A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01938625
• Collaborator: (none)
• Enrollment: 35
• Locations: 6
• Arms: 2
• Actual Duration (Months): 19.5
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate effect of steady-state (when the amount of drug administered (in a given time period is equal to the amount of drug eliminated in that same period) of simeprevir and daclatasvir on the steady-state pharmacokinetics (what a medication does to the body) of cyclosporine (applicable to Part 1 only) and tacrolimus when administered as a combinational regimen in post-orthotopic liver transplantation (OLT) participants with recurrent hepatitis C virus (HCV) genotype 1b infection and effectiveness of a 24-week treatment regimen containing simeprevir, daclatasvir, and ribavirin (RBV) with respect to the proportion of HCV genotype 1b infected post-OLT participants achieving sustained virologic response 12 weeks after end of treatment.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Simeprevir; Drug: Daclatasvir; Drug: Ribavirin; Drug: Cyclosporine; Drug: Tacrolimus	Phase 2

Detailed Description

This is an open-label (all participants of this study know the identity of the intervention) and multicenter (study conducted at multiple sites) study. This study will be conducted in 2 parts. Both the parts of the study will consist of screening phase (4 weeks), treatment period (24 weeks), and a post-treatment follow-up (24 weeks). A total of 30 participants will be enrolled in Part 1 and Part 2 of the study. A minimum of 9 participants were planned to receive cyclosporine as stable immunosuppressant therapy and a minimum of 9 participants were planned to receive tacrolimus as stable immunosuppressant therapy during Part 1. All participants will be receiving tacrolimus as stable immunosuppressant therapy during Part 2. In Part 1 of the study, participants with Metavir score of F1-F2, will receive a combination of study drugs - simeprevir, daclatasvir, and ribavirin for 24 weeks. In Part 2 of the study, participants with Metavir score F1-F4 will receive a dosing regimen of study drugs based on the data from Part 1 of the study. Safety evaluations will include assessments of adverse events, clinical laboratory tests, urinalysis, electrocardiogram, vital signs, and physical examination. The total study duration for each participant will be approximately 52 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2, Open-Label Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Tolerability of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052) and Ribavirin (RBV) in Subjects With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation
• Actual Study Start Date: Dec 12, 2013
• Actual Primary Completion Date: Apr 27, 2015
• Actual Study Completion Date: Jul 28, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Participants with Metavir fibrosis score F1-F2 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with cyclosporine or tacrolimus as stable immunosuppressant therapy.	Drug: Simeprevir; Participants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment.; Drug: Daclatasvir; Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.; Drug: Ribavirin; Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.; Drug: Cyclosporine; Participants will receive cyclosporine as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Cyclosporine will be administered as per the manufacturer's prescribing information for 24 weeks.; Drug: Tacrolimus; Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks.
Experimental: Part 2 Participants with Metavir fibrosis score F1-F4 will receive treatment with combinational regimen of simeprevir, daclatasvir, and ribavirin along with tacrolimus as stable immunosuppressant therapy.	Drug: Simeprevir; Participants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment.; Drug: Daclatasvir; Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.; Drug: Ribavirin; Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.; Drug: Tacrolimus; Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12) [Week 36]

   Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4) [Week 28]

   Participants were considered to have achieved SVR4 if HCV RNA levels were (<) 25 IU/mL detectable or undetectable at 4 weeks after the end of treatment.

2. Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24) [Week 48]

   Participants were considered to have achieved SVR 24 if hepatitis C virus ribonucleic acid (HCV RNA) levels were (<) 25 IU/mL detectable or undetectable at 24 weeks after the end of treatment.

3. Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable [Weeks 2, 4, 12, and 24]

   Percentage of participants with detectable and undetectable HCV RNA (<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported.

4. Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4 [Week 4]

   Percentage of participants with HCV RNA (<) 100 IU/mL at week 4 were reported.

5. Number of Participants With On-Treatment Failure [Up to Week 24 after actual EOT (week 24)]

   On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been <lower limit of quantification (LLOQ) while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to adverse events (AEs), withdrawal of consent).

6. Number of Participants With Viral Breakthrough [Up to week 24]

   Viral breakthrough is defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in participants whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment.

7. Number of Participants With Viral Relapse [Up to Week 24 after actual EOT (week 24)]

   Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Liver transplant between 6 months and 10 years prior to the screening visit

• Hepatitis C virus (HCV) genotype 1 subtype b infection confirmed at screening

• Screening HCV ribonucleic acid level greater than 10,000 IU/mL

• HCV treatment-naïve participants must not have received post orthotopic liver transplant treatment with any approved or investigational drug for the treatment of HCV

• Receiving stable immunosuppressant therapy (ie, no change in dose in the last month) with cyclosporine (only allowed in Part 1) or tacrolimus for more than 3 months prior to the screening visit

Exclusion Criteria:

• Evidence of acute or chronic hepatic decompensation after the liver transplantation (including ascites, bleeding varices or hepatic encephalopathy)

• Any liver disease of non-HCV etiology, including current evidence of graft rejection except the presence of liver steatosis

• Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of ribavirin

• Coinfection with HCV of another genotype than genotype 1b, HIV type 1 or 2 (positive HIV-1 or HIV-2 antibodies test at screening), and hepatitis B virus (hepatitis B surface antigen positive)

• Multi-organ transplant that included heart, lung, pancreas, or kidney

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Essen		Germany
2		Hamburg		Germany
3		Warszawa		Poland
4		Barcelona		Spain
5		Madrid		Spain
6		Valencia		Spain

Sponsors and Collaborators

• Janssen R&D Ireland

Investigators

• Study Director: Janssen R&D Ireland Clinical Trial, Janssen R&D Ireland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen R&D Ireland
• ClinicalTrials.gov Identifier: NCT01938625
• Other Study ID Numbers: CR102639; TMC435HPC3016; 2013-002726-23
• First Posted: Sep 10, 2013
• Last Update Posted: Nov 21, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Janssen R&D Ireland: Hepatitis C, Chronic; Recurrent Chronic Hepatitis C; Pharmacokinetics; Simeprevir; Daclatasvir; Ribavirin; Orthotopic Liver Transplantation; TMC435; BMS-790052; RBV
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Cyclosporine; Ribavirin; Simeprevir; Tacrolimus; Cyclosporins

Study Results

Participant Flow

Pre-assignment Detail	The study was conducted in 2 parts (part 1 and part 2) to sequentially enroll the participants. All analyses were conducted on the overall study population (part 1 and part 2 combined).

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Period Title: Overall Study
STARTED	10	25
COMPLETED	10	23
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Cyclosporine	Tacrolimus	Total
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.	Total of all reporting groups
Overall Participants	10	25	35
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64.5	61	62
Sex: Female, Male (Count of Participants)
Female	4 40%	9 36%	13 37.1%
Male	6 60%	16 64%	22 62.9%
Region of Enrollment (Count of Participants)
Germany	1 10%	6 24%	7 20%
Spain	3 30%	9 36%	12 34.3%
Poland	0 0%	7 28%	7 20%
Italy	6 60%	3 12%	9 25.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After the End of Treatment (SVR 12)
Description	Participants were considered to have achieved SVR12 if hepatitis C virus ribonucleic acid (HCV RNA) levels were less than (<) 25 international unit per milliliter (IU/mL) detectable or undetectable at 12 weeks after the end of treatment.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Number (95% Confidence Interval) [percentage of participants]	100 1000%	88 352%

2. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 4 Weeks After the End of Treatment (SVR 4)
Description	Participants were considered to have achieved SVR4 if HCV RNA levels were (<) 25 IU/mL detectable or undetectable at 4 weeks after the end of treatment.
Time Frame	Week 28

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Number (95% Confidence Interval) [percentage of participants]	100 1000%	88 352%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 24 Weeks After the End of Treatment (SVR 24)
Description	Participants were considered to have achieved SVR 24 if hepatitis C virus ribonucleic acid (HCV RNA) levels were (<) 25 IU/mL detectable or undetectable at 24 weeks after the end of treatment.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Number (95% Confidence Interval) [percentage of participants]	100 1000%	88 352%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA (< 25 IU/mL Undetectable) and HCV RNA < 25 IU/mL Detectable
Description	Percentage of participants with detectable and undetectable HCV RNA (<) 25 IU/mL during treatment at Weeks 2,4, 12, and 24 were reported.
Time Frame	Weeks 2, 4, 12, and 24

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Week 2: <25 IU/mL detectable	30 300%	36 144%
Week 2: <25 IU/mL undetectable	10 100%	12 48%
Week 4: <25 IU/mL detectable	30 300%	24 96%
Week 4: <25 IU/mL undetectable	70 700%	68 272%
Week 12: <25 IU/mL detectable	0 0%	0 0%
Week 12: <25 IU/mL undetectable	100 1000%	96 384%
Week 24: <25 IU/mL detectable	0 0%	0 0%
Week 24: <25 IU/mL undetectable	100 1000%	100 400%

5. Secondary Outcome

Title	Percentage of Participants With HCV RNA (<) 100 IU/mL at Week 4
Description	Percentage of participants with HCV RNA (<) 100 IU/mL at week 4 were reported.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Number [percentage of participants]	100 1000%	100 400%

6. Secondary Outcome

Title	Number of Participants With On-Treatment Failure
Description	On-treatment failure is defined as participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. This was to include participants with: 1) Viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA of >100 IU/mL in participants whose HCV RNA had previously been <lower limit of quantification (LLOQ) while on treatment; 2) Other with confirmed detectable HCV RNA at the actual end of treatment (example, completed, discontinued due to adverse events (AEs), withdrawal of consent).
Time Frame	Up to Week 24 after actual EOT (week 24)

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Number [participants]	0 0%	3 12%

7. Secondary Outcome

Title	Number of Participants With Viral Breakthrough
Description	Viral breakthrough is defined as a confirmed increase of >1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of >100 IU/mL in participants whose HCV RNA levels had previously been below the limit of quantification (<25 IU/mL detectable) or undetectable (<25 IU/mL undetectable) while on study treatment.
Time Frame	Up to week 24

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Number [participants]	0 0%	3 12%

8. Secondary Outcome

Title	Number of Participants With Viral Relapse
Description	Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up.
Time Frame	Up to Week 24 after actual EOT (week 24)

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) analysis set included all enrolled participants who took at least 1 dose of investigational medication.

Arm/Group Title	Cyclosporine	Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.	Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
Measure Participants	10	25
Number [participants]	0 0%	0 0%

Adverse Events

Time Frame	Up to 52 Weeks
Arm/Group Title	Cyclosporine		Tacrolimus
Arm/Group Description	Participants received simeprevir (SMV) 150 milligram (mg) once daily (qd) or once every other day (qod) as applicable with food and daclatasvir (DCV) 60 mg qd with food and ribavirin (RBV) 1000 or 1200 milligram per day (mg/day) twice daily (bid) with food for 24 Weeks along with cyclosporine as immunosuppressant therapy for more than 3 months prior to the screening visit.		Participants received SMV 150 mg qd or qod as applicable with food and DCV 60 mg qd with food and RBV 1000 or 1200 mg/day bid with food for 24 Weeks along with tacrolimus as immunosuppressant therapy for more than 3 months prior to the screening visit.
All Cause Mortality
	Cyclosporine		Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cyclosporine		Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		4/25 (16%)
Blood and lymphatic system disorders
Anaemia	0/10 (0%)		1/25 (4%)
Gastrointestinal disorders
Abdominal Pain Upper	0/10 (0%)		1/25 (4%)
Diarrhoea	1/10 (10%)		0/25 (0%)
Vomiting	0/10 (0%)		1/25 (4%)
General disorders
Pyrexia	3/10 (30%)		0/25 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/10 (0%)		1/25 (4%)
Infections and infestations
Escherichia Urinary Tract Infection	1/10 (10%)		0/25 (0%)
Genital Herpes	1/10 (10%)		0/25 (0%)
Pneumonia	0/10 (0%)		1/25 (4%)
Urinary Tract Infection	0/10 (0%)		1/25 (4%)
Injury, poisoning and procedural complications
Facial Bones Fracture	1/10 (10%)		0/25 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma	0/10 (0%)		1/25 (4%)
Nervous system disorders
Hepatic Encephalopathy	0/10 (0%)		1/25 (4%)
Loss of Consciousness	0/10 (0%)		1/25 (4%)
Syncope	1/10 (10%)		0/25 (0%)
Renal and urinary disorders
Acute Kidney Injury	1/10 (10%)		0/25 (0%)
Micturition Disorder	0/10 (0%)		1/25 (4%)
Renal Impairment	1/10 (10%)		0/25 (0%)
Reproductive system and breast disorders
Prostatitis	1/10 (10%)		0/25 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/10 (10%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Cyclosporine		Tacrolimus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		23/25 (92%)
Blood and lymphatic system disorders
Anaemia	7/10 (70%)		11/25 (44%)
Haemolytic Anaemia	0/10 (0%)		2/25 (8%)
Leukopenia	1/10 (10%)		1/25 (4%)
Thrombocytopenia	1/10 (10%)		0/25 (0%)
Ear and labyrinth disorders
Vertigo	0/10 (0%)		3/25 (12%)
Eye disorders
Ocular Icterus	1/10 (10%)		1/25 (4%)
Visual Acuity Reduced	1/10 (10%)		0/25 (0%)
Gastrointestinal disorders
Abdominal Pain	1/10 (10%)		0/25 (0%)
Aphthous Stomatitis	1/10 (10%)		1/25 (4%)
Constipation	1/10 (10%)		1/25 (4%)
Diarrhoea	1/10 (10%)		3/25 (12%)
Lip Dry	1/10 (10%)		0/25 (0%)
Nausea	1/10 (10%)		3/25 (12%)
Tongue Dry	1/10 (10%)		0/25 (0%)
Vomiting	1/10 (10%)		2/25 (8%)
General disorders
Asthenia	5/10 (50%)		7/25 (28%)
Fatigue	2/10 (20%)		1/25 (4%)
Gait Disturbance	1/10 (10%)		0/25 (0%)
General Physical Health Deterioration	0/10 (0%)		2/25 (8%)
Mucous Membrane Disorder	1/10 (10%)		0/25 (0%)
Oedema Peripheral	1/10 (10%)		0/25 (0%)
Pyrexia	1/10 (10%)		1/25 (4%)
Hepatobiliary disorders
Cholangitis	1/10 (10%)		0/25 (0%)
Hyperbilirubinaemia	2/10 (20%)		2/25 (8%)
Infections and infestations
Oral Candidiasis	0/10 (0%)		2/25 (8%)
Oral Herpes	1/10 (10%)		1/25 (4%)
Urinary Tract Infection	1/10 (10%)		2/25 (8%)
Injury, poisoning and procedural complications
Fall	1/10 (10%)		0/25 (0%)
Investigations
Blood Bilirubin Increased	0/10 (0%)		2/25 (8%)
Metabolism and nutrition disorders
Decreased Appetite	1/10 (10%)		0/25 (0%)
Hyperuricaemia	1/10 (10%)		1/25 (4%)
Musculoskeletal and connective tissue disorders
Back Pain	0/10 (0%)		2/25 (8%)
Muscle Spasms	1/10 (10%)		0/25 (0%)
Myalgia	1/10 (10%)		2/25 (8%)
Nervous system disorders
Dysgeusia	1/10 (10%)		0/25 (0%)
Headache	1/10 (10%)		4/25 (16%)
Restless Legs Syndrome	1/10 (10%)		0/25 (0%)
Psychiatric disorders
Anger	1/10 (10%)		1/25 (4%)
Hallucination, Visual	1/10 (10%)		0/25 (0%)
Renal and urinary disorders
Renal Failure	1/10 (10%)		0/25 (0%)
Reproductive system and breast disorders
Vulvovaginal Pain	1/10 (10%)		0/25 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/10 (20%)		3/25 (12%)
Dysphonia	1/10 (10%)		0/25 (0%)
Dyspnoea	2/10 (20%)		1/25 (4%)
Productive Cough	1/10 (10%)		0/25 (0%)
Pulmonary Hypertension	1/10 (10%)		0/25 (0%)
Skin and subcutaneous tissue disorders
Dry Skin	0/10 (0%)		2/25 (8%)
Erythema	1/10 (10%)		0/25 (0%)
Photosensitivity Reaction	1/10 (10%)		3/25 (12%)
Pruritus	1/10 (10%)		5/25 (20%)
Rash	1/10 (10%)		1/25 (4%)
Vascular disorders
Hypertension	0/10 (0%)		3/25 (12%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.