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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-002232-85 | EudraCT Number |
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This is a three-year (except for participants with chronic kidney disease [CKD] or cirrhosis) multicenter study to follow participants who received at least one dose of grazoprevir (MK-5172) in a previous study to determine whether they remain hepatitis C virus (HCV)-Ribonucleic acid (RNA) negative over time, and to determine if they have developed antiviral resistance. The study will also evaluate long-term adverse events in this population. Participants from MK-5172-052 (NCT02092350) with CKD or cirrhosis will be followed for five years.
As of Amendment 03, the study design is revised such that continued enrollment will only be for participants who failed prior therapy with a grazoprevir regimen. Participants with CKD enrolled from MK-5172-052 (NCT02092350) will continue enrollment regardless of prior treatment-response and remain in this study for five years, while participants enrolled from all other studies with HCV RNA less than the lower limit of quantitation (LLOQ) will be discontinued and end their participation after the next scheduled visit. In addition, participants who receive other HCV treatments concurrent with this follow-up study or received other HCV treatments prior to this study will be discontinued and their data excluded from analysis.
As of Amendment 04, the protocol has been updated to include enrollment of pediatric participants from protocol MK-5172-079 (NCT03379506). Enrollment is limited to participants who experienced virologic failure associated with 1 or more treatment-emergent resistant associated substitutions (RASs) present at 12 weeks after receiving grazoprevir treatment in prior treatment study MK-5172-079 (NCT03379506).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Grazoprevir | Participants who previously received grazoprevir as study treatment on a prior study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Grazoprevir | Drug | Participants previously received study treatment with grazoprevir at the dose and frequency specified in the study protocol. Grazoprevir was not administered to participants in the course of this follow-up study. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Viral Relapse | Viral relapse is defined as any participant who has confirmed HCV Ribonucleic acid (RNA) ≥ Lower limit of quantification (LLoQ) of 15 IU/mL and had achieved sustained virologic response (SVR) in the follow up in the prior treatment study. Time to relapse is defined as the time from last dose of study therapy taken in the prior treatment study until the date where HCV RNA is ≥LLoQ. | Up to ~60 months after enrollment in this study |
| Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections | In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time. | Up to ~60 months after enrollment in this study |
| Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections | In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time. | Up to ~60 months after enrollment in this study |
| Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections | In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time. | Up to ~60 months after enrollment in this study |
| Number of Participants Who Experienced a Drug-Related Adverse Event (AE) During the Long-Term Follow-Up | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The study investigator determined whether the adverse event was drug-related. |
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Inclusion Criteria:
Exclusion Criteria:
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Adult and pediatric participants previously treated with a grazoprevir-containing regimen while enrolled in a Merck study. All participants enrolled having failed therapy from prior studies (except MK-5172-052 [NCT02092350]) will be followed for 3 years in the current follow-up study, and all participants enrolled from MK-5172-052 (irrespective of prior response) will be followed for 5 years in the current follow-up study.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30038064 | Background | Lahser F, Galloway A, Hwang P, Palcza J, Brunhofer J, Wahl J, Robertson M, Barr E, Black T, Asante-Appiah E, Haber B. Interim analysis of a 3-year follow-up study of NS5A and NS3 resistance-associated substitutions after treatment with grazoprevir-containing regimens in participants with chronic HCV infection. Antivir Ther. 2018;23(7):593-603. doi: 10.3851/IMP3253. Epub 2018 Jul 24. |
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Of the 2438 participants, three participants were excluded from all analyses. Two participants enrolled in error failed to receive at least 1 dose of Grazoprevir (GZR) in a prior study (each received a comparator regimen in a prior base study) and 1 participant had insufficient long-term follow-up data (participant withdrew consent on Day 27).
A total of 2438 adult Hepatitis C Virus (HCV)-infected participants who were previously treated in 18 prior clinical trials, enrolled in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Grazoprevir (GZR) 100 mg + Elbasvir (EBR) 50 mg +/- Ribavirin (RBV) | Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study. |
| FG001 | Other GZR Regimen |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 13, 2018 |
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Blood samples will be collected and retained for purposes of Deoxyribonucleic acid (DNA) testing and plasma will be retained for future biomedical research.
| Up to ~ 60 months after enrollment in this study |
| Number of Participants Who Experienced a Drug-Related Serious Adverse Event (SAE) During the Long-Term Follow-Up | A serious adverse event (SAE) is any adverse experience occurring at any dose that either results in death, is life threatening, results in a persistent or significant disability/incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose (whether accidental or intentional), or other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse experience when, based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed previously. The study investigator determined whether the adverse event was drug-related. | Up to ~60 months after enrollment in this study |
| Number of Participants Who Experienced an Event of Clinical Interest (ECI) During the Long-Term Follow-Up | An ECI includes spontaneous bacterial peritonitis, variceal bleeding, ascites, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, liver transplant, cardiovascular disease limited to angina and myocardial infarction, neurologic disorders limited to transient ischemic attack (TIA) or stroke, graft rejection in participants who have undergone liver or kidney transplant, or one of the following in participants from the MK-5172-052 (NCT02092350) base study: kidney transplant, decreased estimated glomerular filtration rate (eGFR), new onset diabetes, cryoglobulinemia, or post transplantation glomerulonephritis. | Up to ~60 months after enrollment in this study |
Participants previously received at least one dose of GZR in a prior study
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | GZR 100 mg + EBR 50 mg +/- RBV | Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study. |
| BG001 | Other GZR Regimen | Participants previously received at least one dose of GZR in a prior study |
| 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 | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| 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 | Time to Viral Relapse | Viral relapse is defined as any participant who has confirmed HCV Ribonucleic acid (RNA) ≥ Lower limit of quantification (LLoQ) of 15 IU/mL and had achieved sustained virologic response (SVR) in the follow up in the prior treatment study. Time to relapse is defined as the time from last dose of study therapy taken in the prior treatment study until the date where HCV RNA is ≥LLoQ. | All participants who achieved SVR during the follow-up period of the prior treatment study and did not start any new HCV therapy between the end of the prior treatment study and entry in this study | Posted | Median | Inter-Quartile Range | Months | Up to ~60 months after enrollment in this study |
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|
| ||||||||||||||||||||||||||||
| Primary | Persistence of Treatment-Emergent Nonstructural Protein (NS)3 and NS5A Resistance-associated Substitutions (RASs) in Participants With HCV Genotype (GT) 1a Infections | In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time. | Participants met the criteria of virologic failure either in the prior base study or had HCV RNA Target detected, quantifiable [TD(q)] at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included. | Posted | Count of Participants | Participants | Up to ~60 months after enrollment in this study |
| |||||||||||||||||||||||||||||||
| Primary | Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With HCV Genotype 1b Infections | In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time. | Participants met the criteria of virologic failure either in the prior base study or had HCV RNA TD(q) at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included. | Posted | Count of Participants | Participants | Up to ~60 months after enrollment in this study |
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| Primary | Persistence of Treatment-Emergent NS3 and NS5A RASs in Participants With Genotype 4 Infections | In adult participants with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis was performed to evaluate the presence of RASs and the persistence of RASs over time. | Participants met the criteria of virologic failure either in the prior base study or had HCV RNA TD(q) at entry in current study. Participants did not receive new HCV therapy between the end of the prior base study and entry into this study. Only HCV genotype infections that had adequate reference information were included. | Posted | Count of Participants | Participants | Up to ~60 months after enrollment in this study |
| |||||||||||||||||||||||||||||||
| Primary | Number of Participants Who Experienced a Drug-Related Adverse Event (AE) During the Long-Term Follow-Up | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The study investigator determined whether the adverse event was drug-related. | All participants treated with GZR in a prior study. Three participants were excluded from analysis; two participants enrolled in error failed to receive at least one dose of GZR in a prior study (each received a comparator regimen in a prior base study) and one participant had insufficient long-term follow-up data (participant withdrew consent on Day 27). | Posted | Count of Participants | Participants | Up to ~ 60 months after enrollment in this study |
|
| ||||||||||||||||||||||||||||||
| Primary | Number of Participants Who Experienced a Drug-Related Serious Adverse Event (SAE) During the Long-Term Follow-Up | A serious adverse event (SAE) is any adverse experience occurring at any dose that either results in death, is life threatening, results in a persistent or significant disability/incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose (whether accidental or intentional), or other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse experience when, based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed previously. The study investigator determined whether the adverse event was drug-related. | All participants treated with GZR in a prior study. Three participants were excluded from analysis; two participants enrolled in error failed to receive at least one dose of GZR in a prior study (each received a comparator regimen in a prior base study) and one participant had insufficient long-term follow-up data (participant withdrew consent on Day 27). | Posted | Count of Participants | Participants | Up to ~60 months after enrollment in this study |
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| Primary | Number of Participants Who Experienced an Event of Clinical Interest (ECI) During the Long-Term Follow-Up | An ECI includes spontaneous bacterial peritonitis, variceal bleeding, ascites, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, liver transplant, cardiovascular disease limited to angina and myocardial infarction, neurologic disorders limited to transient ischemic attack (TIA) or stroke, graft rejection in participants who have undergone liver or kidney transplant, or one of the following in participants from the MK-5172-052 (NCT02092350) base study: kidney transplant, decreased estimated glomerular filtration rate (eGFR), new onset diabetes, cryoglobulinemia, or post transplantation glomerulonephritis. | All participants treated with GZR in a prior study. Three participants were excluded from analysis; two participants enrolled in error failed to receive at least one dose of GZR in a prior study (each received a comparator regimen in a prior base study) and one participant had insufficient long-term follow-up data (participant withdrew consent on Day 27). | Posted | Count of Participants | Participants | Up to ~60 months after enrollment in this study |
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From first visit in follow-up (Screening/Baseline) up to ~60 months after enrollment in this study
The all-cause mortality population includes all enrolled participants (N=2438). The serious adverse events and other adverse events population excludes three enrolled participants- two enrolled in error who received a comparator regimen in a prior base study and one participant had insufficient long-term follow up data (participant withdrew consent on day 27).
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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 | GZR 100 mg + EBR 50 mg +/- RBV | Participants previously received GZR 100mg +EBR 50mg with or without RBV in a prior study. | 44 | 1,909 | 100 | 1,909 | 0 | 1,909 |
| EG001 | Other GZR Regimen | Participants previously received at least one dose of GZR in a prior study | 3 | 527 | 4 | 526 | 0 | 526 |
| EG002 | Non-GZR Regimen | Participants received a non-GZR regimen in a prior study | 0 | 2 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Angina unstable | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Myocardial ischaemia | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Pulseless electrical activity | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Death | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Sudden death | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Chronic hepatic failure | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
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| Hepatic cirrhosis | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
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| Kidney transplant rejection | Immune system disorders | MedDRA 24.0 | Systematic Assessment |
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| Device related sepsis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Peritonitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
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| Overdose | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
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| Transplant dysfunction | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
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| Glomerular filtration rate decreased | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Failure to thrive | Metabolism and nutrition disorders | MedDRA 24.0 | Systematic Assessment |
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| Adenocarcinoma pancreas | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.0 | Systematic Assessment |
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| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.0 | Systematic Assessment |
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| Hepatocellular carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.0 | Systematic Assessment |
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| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.0 | Systematic Assessment |
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| Non-small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.0 | Systematic Assessment |
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| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 24.0 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Embolic stroke | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Hepatic encephalopathy | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Ischaemic cerebral infarction | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Ischaemic stroke | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Optic neuritis | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Transient ischaemic attack | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 24.0 | Systematic Assessment |
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| Chronic kidney disease | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
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| End stage renal disease | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
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| Glomerulonephritis chronic | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
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| Renal impairment | Renal and urinary disorders | MedDRA 24.0 | Systematic Assessment |
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| Asphyxia | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Respiratory arrest | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Mar 7, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| 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 |
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| ID | Term |
|---|---|
| C578009 | grazoprevir |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| OG003 | GZR + Pegylated Interferon/Ribavirin (PR): NS3 RASs | Participants previously received GZR and PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs |
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| OG003 | GZR + RBV or PR: NS3 RASs | Participants previously received GZR and RBV or PR for 12 weeks in a prior study and had treatment-emergent NS3 RASs |
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Participants previously received at least one dose of GZR in a prior study |
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