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Trial record 24 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

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

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ClinicalTrials.gov Identifier: NCT02421211
Recruitment Status : Completed
First Posted : April 20, 2015
Results First Posted : January 5, 2017
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Sciences Ireland UC

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.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Drug: Simeprevir (SMV) Drug: Ledipasvir (LDV) Drug: Sofosbuvir (SOF) Phase 2

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: 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.
Actual Study Start Date : May 19, 2015
Actual Primary Completion Date : November 10, 2015
Actual Study Completion Date : January 27, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Panel 1
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)
Participants will receive 150 milligram (mg) of SMV (Treatment A) once daily in Panel 1 and Panel 2.

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

Drug: Sofosbuvir (SOF)
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.

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

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

Drug: Sofosbuvir (SOF)
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.




Primary Outcome Measures :
  1. Minimum Plasma Concentration (Cmin) of Simeprevir (SMV) [ 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.

  2. Maximum Plasma Concentration (Cmax) of Simeprevir [ 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.

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

  4. Minimum Plasma Concentration (Cmin) of Ledipasvir (LDV) [ 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.

  5. Maximum Plasma Concentration (Cmax) of Ledipasvir [ 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.

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


Secondary Outcome Measures :
  1. Trough Plasma Concentration (Ctrough) of Simeprevir [ 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.

  2. Time to Reach Maximum Plasma Concentration (Tmax) of Simeprevir [ 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.

  3. Average Plasma Concentration at Steady State (Cavg,ss) of Simeprevir [ 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).

  4. Fluctuation Index (FI) of Simeprevir [ 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).

  5. Trough Plasma Concentration (Ctrough) of Ledipasvir [ 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.

  6. Time to Reach Maximum Plasma Concentration (Tmax) of Ledipasvir [ 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.

  7. Average Plasma Concentration at Steady State (Cavg,ss) of Ledipasvir [ 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).

  8. Fluctuation Index (FI) of Ledipasvir [ 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).

  9. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ 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.

  10. Percentage of Participants With On-treatment Virologic Response [ 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.


  11. Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks After the Actual EOT (SVR4) and 12 Weeks After the Actual EOT (SVR12) [ 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.

  12. Percentage of Participants With On-treatment Failure [ 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).

  13. Percentage of Participants With Viral Relapse [ 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.

  14. 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 [ Time Frame: Up to end of follow-up phase (Week 12 of follow-up phase) in Panel 1 and Panel 2 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02421211


Locations
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Belgium
Antwerpen, Belgium
Brussel, Belgium
Gent, Belgium
Leuven, Belgium
Sponsors and Collaborators
Janssen Sciences Ireland UC
Investigators
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Study Director: Janssen Sciences Ireland UC Clinical Trial Janssen Sciences Ireland UC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen Sciences Ireland UC
ClinicalTrials.gov Identifier: NCT02421211     History of Changes
Other Study ID Numbers: CR106992
TMC435HPC2017 ( Other Identifier: Janssen Sciences Ireland UC )
2015-000459-25 ( EudraCT Number )
First Posted: April 20, 2015    Key Record Dates
Results First Posted: January 5, 2017
Last Update Posted: March 28, 2019
Last Verified: March 2019
Keywords provided by Janssen Sciences Ireland UC:
Hepatitis C, Chronic
Simeprevir
Ledipasvir
Sofosbuvir
Additional relevant MeSH terms:
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Virus Diseases
RNA Virus Infections
Ledipasvir
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
Flaviviridae Infections
Hepatitis, Chronic
Sofosbuvir
Simeprevir
Antiviral Agents
Anti-Infective Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action