Pegylated Interferon Alfa-2a Maintenance Therapy and Live... | NCT00078403

ID	Type	Description	Link
10008	Registry Identifier	DAIDS ES Registry Number

Status Module

Description Module

Detailed Description

Rapid progression of liver disease to liver failure has been observed in people coinfected with HIV and HCV. This observation appears to be directly related to an increase in the rate of fibrotic progression in the liver compared to people infected with HCV alone. PEG-IFN and ribavirin are used in standard treatment of HCV. This study tested the effectiveness of using PEG-IFN in reducing the rate of liver fibrosis progression in participants coinfected with HIV and HCV who could not lower their HCV viral load to undetectable or who could not maintain their HCV viral load at undetectable on PEG-IFN and ribavirin treatment.

Participants entered Step 1 (initial run-in period) to receive 12 weeks of 180 mcg PEG-IFN subcutaneously once weekly plus 1 to 1.2 g/day ribavirin based on body weight. At week 12, HCV RNA testing was performed.

Participants with early virologic response (EVR), defined as >=2 log10 drop in HCV RNA from baseline or undetectable HCV RNA (<600 IU/ml with quantitative assay used in Step 1) at Week 12, who had tolerated Step 1 treatment, entered into Step 3 to continue receiving the Step 1 treatment for a total of 72 weeks (Arm C). Participants who did not meet the criteria for entry into Step 3 were discontinued from the study. In Step 3, participants were followed for an additional 24 weeks after treatment discontinuation to determine sustained virologic response (SVR). Initially, Step 3 participants who had a detectable HCV viral load (>=60 IU/ml with the qualitative assay used in Step 3) at Week 36 were eligible to enroll in Step 2. After early closure of Step 2, such participants remained in Step 3 until study completion.

Participants with <2 log10 drop in HCV RNA from baseline and detectable HCV RNA at Week 12 (non-EVR) discontinued Step 1 treatment. Non-EVRs who met the Step 2 eligibility criteria, were enrolled in Step 2 and randomized to receive 180 mcg PEG-IFN subcutaneously weekly for 72 weeks (Arm A) or observation for 72 weeks (Arm B). Participants who did not meet the criteria for entry into Step 2 were discontinued from the study. Step 2 of the study was closed prematurely in May 2007 due to lower than expected progression rates among the participants in the observation arm such that the primary objective could not be reached. There were no safety concerns.

Liver biopsies were conducted at study screening, and at Step 2 entry and exit until the early closure of Step 2. Medical history assessment, physical exams, and blood collection were conducted every 4-12 weeks for participants in Steps 1, 2, and 3. Participants were followed for up to 18 weeks in Step 1, followed by a total of 72 in Step 2 or by up to a total of 84 weeks in Step 3.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	Experimental	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.	Drug: Peginterferon alfa-2a Drug: Ribavirin
Arm B: OL (PEG-IFN, RBV) then OL Randomized (Observation)	Experimental	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).	Drug: Peginterferon alfa-2a Drug: Ribavirin
Arm C: OL (PEG-IFN, RBV) then OL (PEG-IFN, RBV)	Experimental	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.	Drug: Peginterferon alfa-2a Drug: Ribavirin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Peginterferon alfa-2a	Drug	180 mcg PEG-IFN subcutaneously	Arm A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) Arm B: OL (PEG-IFN, RBV) then OL Randomized (Observation)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS)	SCMFS is the difference between the Metavir fibrosis scores of the study exit and study entry liver biopsies where the difference is scaled to one year. The SCMFS assesses the annualized change in the severity of liver fibrosis on a continuous scale from -4.0 Metavir units per year (reduced fibrosis over time, a positive study outcome) to +4.0 Metavir units per year (increased fibrosis over time).	Baseline and at week 72 or premature discontinuation

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)	Qualitative plasma HCV viral load was categorized as less than 60 IU/mL vs greater than or equal to 60 IU/mL where 60 IU/mL is the lower limit of qualitative assay used in Steps 2 and 3.	Arms A and B: Weeks 0, 12, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 60, 72, 84

Eligibility Module

Eligibility Criteria

Inclusion Criteria for Step 1:

HIV infected
Stable antiretroviral therapy for at least 8 weeks prior to study entry OR have not received any antiretroviral therapy for at least 4 weeks prior to entry
HIV viral load less than 50,000 copies/ml within 6 weeks prior to study entry
CD4 count greater than 200 cells/mm^3 within 6 weeks prior to study entry
Hepatitis C virus (HCV) infected
Either HCV treatment naive OR previously treated with interferon (IFN), PEG-IFN, IFN and ribavirin, or PEG-IFN and ribavirin for at least 12 weeks and HCV RNA positive following their last course of HCV treatment
Chronic liver disease consistent with chronic viral hepatitis
At least stage I fibrosis on a liver biopsy obtained within 104 weeks of study entry
If at stage VI fibrosis, Child-Pugh-Turcotte (CPT) score of 5 or less and no more than Child-Pugh Class A
Liver enzyme (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase) levels 10 times or less than upper limit of normal
Agree to use acceptable methods of contraception

Inclusion Criteria for Step 2:

Currently enrolled in Step 1 or received 12 weeks of PEG-IFN plus ribavirin outside this study
Detectable HCV viral load and <2 log10 decrease from baseline in plasma/serum HCV viral load at Week 12.
On Step 1 study treatment for no longer than 18 weeks

Inclusion Criteria for Step 3:

Currently enrolled in Step 1
Undetectable HCV RNA or a 2-log or greater decrease in plasma/serum HCV viral load.
On Step 1 study treatment for no longer than 18 weeks

Exclusion Criteria for Steps 1 and 3:

Have received HCV treatment within 4 weeks of study entry. Participants currently receiving treatment for HCV, if non-EVRs, were considered for direct entry into Step 2, without the run-in period in Step 1.
Could not tolerate treatment with PEG-IFN, defined as missing 3 or more consecutive PEG-IFN doses during the first 12 weeks or a total of 5 doses prior to Step 3 entry. Participants who have missed doses of ribavirin will not be excluded from Step 3 entry.
Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days prior to study entry
Alpha feto protein level 400 ng/ml or greater within 24 weeks prior to study entry, or alpha feto protein level greater than 50 ng/ml and less than 400 ng/ml (unless computed tomography [CT] scan or magnetic resonance imaging [MRI] shows no evidence of hepatic tumor) within 24 weeks prior to study entry
Decompensated liver disease, including presence or history of ascites, variceal bleeding, and brain or nervous system damage as a result of liver damage
Other causes of significant liver disease, including hepatitis A or B, excess iron deposits in the liver (hemochromatosis), or homozygote alpha-1 antitrypsin deficiency
Use of systemic corticosteroids, interferon gamma, TNF-alpha inhibitors, rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir, or hydroxyurea within 2 weeks prior to study entry
Known allergy/sensitivity to PEG-IFN alfa-2a or ribavirin or their formulations
History of uncontrolled seizure disorders
Clinically active thyroid disease. Thyroid hormone replacement therapy is permitted, but thyroid-stimulating hormone (TSH) and free thyroxine index (FTI) must be in normal range.
History of autoimmune processes, including Crohn's disease, ulcerative colitis, severe psoriasis, and rheumatoid arthritis, that may be made worse by interferon use
Any systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry
Malignancy
Active coronary artery disease within 24 weeks prior to study entry
Acute or active AIDS-defining opportunistic infections within 12 weeks of study entry
Hemoglobin abnormalities (e.g., thalassemia) or any other cause of or tendency to break down red blood cells (hemolysis)
History of major organ transplantation with an existing functional graft
Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with study adherence
Uncontrolled or active depression or other psychiatric disorder, such as untreated Grade 3 psychiatric disorder, medically untreatable Grade 3 disorder, or any hospitalization within 52 weeks of study entry that, in the opinion of the investigator, may interfere with study requirements
Other serious illness or chronic medical condition that, in the opinion of the investigator, may have prevented participant's completion of the study
Pregnant or breastfeeding

Name	Affiliation	Role
Kenneth E. Sherman, MD, PhD	University of Cincinnati	Study Chair
Raymond Chung, MD	Harvard/Massachusetts General Hospital	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Therapeutics CRS		Birmingham	Alabama	35924-2050	United States
University of Southern California CRS

PubMed Identifier	Type	Citation	Retractions
15731996	Background	Brau N. Treatment of chronic hepatitis C in human immunodeficiency virus/hepatitis C virus-coinfected patients in the era of pegylated interferon and ribavirin. Semin Liver Dis. 2005 Feb;25(1):33-51. doi: 10.1055/s-2005-864780.
14562947	Background	Borgia G, Reynaud L, Gentile I, Piazza M. HIV and hepatitis C virus: facts and controversies. Infection. 2003 Aug;31(4):232-40. doi: 10.1007/s15010-003-3131-4.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
BG001	OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
BG002	OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
BG003	Total	Total of all reporting groups

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-scaled Change in Metavir Liver Fibrosis Score (SCMFS)

SCMFS is the difference between the Metavir fibrosis scores of the study exit and study entry liver biopsies where the difference is scaled to one year. The SCMFS assesses the annualized change in the severity of liver fibrosis on a continuous scale from -4.0 Metavir units per year (reduced fibrosis over time, a positive study outcome) to +4.0 Metavir units per year (increased fibrosis over time).

62 Arm A and B participants who had follow-up liver biopsy performed or those who had Week 72 potential as of May 2, 2007 but no follow-up liver biopsy. In the unadjusted ITT analysis, the participants without SCMFS available were assigned the highest SCMFS (+2).

Posted

Median

Inter-Quartile Range

Metavir units per one year (52 weeks)

Baseline and at week 72 or premature discontinuation

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Units	Counts
Participants	OG00033 OG00129 OG0020

Title

Denominators

Categories

Title	Measurements
	OG0000(0 to 1.37) OG0010(0 to 2)

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	Accrual and follow-up on Arms A and B were halted for futility at the first independent interim review of the primary endpoint conducted on May 2, 2007.	Exact Wilcoxon rank sum test		0.58	P-value is pre-specified 1-sided test that PEG slows liver fibrosis progression. Accrual and follow-up on Arms A and B were halted at interim review for lack of fibrosis progression in Arm B (control arm). P-value is unadjusted for interim analysis.													Superiority or Other (legacy)

Secondary

Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)

Qualitative plasma HCV viral load was categorized as less than 60 IU/mL vs greater than or equal to 60 IU/mL where 60 IU/mL is the lower limit of qualitative assay used in Steps 2 and 3.

All Arm A, B and C participants

Posted

Number

Participant

Arms A and B: Weeks 0, 12, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 60, 72, 84

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Secondary

Time-scaled Change in Ishak Liver Inflammation Score (SCIIS)

Liver biopsies were performed within 42 days prior to randomization between Arms A and B while the participant remained on PEG-IFN plus RBV (=entry biopsy) and again at week 72 or premature study discontinuation (=exit biopsy). SCIIS was defined as the difference between the Ishak inflammation score of the exit biopsy and the Ishak inflammation score of the entry biopsy, where the difference is scaled to one year.

All participants with SCIIS available (Complete Cases)

Posted

Median

Inter-Quartile Range

Ishak units per one year (52 weeks)

Baseline and at week 72 or premature discontinuation

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).

Secondary

Number of Participants With Anemia

Number of participants with anemia by grade (defined by hemoglobin level in grams per deciliter; g/dL). DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = hemoglobin of 8 to 9.4 g/dl; Grade 2 = 7 to 7.9 g/dl; Grade 3 = 6.5 to 6.9 g/dl; Grade 4 = below 6.5 g/dl.

All Arm A, B and C participants

Posted

Number

Participant

Up to 96 weeks

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Secondary

Number of Participants With Neutropenia

Number of participants with neutropenia by grade (defined by absolute neutrophil count [ANC] per cubic millimeter; mm^3). DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = ANC of 1000 to 1500 /mm^3; Grade 2 = 750 to 999 /mm^3; Grade 3 = 500 to 749 /mm^3; Grade 4 = below 500 /mm^3.

All Arm A, B and C participants

Posted

Number

Participant

Up to 96 weeks

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Secondary

Number of Participants With Thrombocytopenia

Number of participants with thrombocytopenia by grade (defined by platelet count per cubic millimeter; mm^3). DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = platelets of 75,000 to 99,000 /mm^3; Grade 2 = 50,000 to 74,999 /mm^3; Grade 3 = 20,000 to 49,999 /mm^3; Grade 4 = below 20,000 /mm^3.

All Arm A, B and C participants

Posted

Number

Participant

Up to 96 weeks

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Secondary

Number of Participants With Depression and/or Other Psychological Events

Depression and other psychological events. DAIDS Toxicity Grading Table (1992) was used for grading. The protocol required reporting of depression and other psychological events of Grade 3 or higher or if led to a change in treatment, regardless of grade.

All Arm A, B and C participants

Posted

Number

Participant

Up to 96 weeks

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Secondary

Number of Participants With High-grade Signs and Symptoms or Laboratory Values

Number of participants with high-grade (Grade 3 or higher) signs and symptoms or laboratory values. DAIDS Toxicity Grading Table (1992) was used for grading where Grade 1 = transient/mild discomfort, no limitation in activity, no medical intervention; Grade 2 = mild/moderate limitation in activity, some assistance, no/minimal medical intervention; Grade 3 = marked limitation in activity, some assistance, medical intervention required); Grade 4 = extreme limitation in activity, significant medical intervention, assistance, hospitalization.

All Arm A, B and C participants

Posted

Number

Participant

Up to 96 Weeks

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).

Secondary

Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations

3-level categorical of the worst of 1) premature treatment discontinuation, 2) temporary stop or 3) dose reduction. For Arm C, the worst for either PEG-IFN or RBV is summarized.

All Arm A and C participants. Arm B participants did not receive treatment.

Posted

Number

Participant

Up to 96 Weeks

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Secondary

Number of Participants Adherent to Study Medications

A categorical variable with levels adherent and non-adherent based on participants' self report. For Arm A, adherence was defined as not missing PEG within 2 weeks of visit. For Arm C, adherence was defined as not missing any PEG within 2 weeks of visit and not missing RBV within 4 days of visit.

All Arm A and Arm C participants. Arm B participants did not receive treatment.

Posted

Number

Participant

Arm A: at weeks 12, 24, 48 and 72. Arm C: at entry and weeks 12, 24, 48, 60.

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Secondary

HCV Polymorphisms

Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued.

Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued. No participants were analyzed.

Posted

Entry and week 72 (Arms A and B only).

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).

Units	Counts
Participants

Secondary

HCV-specific Immune Response in Intrahepatic Lymphocytes

Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued.

Due to premature closure of Arms A and B with insufficient number of participants for analysis, this outcome measure was not pursued. No participants were analyzed.

Posted

Entry and week 72 (Arms A and B only).

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).

Units	Counts

Secondary

Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL)

A blood sample was drawn to determine the HIV-1 viral load. HIV-1 viral load was categorized as <50 copies/mL (undetectable) or >=50 copies/mL (detectable). 50 is the lower limit of detection of the assay.

All Arm A, B, and C participants

Posted

Number

Participant

Arms A and B: Weeks 0, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 48, 60, 72, 84

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Secondary

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

Insulin resistance was evaluated by HOMA-IR, calculated as [fasting glucose (mg/dL) x fasting insulin (uIU/mL)]/405. Study protocol required fasting for at least 8 hours (nothing by mouth except medications and water) prior to specimen collection for fasting insulin and fasting glucose testing.

All Arm A, B and C participants who had HOMA-IR result available. In Arm C, metabolic testing was only performed on participants who enrolled under protocol version 1.0. The number of participants with results available at time points listed in the Time Frame are shown in the Data Table Row Titles below.

Posted

Median

Inter-Quartile Range

mg/dL x uIU/mL

Arms A and B: at entry and weeks 24, 48 and 72; Arm C: at entry and at weeks 12, 24, 36, 48, 72, 84 and 96.

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).

Secondary

Sustained Virologic Response

Sustained Virologic Response (SVR) was defined as undetectable HCV viral load (<60 IU/ml) 24 weeks after treatment discontinuation.

All Arm A, B and C participants

Posted

Number

Participant

24 weeks after end of treatment

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Secondary

Number of Participants Who Used Antianorexia Agents, Such as Megestrol and Dronabinol

Use of antianorexia agents, such as megestrol and dronabinol at any time after pre-assignment.

All Arm A, B and C participants

Posted

Number

Participant

Up to 96 weeks

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation..

Secondary

Number of Participants With Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF)

Prescription as needed of hematologic adjuvant therapies: erythropoietin (EPO), granulocyte colony-stimulating factor (GCSF), and granulocyte-monocyte colony-stimulating factor (GM-CSF) any time after pre-assignment

All Arm A, B and C participants

Posted

Number

Participant

At any time after pre-assignment

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Secondary

Weight

Participant weight in kilograms.

All Arm A, B and C participants who had weight available. The number of participants with results available at time points listed in the Time Frame are shown in the Data Table Row Titles below.

Posted

Median

Inter-Quartile Range

kilograms

Arms A and B: at entry and weeks 4, 8, 12, 16, 24, 32, 40, 48, 56, 64 and 72; Arm C: at entry and weeks 4, 8, 12, 16, 24, 36, 48, 72, 84 and 96.

ID	Title	Description
OG000	A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OG001	B: OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OG002	C: OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)	At week 12 (end of the initial run-in period - Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.	6	44	43	44
EG001	OL (PEG-IFN, RBV) Then OL Randomized (Observation)	At week 12 (end of the initial run-in period - Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.	2	42	41	42
EG002	OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)	At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & ribavirin [RBV] 1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.	37	169	166	169

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected44 at risk EG0010 affected42 at risk EG0022 affected169 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected44 at risk EG0010 affected42 at risk EG00213 affected169 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Cardiac arrest	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Coronary artery disease	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Myocardial infarction	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Basedow's disease	Endocrine disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0011 affected42 at risk EG0020 affected169 at risk
Hypothyroidism	Endocrine disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0022 affected169 at risk
Death	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Pyrexia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Pneumonia	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Blood triglycerides increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Haemoglobin decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Neutrophil count	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected44 at risk EG0011 affected42 at risk EG0020 affected169 at risk
Neutrophil count decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected44 at risk EG0011 affected42 at risk EG0023 affected169 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Cerebellar tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 affected44 at risk EG0010 affected42 at risk EG0020 affected169 at risk
Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Abnormal dreams	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected44 at risk EG0010 affected42 at risk EG0020 affected169 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected44 at risk EG0010 affected42 at risk EG0021 affected169 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected44 at risk EG0010 affected42 at risk EG0028 affected169 at risk
Fatigue	General disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected44 at risk EG0010 affected42 at risk EG00214 affected169 at risk
Pyrexia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected44 at risk EG0011 affected42 at risk EG00211 affected169 at risk
Bronchitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0002 affected44 at risk EG0010 affected42 at risk EG0029 affected169 at risk
Activated partial thromboplastin time prolonged	Investigations	MedDRA (13.0)	Systematic Assessment	EG0008 affected44 at risk EG0018 affected42 at risk EG0021 affected169 at risk
Alanine aminotransferase increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG00030 affected44 at risk EG00132 affected42 at risk EG00264 affected169 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0007 affected44 at risk EG0016 affected42 at risk EG00212 affected169 at risk
Blood bilirubin increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0002 affected44 at risk EG0010 affected42 at risk EG00219 affected169 at risk
Blood glucose abnormal	Investigations	MedDRA (13.0)	Systematic Assessment	EG00014 affected44 at risk EG0018 affected42 at risk EG00255 affected169 at risk
Blood glucose decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0003 affected44 at risk EG0012 affected42 at risk EG00214 affected169 at risk
Blood glucose increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG00011 affected44 at risk EG0017 affected42 at risk EG00216 affected169 at risk
Blood triglycerides abnormal	Investigations	MedDRA (13.0)	Systematic Assessment	EG0006 affected44 at risk EG0010 affected42 at risk EG00222 affected169 at risk
Blood uric acid increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected44 at risk EG0011 affected42 at risk EG00211 affected169 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0008 affected44 at risk EG0012 affected42 at risk EG0026 affected169 at risk
Haemoglobin decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0005 affected44 at risk EG0011 affected42 at risk EG00222 affected169 at risk
Lipase increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0005 affected44 at risk EG0016 affected42 at risk EG00213 affected169 at risk
Neutrophil count decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG00037 affected44 at risk EG00125 affected42 at risk EG002144 affected169 at risk
Platelet count decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG00021 affected44 at risk EG0019 affected42 at risk EG00258 affected169 at risk
Prothrombin time prolonged	Investigations	MedDRA (13.0)	Systematic Assessment	EG0005 affected44 at risk EG0014 affected42 at risk EG0020 affected169 at risk
Weight decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0002 affected44 at risk EG0012 affected42 at risk EG00210 affected169 at risk
Depression	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0003 affected44 at risk EG0012 affected42 at risk EG00213 affected169 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected44 at risk EG0011 affected42 at risk EG00213 affected169 at risk
Hypertension	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected44 at risk EG0011 affected42 at risk EG0024 affected169 at risk

ID	Term
D015658	HIV Infections
D006526	Hepatitis C
D008107	Liver Diseases

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases
D006525	Hepatitis, Viral, Human
D018178	Flaviviridae Infections
D006505	Hepatitis
D004066	Digestive System Diseases

ID	Term
D012263	Ribonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides