An Open-label Randomized Multicenter Phase III Clinical S... | NCT02103439

NCT02103439

Status Module

Label	Type	Description	Intervention Names
Algeron	Experimental	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg)	Drug: Algeron
PegIntron	Active Comparator	PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg).	Drug: PegIntron

Name	Type	Description	Arm Group Labels	Other Names
Algeron	Drug	1.5 µg/kg of body weight subcutaneously, once a week	Algeron

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Early Virological Response	Proportion of randomized patients achieving early virologic response - negative polymerase chain reaction result for Hepatitis C Virus ribonucleic acid (< 15 IU/ml) or ≥ 2log10 decrease of viral load after 12 weeks of study treatment	12 weeks
Early Virological Response in Patients With Different Hepatitis C Virus Genotypes	Proportion of randomized patients with different Hepatitis C Virus (HCV) genotypes achieving early virologic response - negative polymerase chain reaction result for HCV ribonucleic acid (< 15 IU/ml) or ≥ 2log10 decrease of viral load after 12 weeks of study treatment	12 weeks

Secondary Outcomes

Measure	Description	Time Frame
Rapid Virological Response	Proportion of randomized patients achieving rapid virologic response - negative polymerase chain reaction result for Hepatitis C Virus ribonucleic acid (< 15 IU/ml) after 4 weeks of treatment	4 weeks
Rapid Virological Response in Patients With Different Hepatitis C Virus Genotypes

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed Informed Consent Form.
Chronic hepatitis C (genotypes 1а, 1b, 2, 3, 4) confirmed by positive result of hepatitis C virus ribonucleic acid during > 6 months before screening visit or accompanied with increase in alanine aminotransferase (ALT) level > 6 months before screening visit.
Confirmed Human Immunodeficiency Virus-1 infection based on enzyme-linked immunosorbent assay and immune blotting results.
Clinically sustained phase of Human Immunodeficiency Virus-1 infection with absence of active opportunistic Human Immunodeficiency Virus-associated diseases for at least 30 calendar days before inclusion in the study.
Level of CD4+-lymphocytes is not less than 500 cells/mm3 for patients not requiring highly active antiretroviral therapy and which will not be assigned to antiretroviral therapy during the study period.
For patients receiving sustained highly active antiretroviral therapy for not less than 12 weeks and planning to continue comply with this treatment regimen during the following 24 weeks, level of CD4+-lymphocytes ≥300 cells/mm3, Human Immunodeficiency Virus ribonucleic acid ≤50 copies/ml.
Men and women aged 18 to 70 inclusively.
Body mass index in the range of 18 - 30 kg/m2 inclusively .
Preserved protein-synthetizing liver function (International Normalized Ratio < 1.7, albumin > 35 g/l).
Absence of signs of hepatic encephalopathy and ascites according to clinical examination and ultrasound examination.
Patients with preserved child-bearing potential and their partners agree to use barrier method of contraception during the whole period of therapy and during 7 months after the treatment completion.
Documentary confirmed results of liver elastography (fibroscan) during last year before enrollment in the study or patient agreement to undergo this examination during screening.

Exclusion Criteria:

Intolerance of alfa-interferons, ribavirin or any components of tested drug product based on medical history.
Presence of hepatitis B, A, E markers.
Presence of documentary confirmed clinically significant concurrent liver diseases (alcoholic liver cirrhosis, drug-induced liver cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, non-alcoholic steatohepatitis, biliary cirrhosis etc.).
Past history of Hepatitis C Virus treatment with interferon alfa or pegylated interferon alfa.
For patients receiving sustained highly active antiretroviral therapy - presence of nevirapine, stavudine, zidovudine, didanosine in treatment regimen.
Use of injectable and non-injectable interferons alfa/ interferon inducers for any indication (except for hepatitis C), radiotherapy, cytotoxic chemotherapy for one month prior to inclusion in the study.
Cholestic hepatitis (level of direct bilirubin, alkaline phosphatase, gamma glutamyltransferase, exceeding upper normal limit in > 5 times).
Decompensated liver cirrhosis confirmed with results of laboratory analyses (Child-Pugh class B, C) or ultrasound examination.
Any documentary confirmed autoimmune diseases (such as Crohn's disease, ulcerative colitis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, scleroderma, autoimmune hemolytic anemia, severe psoriasis).
Deviations of hematologic (hemoglobin less than lower normal limit; neutrophils < 1.5 x 10^9/l; thrombocytes < 90 x 10^9/ l) and biochemical (creatinine level > 1.5 times higher upper normal limit, ALT is > 10 times higher upper normal limit) parameters.
Documentary confirmed diagnosis of hemoglobinopathy (for example, thalassemia, sickle-cell anemia).
Severe depression, schizophrenia, any other mental disorders which according to the investigator are contraindications for antiviral treatment.
Epilepsy and/or central nervous system disorder.
Disorder of thyroid function (level of thyroid stimulating hormone out of the normal range).
Documentary confirmed or suspected hepatocellular carcinoma based on the results of alfa-fetoprotein (AFP) assay ≥ upper normal limit.
Antinuclear antibodies (ANA) titer measured at screening is not less than 1:640 or documentary confirmed signs of autoimmune hepatitis based on the results of biopsy.
Documentary confirmed malignant neoplasms.
Documentary confirmed lung diseases associated with respiratory failure.
Treatment of Human Immunodeficiency Virus-1 with immunotherapeutic vaccines within 90 days prior to screening.
Necessity in assignment of antimycobacterial therapy.
Pregnancy, lactation period.
Documentary confirmed retinopathy (for example, cytomegalovirus retinitis, macular degeneration).
Severe concurrent diseases (for example, severe arterial hypertension, sever coronary heart disease, heart failure, decompensated diabetes mellitus and other) which are contraindications for antiviral therapy according to the investigator opinion.

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Gregory Moshkovich, M.D.	State Institution of Nizhny Novgorod region "Regional Center for Prevention and Control of AIDS and other infectious diseases"	Principal Investigator
Firaya Nagimova, PhD	State Public Healthcare Institution National Center for the Prevention and Control of AIDS and other infectious diseases of the Ministry of Health of the Republic of Tatarstan	Principal Investigator
Oleg Kozyrev, PhD	State Healthcare Institution "Volgograd Regional Center for the Prevention and Control of AIDS and infectious diseases"	Principal Investigator
Andrey Shuldyakov, M.D., PhD	State Budgetary Higher Vocational Education Institution V.I. Razumovsky Saratov State University of medicine	Principal Investigator
Vadim Rassokhin, PhD	State Healthcare Institution Center for the Prevention and Control of AIDS and infectious diseases of the city, St.Petersburg CityHealth Department	Principal Investigator
Lidia Sklar, M.D., PhD	State Budgetary Higher Vocational Education Institution Pacific State Medical University, Ministry of Health of the Russian Federation	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
State Public Healthcare Institution National Center for the Prevention and Control of AIDS and other infectious diseases of the Ministry of Health of the Republic of Tatarstan		Kazan'	Tatarstan Republic	420097	Russia

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Algeron	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Algeron	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
BG001	PegIntron	PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00070 BG00170 BG002140

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

Early Virological Response

Proportion of randomized patients achieving early virologic response - negative polymerase chain reaction result for Hepatitis C Virus ribonucleic acid (< 15 IU/ml) or ≥ 2log10 decrease of viral load after 12 weeks of study treatment

Posted

Number

percentage of patients

12 weeks

ID	Title	Description
OG000	Algeron	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG001	PegIntron	PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week

Units	Counts
Participants	OG00070 OG00170

Title

Denominators

Categories

Title	Measurements
	OG00090.0 OG00181.4

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		0.227						2-Sided								Non-Inferiority or Equivalence	the lower limit of the 95% confidence interval for the difference in proportions between the difference in the early virological response rate with Algeron and PegIntron should be higher than the non-inferiority margin of 0.2 (-20%)

Secondary

Rapid Virological Response

Proportion of randomized patients achieving rapid virologic response - negative polymerase chain reaction result for Hepatitis C Virus ribonucleic acid (< 15 IU/ml) after 4 weeks of treatment

Posted

Number

percentage of patients

4 weeks

ID	Title	Description
OG000	Algeron	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG001	PegIntron	PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week

Units	Counts
Participants

Secondary

Rapid Virological Response in Patients With Different Hepatitis C Virus Genotypes

Proportion of randomized patients with different Hepatitis C Virus (HCV) genotypes achieving rapid virological response - negative polymerase chain reaction result for HCV ribonucleic acid (< 15 IU/ml) after 4 weeks of treatment

Posted

Number

percentage of patients

4 weeks

ID	Title	Description
OG000	Algeron - HCV-1	Patients with HCV genotype 1, received Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG001	Algeron - HCV-2/3	Patients with HCV genotype 2 or 3, received Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG002	PegIntron - HCV-1	Patients with HCV genotype 1, received PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week

Secondary

Viral Breakthrough

Proportion of patients in each groups with level of Hepatitis C Virus ribonucleic acid > 15 IU/ml after Hepatitis C Virus ribonucleic acid was not present or Hepatitis C Virus ribonucleic acid was increased by more than 1log10 from baseline at 4 or 12 weeks of treatment

Posted

Number

percentage of patients

screening data and at 4 or 12 weeks of treatment.

ID	Title	Description
OG000	Algeron	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG001	PegIntron	PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week

Units	Counts
Participants

Primary

Early Virological Response in Patients With Different Hepatitis C Virus Genotypes

Proportion of randomized patients with different Hepatitis C Virus (HCV) genotypes achieving early virologic response - negative polymerase chain reaction result for HCV ribonucleic acid (< 15 IU/ml) or ≥ 2log10 decrease of viral load after 12 weeks of study treatment

Posted

Number

percentage of patients

12 weeks

ID	Title	Description
OG000	Algeron - HCV-1	Patients with HCV genotype 1, received Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG001	Algeron - HCV-2/3	Patients with HCV genotype 2 or 3, received Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG002	PegIntron - HCV-1	Patients with HCV genotype 1, received PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week

Secondary

Biochemical Response

Proportion of patients in each group with alanine aminotransferase level ≤ upper normal limit after 12 weeks of therapy

Posted

Number

percentage of patients

12 weeks

ID	Title	Description
OG000	Algeron	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week
OG001	PegIntron	PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Algeron	Algeron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg) Algeron: 1.5 µg/kg of body weight subcutaneously, once a week			0	70	70	70
EG001	PegIntron	PegIntron at a dose of 1.5 µg/kg of body weight subcutaneously, once a week, and Rebetol, orally, at a daily dose of 800 mg (for body weight <65 kg), 1,000 mg (for body weight 65 - 85 kg), 1,200 mg (for body weight 86 - 105 kg) or 1,400 mg (for body weight > 105 kg). PegIntron: 1.5 µg/kg of body weight subcutaneously, once a week The safety analysis included 71 patients received at least 1 dose of PegIntron (taking into account one patient withdrawn at early stages of the study due to a protocol violation [previous treatment of hepatitis C with interferon alfa], who was withdrawn from the mITT-analysis)			2	71	69	71

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Flu-like syndrome	General disorders	Systematic Assessment	EG00046 events38 affected70 at risk EG00187 events41 affected71 at risk
Asthenia (weakness, fatigue)	General disorders	Systematic Assessment	EG00025 events17 affected70 at risk EG00123 events16 affected71 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00038 events12 affected70 at risk EG00125 events13 affected71 at risk
Irritability, emotional lability	Psychiatric disorders	Systematic Assessment	EG0004 events4 affected70 at risk EG0014 events4 affected71 at risk
Sleep disorders	Nervous system disorders	Systematic Assessment	EG0006 events4 affected70 at risk EG0013 events3 affected71 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00021 events7 affected70 at risk EG0018 events2 affected71 at risk
Stomach pain	Gastrointestinal disorders	Systematic Assessment	EG0009 events7 affected70 at risk EG0015 events5 affected71 at risk
Decreased appetite	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected70 at risk EG0011 events1 affected71 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0003 events3 affected70 at risk EG0017 events4 affected71 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00011 events7 affected70 at risk EG00118 events6 affected71 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0007 events4 affected70 at risk EG00110 events6 affected71 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG00016 events4 affected70 at risk EG0016 events3 affected71 at risk
Skin itch	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0007 events4 affected70 at risk EG0012 events2 affected71 at risk
Skin redness	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0005 events5 affected70 at risk EG0011 events1 affected71 at risk
Skin dryness and exfoliation	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0004 events4 affected70 at risk EG0012 events2 affected71 at risk
Leucopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00067 events60 affected70 at risk EG00169 events59 affected71 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG00067 events53 affected70 at risk EG00166 events51 affected71 at risk
Lymphopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00052 events43 affected70 at risk EG00162 events55 affected71 at risk
Decreased level of CD4+ lymphocytes	Blood and lymphatic system disorders	Systematic Assessment	EG0008 events8 affected70 at risk EG0016 events6 affected71 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Systematic Assessment	EG00039 events39 affected70 at risk EG00137 events36 affected71 at risk
Need in filgrastim	Blood and lymphatic system disorders	Systematic Assessment	EG0008 events8 affected70 at risk EG0012 events2 affected71 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG00050 events49 affected70 at risk EG00159 events57 affected71 at risk
Need in Rebetol dose correction due to anemia	Blood and lymphatic system disorders	Systematic Assessment	EG00012 events12 affected70 at risk EG00111 events11 affected71 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	Systematic Assessment	EG00027 events22 affected70 at risk EG00128 events26 affected71 at risk
Direct bilirubin increased	Hepatobiliary disorders	Systematic Assessment	EG00033 events31 affected70 at risk EG00134 events31 affected71 at risk
Increased albumin	Hepatobiliary disorders	Systematic Assessment	EG00017 events16 affected70 at risk EG00129 events25 affected71 at risk
Increased alanine aminotranferase	Hepatobiliary disorders	Systematic Assessment	EG00026 events25 affected70 at risk EG00118 events18 affected71 at risk
Increased aspartate aminotranferase	Hepatobiliary disorders	Systematic Assessment	EG00032 events28 affected70 at risk EG00131 events29 affected71 at risk
Increased gamma glumamyltransferase	Hepatobiliary disorders	Systematic Assessment	EG00021 events21 affected70 at risk EG00136 events31 affected71 at risk
Increased alkaline phosphotase	Hepatobiliary disorders	Systematic Assessment	EG0007 events7 affected70 at risk EG0016 events6 affected71 at risk
Hyperglycemia	Endocrine disorders	Systematic Assessment	EG0006 events6 affected70 at risk EG0018 events8 affected71 at risk
Hypoglycemia	Endocrine disorders	Systematic Assessment	EG00012 events10 affected70 at risk EG00115 events14 affected71 at risk
Increased triglycerides	Metabolism and nutrition disorders	Systematic Assessment	EG00038 events34 affected70 at risk EG00142 events37 affected71 at risk
Increased cholesterol	Metabolism and nutrition disorders	Systematic Assessment	EG00012 events11 affected70 at risk EG00117 events17 affected71 at risk
Increased thyroid stimulating hormone	Endocrine disorders	Systematic Assessment	EG0004 events4 affected70 at risk EG0012 events2 affected71 at risk
Increased creatinine	Renal and urinary disorders	Systematic Assessment	EG00011 events11 affected70 at risk EG0016 events6 affected71 at risk
Hyperemia	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 events2 affected70 at risk EG0014 events4 affected71 at risk

ID	Term
D008107	Liver Diseases
D004066	Digestive System Diseases
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human
D014777	Virus Diseases
D018178	Flaviviridae Infections
D012327	RNA Virus Infections

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
CTCAE 4.03 Grade 4 anemia	Blood and lymphatic system disorders		Systematic Assessment		EG0000 events0 affected70 at risk EG0011 events1 affected71 at risk
cavitary pulmonary tuberculosis	Respiratory, thoracic and mediastinal disorders		Systematic Assessment		EG0000 events0 affected70 at risk EG0011 events1 affected71 at risk