Trial Outcomes & Findings for An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients (NCT NCT01467505)

Last Updated: 2015-06-18

Results Overview

SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (\<lower limit of quantification) at 12 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

12 weeks after last planned dose of study drug (up to Week 60)

Results posted on

2015-06-18

Participant Flow

Study included Treatment-Naïve (no prior hepatitis C virus \[HCV\] therapy); Prior Relapser (prior treatment with pegylated interferon alfa/ribavirin \[Peg-IFN/RBV\] and experienced viral relapse); Prior Null/Partial Responder (prior treatment with Peg-IFN/RBV and had null/partial response); Uncategorized (could not tolerate treatment) participants.

Efficacy analyses were reported separately as per immunosuppressant regimen (reporting arms) and also separately as per prior response (in categories) (Treatment-Naive, Prior Relapser, Prior Null Responder, Prior Partial Responder, Uncategorized as well as for Total Participants), unless otherwise specified.

Participant milestones

Participant milestones
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) Participants who were receiving tacrolimus (TAC) based immunosuppressant regimen at baseline, received telaprevir (T) 1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (\<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (\>=) 75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) Participants who were receiving cyclosporine (CsA) based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Overall Study STARTED	51	10
Overall Study COMPLETED	18	7
Overall Study NOT COMPLETED	33	3

Reasons for withdrawal

Reasons for withdrawal
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) Participants who were receiving tacrolimus (TAC) based immunosuppressant regimen at baseline, received telaprevir (T) 1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (\<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (\>=) 75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) Participants who were receiving cyclosporine (CsA) based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	4	0
Overall Study Study Terminated by Sponsor	28	3

Baseline Characteristics

An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=51 Participants Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=10 Participants Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	Total n=61 Participants Total of all reporting groups
Age, Continuous	56.8 Years STANDARD_DEVIATION 4.08 • n=5 Participants	59.5 Years STANDARD_DEVIATION 2.95 • n=7 Participants	57.3 Years STANDARD_DEVIATION 4.02 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	0 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	10 Participants n=7 Participants	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after last planned dose of study drug (up to Week 60)

Population: Safety Set included all participants who received at least 1 dose of study drug. Here, n = participants evaluable for specified category for each arm, respectively.

Outcome measures

Outcome measures
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=51 Participants Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=10 Participants Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) Naive (n= 16, 2)	75.0 percentage of participants	50.0 percentage of participants
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) Prior Relapser (n= 10, 2)	60.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) Prior Null Responder (n=16, 4)	37.5 percentage of participants	50.0 percentage of participants
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) Prior Partial Responder (n= 3, 1)	66.7 percentage of participants	100.0 percentage of participants
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) Uncategorized (n= 6, 1)	50.0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) Total (n= 51, 10)	56.9 percentage of participants	70.0 percentage of participants

SECONDARY outcome

Timeframe: 24 weeks after last planned dose of study drug (up to Week 72)

Population: Safety Set included all participants who received at least 1 dose of study drug. Here, number of participants analyzed = participants evaluable for this measure and n = participants evaluable for specified category for each arm, respectively.

SVR24 was defined as an undetectable HCV RNA Levels at 24 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL.

Outcome measures

Outcome measures
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=24 Participants Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=7 Participants Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) Naive (n= 5,1)	60.0 percentage of participants	0 percentage of participants
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) Prior Relapser (n= 4,1)	25.0 percentage of participants	0 percentage of participants
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) Prior Null Responder (n=10, 4)	20.0 percentage of participants	50.0 percentage of participants
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) Prior Partial Responder (n= 0, 1)	0 percentage of participants	100.0 percentage of participants
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) Uncategorized (n= 5, 0)	20.0 percentage of participants	0 percentage of participants
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) Total (n= 24, 7)	29.2 percentage of participants	42.9 percentage of participants

SECONDARY outcome

Timeframe: Week 4

Population: Safety Set included all participants who received at least 1 dose of study drug. Here, n = participants evaluable for specified category for each arm, respectively.

The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. RVR was defined as undetectable HCV RNA 4 weeks after the start of study treatment.

Outcome measures

Outcome measures
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=51 Participants Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=10 Participants Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Percentage of Participants With Rapid Viral Response (RVR) Naive (n= 16, 2)	68.8 percentage of participants	0 percentage of participants
Percentage of Participants With Rapid Viral Response (RVR) Prior Relapser (n= 10, 2)	50.0 percentage of participants	50.0 percentage of participants
Percentage of Participants With Rapid Viral Response (RVR) Prior Null Responder (n=16, 4)	43.8 percentage of participants	25.0 percentage of participants
Percentage of Participants With Rapid Viral Response (RVR) Prior Partial Responder (n= 3, 1)	66.7 percentage of participants	100.0 percentage of participants
Percentage of Participants With Rapid Viral Response (RVR) Uncategorized (n= 6, 1)	33.3 percentage of participants	0 percentage of participants
Percentage of Participants With Rapid Viral Response (RVR) Total (n= 51, 10)	52.9 percentage of participants	30.0 percentage of participants

SECONDARY outcome

Timeframe: Week 4 and Week 12

Population: Safety Set included all participants who received at least 1 dose of study drug. Here, n = participants evaluable for specified category for each arm, respectively.

The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. eRVR was defined as undetectable HCV RNA at both 4 weeks and 12 weeks after the start of study treatment.

Outcome measures

Outcome measures
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=51 Participants Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=10 Participants Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Percentage of Participants With Extended Rapid Viral Response (eRVR) Naive (n= 16, 2)	68.8 percentage of participants	0 percentage of participants
Percentage of Participants With Extended Rapid Viral Response (eRVR) Prior Relapser (n= 10, 2)	50.0 percentage of participants	50.0 percentage of participants
Percentage of Participants With Extended Rapid Viral Response (eRVR) Prior Null Responder (n=16, 4)	37.5 percentage of participants	25.0 percentage of participants
Percentage of Participants With Extended Rapid Viral Response (eRVR) Prior Partial Responder (n= 3, 1)	66.7 percentage of participants	100.0 percentage of participants
Percentage of Participants With Extended Rapid Viral Response (eRVR) Uncategorized (n= 6, 1)	33.3 percentage of participants	0 percentage of participants
Percentage of Participants With Extended Rapid Viral Response (eRVR) Total (n= 51, 10)	51.0 percentage of participants	30.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 48

Population: Safety Set included all participants who received at least 1 dose of study drug.

On-treatment virologic failure was defined as subjects who met futility or who completed the assigned treatment duration and had detectable HCV RNA at planned end of treatment (up to 48 weeks). Data for this outcome was not planned to be reported by prior response.

Outcome measures

Outcome measures
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=51 Participants Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=10 Participants Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Percentage of Participants With On-Treatment Virologic Failure	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Safety Set included all participants who received at least 1 dose of study drug.

Any adverse change from the participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. "Study drug" includes all investigational agents (including placebo, if applicable) administered during the course of the study.

Outcome measures

Outcome measures
Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=51 Participants Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=10 Participants Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	51 participants	10 participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	11 participants	3 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks after last planned dose of study drug (up to Week 52)

Population: Due to early study termination as part of a decision to modify the drug development plan the data for this outcome measure was not collected, as planned.

Outcome measures

Outcome data not reported

Adverse Events

T/PR + Immunosuppressant Regimen (Tacrolimus)

Serious events: 11 serious events

Other events: 51 other events

Deaths: 0 deaths

T/PR + Immunosuppressant Regimen (Cyclosporine)

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
Publication restrictions are in place

Restriction type: OTHER

Measure	T/PR + Immunosuppressant Regimen (Tacrolimus) n=51 participants at risk Participants who were receiving TAC based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.	T/PR + Immunosuppressant Regimen (Cyclosporine) n=10 participants at risk Participants who were receiving CsA based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing \<75 kg and 1200 mg/day for subjects weighing \>=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
Gastrointestinal disorders Nausea	7.8% 4/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Gastrointestinal disorders Vomiting	7.8% 4/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Gastrointestinal disorders Impaired gastric emptying	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Gastrointestinal disorders Proctalgia	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Blood and lymphatic system disorders Anaemia	3.9% 2/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Infections and infestations Herpes zoster	0.00% 0/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	10.0% 1/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Infections and infestations Pneumonia	0.00% 0/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	10.0% 1/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Cardiac disorders Coronary artery disease	0.00% 0/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	10.0% 1/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
General disorders Pain	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Hepatobiliary disorders Portal vein thrombosis	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Musculoskeletal and connective tissue disorders Muscular weakness	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Nervous system disorders Cerebral infarction	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Nervous system disorders Syncope	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Nervous system disorders Transient ischaemic attack	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Psychiatric disorders Depression	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Psychiatric disorders Irritability	2.0% 1/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	0.00% 0/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/51 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.	10.0% 1/10 • Baseline up to Week 52 Other Adverse Events section includes both Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs) as Non-SAEs were not planned to be summarized separately for this study.