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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001687-18 | EudraCT Number |
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This study will evaluate safety, pharmacokinetics (PK), and the ability of MK-1075 to suppress viral load (VL) in HCV-infected participants during 7 days of once daily dose administration. The primary hypothesis is at a once-daily dose that is sufficiently safe and well tolerated in HCV-infected participants, the mean maximum HCV RNA (log10 IU/mL) reduction is at least 3 log10 IU/mL as compared to baseline following multiple dose oral administration of MK-1075 in HCV genotype 1 (GT1) and genotype 3 (GT3) infected participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GT1: 200 mg MK-1075 | Experimental | Fasted GT1 participants are administered 200 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
|
| GT1: 400 mg MK-1075 | Experimental | Fasted GT1 participants are administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
|
| GT1: 800 mg MK-1075 | Experimental | Fasted GT1 participants are administered 800 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
|
| GT3: 200 mg MK-1075 | Experimental | Fasted GT3 participants are administered 200 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
|
| GT3: 400 mg MK-1075 | Experimental | Fasted GT3 participants are administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
|
| GT3: 800 mg MK-1075 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 200 mg MK-1075 | Drug | Two 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Up to Day 42 |
| Number of Participants Who Discontinued Treatment Due to an AE | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Up to Day 7 |
| Change From Baseline in Maximum log10 HCV RNA Following Multiple Dose Oral Administration of MK-1075 | Blood was collected on Days 1, 3, 4, 5, 6, 7, 21, 28 and 42, where baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing. Change from baseline in log10 HCV RNA levels, was determined, and the maximum reduction in HCV RNA was analyzed by an ANOVA model with a fixed effect for treatment. The primary hypothesis is, with a posterior probability larger than 70%, there is at least a 3 log10 reduction from baseline in HCV RNA. | Day 1 (pre-dose, 2, 4, 8, 12, and 24 hours postdose); Days 3, 4, 5, 6 (pre-dose); Day 7 (predose, 4, 12, 24, 48, 72, 96, 120, and 192 hours postdose); Days 21, 28 and 42 |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC 0-24hr of MK-1075 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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GT1 and GT3 participants planned to receive 200 mg MK-1075 were not treated based on available data from previous studies.
Males or females of non-child bearing potential with verified Genotype 1 (GT1) or Genotype 3 (GT3) Hepatitis C Virus (HCV) infection, between the ages of 18 and 65 years (inclusive) were enrolled in this trial.
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| ID | Title | Description |
|---|---|---|
| FG000 | GT1 400 mg MK-1075 | Fasted GT1 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| FG001 | GT1 MK-1075 600 mg | Fasted GT1 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| FG002 | GT3 400 mg MK-1075 | Fasted GT3 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| FG003 | GT3 600 mg MK-1075 | Fasted GT3 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | GT1 400 mg MK-1075 | Fasted GT1 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| BG001 | GT1 MK-1075 600 mg | Fasted GT1 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants Who Experienced an Adverse Event (AE) | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Participants who received at least one dose of the investigational drug. | Posted | Count of Participants | Participants | Up to Day 42 |
|
Pre-treatment: 28 days before treatment up to Treatment; Treatment: Day 1 up to Day 7; Post-Treatment: Day 8 up to day 42
Participants who received at least one dose of the investigational drug. Adverse events are also reported for GT1 and GT3 arms during Pre-treatment and Post-study periods.
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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 | GT1 Pre-treatment | GT1 participants were enrolled for 4 weeks prior to randomization and treatment. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| White blood cells urine positive | Investigations | MedDRA 18.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| Experimental |
Fasted GT3 participants are administered 800 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
|
| 400 mg MK-1075 | Drug | Four 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days |
|
| 800 mg MK-1075 | Drug | Eight 100 mg tablets of MK-1075 administered orally, once daily for 7 consecutive days |
|
| Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose |
| AUC 0-24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC 0-24hr of the MK-1075 metabolite M1 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. | Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose |
| Area Under the Plasma Concentration Time Curve From Time 0 to Last (AUC 0-last) of MK-1075 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 120 hours post-dose in order to determine the plasma AUC 0-last of MK-1075 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. | Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose |
| AUC 0-last of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 120 hours post-dose in order to determine the plasma AUC 0-last of M1 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. | Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose |
| Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected at 24 hours post-dose in order to determine the plasma C24hr of MK- 1075 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). | Day 7 at 24 hours postdose |
| C24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected at 24 hours post-dose in order to determine the plasma C24hr of MK-1075 metabolite M1 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). | Day 7 at 24 hours postdose |
| BG002 | GT3 400 mg MK-1075 | Fasted GT3 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| BG003 | GT3 600 mg MK-1075 | Fasted GT3 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Fasted GT1 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days
| OG001 | GT1 MK-1075 600 mg | Fasted GT1 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| OG002 | GT3 400 mg MK-1075 | Fasted GT3 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
| OG003 | GT3 600 mg MK-1075 | Fasted GT3 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days |
|
|
| Primary | Number of Participants Who Discontinued Treatment Due to an AE | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Participants who received at least one dose of the investigational drug. | Posted | Count of Participants | Participants | Up to Day 7 |
|
|
|
| Primary | Change From Baseline in Maximum log10 HCV RNA Following Multiple Dose Oral Administration of MK-1075 | Blood was collected on Days 1, 3, 4, 5, 6, 7, 21, 28 and 42, where baseline measurement was defined as the measurement obtained pre-dose on the first day of dosing. Change from baseline in log10 HCV RNA levels, was determined, and the maximum reduction in HCV RNA was analyzed by an ANOVA model with a fixed effect for treatment. The primary hypothesis is, with a posterior probability larger than 70%, there is at least a 3 log10 reduction from baseline in HCV RNA. | Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of major protocol deviations. | Posted | Least Squares Mean | 90% Confidence Interval | log10 IU/mL | Day 1 (pre-dose, 2, 4, 8, 12, and 24 hours postdose); Days 3, 4, 5, 6 (pre-dose); Day 7 (predose, 4, 12, 24, 48, 72, 96, 120, and 192 hours postdose); Days 21, 28 and 42 |
|
|
|
| Secondary | Area Under the Plasma Concentration Time Curve From Time 0 to 24 Hrs (AUC 0-24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC 0-24hr of MK-1075 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. | AUC 0-24hr were not determined because concentrations of MK-1075 at 24 hour were not quantifiable | Posted | Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose |
|
|
| Secondary | AUC 0-24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC 0-24hr of the MK-1075 metabolite M1 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. | Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of major protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*μmol/L | Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose |
|
|
|
| Secondary | Area Under the Plasma Concentration Time Curve From Time 0 to Last (AUC 0-last) of MK-1075 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 120 hours post-dose in order to determine the plasma AUC 0-last of MK-1075 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. | Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of major protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*μmol/L | Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose |
|
|
|
| Secondary | AUC 0-last of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected from pre-dose up to 120 hours post-dose in order to determine the plasma AUC 0-last of M1 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). AUC was calculated using the linear-up/log-down trapezoidal method. | Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of major protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*μmol/L | Day 7 at the following time points: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 120 hours postdose |
|
|
|
| Secondary | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-1075 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected at 24 hours post-dose in order to determine the plasma C24hr of MK- 1075 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on MK-1075 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). | C24hr were not determined because concentrations of MK-1075 at 24 hour were not quantifiable. | Posted | Day 7 at 24 hours postdose |
|
|
| Secondary | C24hr of Metabolite M1 Following Multiple Dose Oral Administration of MK-1075 | Blood was collected at 24 hours post-dose in order to determine the plasma C24hr of MK-1075 metabolite M1 for pooled GT1 and GT3 genotypes. A non-compartmental analysis on M1 plasma concentrations was performed where actual sampling times, converted to elapsed time relative to dosing times, by using the software Phoenix WinNonlin® Professional (Version 6.3). | Participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers such considerations as exposure to treatment, availability of measurements and absence of major protocol deviations. | Posted | Geometric Mean | Geometric Coefficient of Variation | μmol/L | Day 7 at 24 hours postdose |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | GT3 Pre-treatment | GT3 participants were enrolled for 4 weeks prior to randomization and treatment. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG002 | GT1 400 mg MK-1075 | Fasted GT1 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days | 0 | 3 | 0 | 3 | 3 | 3 |
| EG003 | GT1 600 mg MK-1075 | Fasted GT1 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days | 0 | 3 | 0 | 3 | 2 | 3 |
| EG004 | GT3 MK-1075 400 mg | Fasted GT3 participants were administered 400 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG005 | GT3 600 mg MK-1075 | Fasted GT3 participants were administered 600 mg MK-1075 in tablet form, orally, once daily for 7 consecutive days. | 0 | 3 | 0 | 3 | 2 | 3 |
| EG006 | GT1 Post-study | After treatment Day 7, GT1 participants were monitored for AEs up to Day 42. | 0 | 6 | 0 | 6 | 1 | 6 |
| EG007 | GT3 Post-study | After treatment Day 7, GT3 participants were monitored for AEs up to Day 42. | 0 | 6 | 0 | 6 | 1 | 6 |
| Dizziness | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 18.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 18.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 18.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 18.1 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |