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| ID | Type | Description | Link |
|---|---|---|---|
| TMC435HPC3017 | Other Identifier | Janssen Infectious Diseases BVBA |
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The purpose of the study is to evaluate the efficacy and safety of a treatment regimen of 12 weeks or 8 weeks of simeprevir in combination with sofosbuvir in chronic hepatitis C virus (HCV) genotype 1 infected men and women without cirrhosis who are HCV treatment-naïve or treatment-experienced.
This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), multicenter study. The study will consist of a screening phase up to 6 weeks, open-label treatment phase of 8 weeks or 12 weeks, and post-treatment follow up phase up to 24 weeks after end of treatment. Approximately 300 participants will be randomly allocated in a 1:1 ratio to receive 150 mg simeprevir in combination with 400 mg sofosbuvir once daily either for 12 weeks (Arm 1) or 8 weeks (Arm 2). Safety evaluations will include assessment of adverse events, clinical laboratory tests, vital signs, and physical examination. The maximum study duration for each participant will be approximately 42 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 (Simeprevir/Sofosbuvir) | Experimental | 150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks. |
|
| Arm 2 (Simeprevir/Sofosbuvir) | Experimental | 150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simeprevir | Drug | 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | Participants considered to have achieved SVR12, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the actual end of study drug treatment. | 12 weeks after the end of treatment (EOT) (Week 20 or Week 24) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4) | Participants considered to have achieved SVR4, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 4 weeks after the actual end of study drug treatment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Infectious Diseases BVBA Clinical Trial | Janssen Infectious Diseases BVBA | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dothan | Alabama | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26799692 | Derived | Kwo P, Gitlin N, Nahass R, Bernstein D, Etzkorn K, Rojter S, Schiff E, Davis M, Ruane P, Younes Z, Kalmeijer R, Sinha R, Peeters M, Lenz O, Fevery B, De La Rosa G, Scott J, Witek J. Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. Hepatology. 2016 Aug;64(2):370-80. doi: 10.1002/hep.28467. Epub 2016 Mar 22. |
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A total of 310 participants were randomly allocated to the 2 treatment arms. All participants received at least 1 dose of study drug and were included in intent to treat (ITT) analysis set.
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| ID | Title | Description |
|---|---|---|
| FG000 | Simeprevir and Sofosbuvir for 8 Weeks | Participants received 1 capsule of 150 milligram (mg) simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 8 weeks. |
| FG001 | Simeprevir and Sofosbuvir for 12 Weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Simeprevir | Drug | 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 8 weeks in Arm 2 |
|
| Sofosbuvir | Drug | 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1. |
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| Sofosbuvir | Drug | 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2. |
|
| 4 weeks after the end of treatment (EOT) (Week 12 or Week 16) |
| Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | Participants considered to have achieved SVR24, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 24 weeks after the Actual end of study drug treatment. | 24 weeks after the end of treatment (EOT) (Week 32 or Week 36) |
| Percentage of Participants Achieving a On-treatment Virologic Response | Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold. \ | Day 14, Day 28, End of treatment (Week 8 or Week 12) |
| Percentage of Participants With Viral Breakthrough | Percentage of participants with greater than 1 log10 IU/mL increase in plasma Hepatitis C virus ribonucleic acid level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been less than 25 IU/mL. | Up to Week 24 |
| Percentage of Participants With Viral Relapse | Percentage of participants who did not achieve sustained virologic response 12, have less than 25 IU/mL undetectable plasma HCV RNA at end of treatment, and greater than or equal to 25 IU/mL plasma HCV RNA during the follow-up phase. | Up to Week 24 |
| Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | HCVSIQv4 OBSS was a self-administered questionnaire that contained 33 items: 29 questions developed to assess severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. A symptom severity score (the mean of responses to the 29 symptom items); each symptom score was transformed to have a range from 0 to 100 (most severe). Higher HCV SIQv4 scores indicates worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
| Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | The FSS was a self-administered questionnaire with 9 items developed to assess disabling fatigue that has been used extensively in studies of chronic HCV infection. Item responses were measured on a 7point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items were averaged to produce a total score; a lower total score indicates less severe fatigue. FSS scores have a range from 1 to 7 where higher scores indicate more severe fatigue. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
| Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | The CES-D scale assesses how often during the past week participants experienced 20 symptoms commonly associated with major depression. CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5-7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores greater than or equal to 23 indicate probable major depressive illness. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
| Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
| Bakersfield |
| California |
| United States |
| Chula Vista | California | United States |
| Los Angeles | California | United States |
| San Diego | California | United States |
| Englewood | Colorado | United States |
| Bradenton | Florida | United States |
| Jacksonville | Florida | United States |
| Lauderdale Lakes | Florida | United States |
| Maitland | Florida | United States |
| Miami | Florida | United States |
| Orlando | Florida | United States |
| Wellington | Florida | United States |
| Zephyrhills | Florida | United States |
| Atlanta | Georgia | United States |
| Columbus | Georgia | United States |
| Marietta | Georgia | United States |
| Indianapolis | Indiana | United States |
| Jackson | Mississippi | United States |
| Kansas City | Missouri | United States |
| Hillsborough | New Jersey | United States |
| Vineland | New Jersey | United States |
| Manhasset | New York | United States |
| New York | New York | United States |
| Asheville | North Carolina | United States |
| Winston-Salem | North Carolina | United States |
| Pittsburgh | Pennsylvania | United States |
| East Greenwich | Rhode Island | United States |
| Providence | Rhode Island | United States |
| Greer | South Carolina | United States |
| Germantown | Tennessee | United States |
| Knoxville | Tennessee | United States |
| Nashville | Tennessee | United States |
| Arlington | Texas | United States |
| Austin | Texas | United States |
| San Antonio | Texas | United States |
| Falls Church | Virginia | United States |
| Norfolk | Virginia | United States |
| Vancouver | British Columbia | Canada |
| Montreal | Quebec | Canada |
Participants received 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Simeprevir and Sofosbuvir for 8 Weeks | Participants received 1 capsule of 150 milligram (mg) simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 8 weeks. |
| BG001 | Simeprevir and Sofosbuvir for 12 Weeks | Participants received 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | Participants considered to have achieved SVR12, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the actual end of study drug treatment. | Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of participants | 12 weeks after the end of treatment (EOT) (Week 20 or Week 24) |
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| Secondary | Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4) | Participants considered to have achieved SVR4, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 4 weeks after the actual end of study drug treatment. | Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of Participants | 4 weeks after the end of treatment (EOT) (Week 12 or Week 16) |
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| Secondary | Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | Participants considered to have achieved SVR24, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 24 weeks after the Actual end of study drug treatment. | Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of participants | 24 weeks after the end of treatment (EOT) (Week 32 or Week 36) |
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| Secondary | Percentage of Participants Achieving a On-treatment Virologic Response | Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold. \ | The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, 'n' specifies those participants who were evaluated for this outcome measure at given time point. | Posted | Number | Percentage of participants | Day 14, Day 28, End of treatment (Week 8 or Week 12) |
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| Secondary | Percentage of Participants With Viral Breakthrough | Percentage of participants with greater than 1 log10 IU/mL increase in plasma Hepatitis C virus ribonucleic acid level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been less than 25 IU/mL. | The ITT population included all the randomized participants who took at least 1 dose of study drug. | Posted | Number | Percentage of participants | Up to Week 24 |
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| Secondary | Percentage of Participants With Viral Relapse | Percentage of participants who did not achieve sustained virologic response 12, have less than 25 IU/mL undetectable plasma HCV RNA at end of treatment, and greater than or equal to 25 IU/mL plasma HCV RNA during the follow-up phase. | The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure. | Posted | Number | Percentage of participants | Up to Week 24 |
|
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| Secondary | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | HCVSIQv4 OBSS was a self-administered questionnaire that contained 33 items: 29 questions developed to assess severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. A symptom severity score (the mean of responses to the 29 symptom items); each symptom score was transformed to have a range from 0 to 100 (most severe). Higher HCV SIQv4 scores indicates worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively. | The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
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| Secondary | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | The FSS was a self-administered questionnaire with 9 items developed to assess disabling fatigue that has been used extensively in studies of chronic HCV infection. Item responses were measured on a 7point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items were averaged to produce a total score; a lower total score indicates less severe fatigue. FSS scores have a range from 1 to 7 where higher scores indicate more severe fatigue. | The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
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| Secondary | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | The CES-D scale assesses how often during the past week participants experienced 20 symptoms commonly associated with major depression. CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5-7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores greater than or equal to 23 indicate probable major depressive illness. | The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening. | The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point. | Posted | Mean | Standard Error | units on a scale | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 |
|
Baseline to End of Treatment (week 8 or week 12)
The total number of adverse events listed in the "Other (nonSerious) Adverse Event" table are based on at least 5 percent of participants experiencing the adverse event in any treatment arm
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Simeprevir and Sofosbuvir for 8 Weeks | Participants received 1 capsule of 150 milligram (mg) simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 8 weeks. | 3 | 155 | 68 | 155 | ||
| EG001 | Simeprevir and Sofosbuvir for 12 Weeks | Participants received 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks. | 2 | 155 | 65 | 155 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Post-traumatic neck syndrome | Injury, poisoning and procedural complications | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Mania | Psychiatric disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 17.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 17.1 | Non-systematic Assessment |
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A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Associate Director Clinical Research | Janssen Infectious Diseases BVBA | ClinicalTrialDisclosure@its.jnj.com |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000069616 | Simeprevir |
| D000069474 | Sofosbuvir |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D014542 | Uridine Monophosphate |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |
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| Male |
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Participants received 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks.
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| Units | Counts |
|---|---|
| Participants |
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