pharmacokinetic Interactions between Simeprevir and Ledipasvir in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients without Cirrhosis Treated with a Simeprevir-Sofosbuvir-Ledipasvir Regimen. Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01217-17. doi: 10.1128/AAC.01217-17. Print 2017 Dec.

    PMID: 28971875DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

SimeprevirledipasvirSofosbuvir

Condition Hierarchy (Ancestors)

Hepatitis CBlood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

SulfonamidesSulfonesSulfur CompoundsOrganic ChemicalsHeterocyclic Compounds, 3-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsUridine MonophosphateUracil NucleotidesPyrimidine NucleotidesPyrimidinesHeterocyclic Compounds, 1-RingNucleotidesNucleic Acids, Nucleotides, and NucleosidesRibonucleotides

Results Point of Contact

Title
Trial Physician, Clinical Development
Organization
Janssen Research & Development
ClinicalTrialDisclosure@its.jnj.com

Study Officials

  • Janssen Sciences Ireland UC Clinical Trial

    Janssen Sciences Ireland UC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 15, 2015

First Posted

April 20, 2015

Study Start

May 19, 2015

Primary Completion

November 10, 2015

Study Completion

January 27, 2016

Last Updated

March 28, 2019

Results First Posted

January 5, 2017

Record last verified: 2019-03

Locations

BE(4)