Trial Outcomes & Findings for Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus (NCT NCT01471574)

Last Updated: 2016-01-29

Results Overview

SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy. SVR12 was defined as hepatitis C virus (HCV) values lower than the lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

549 participants

Primary outcome timeframe

Follow-up Week 12

Results posted on

2016-01-29

Participant Flow

The study was conducted at 84 sites in 13 countries.

Of 549 participants enrolled, 301 were randomized to receive treatment. Of the 248 participants who were not randomized, 204 no longer met study criteria, and 44 discontinued due to other reasons.

Participant milestones

Participant milestones
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 60 mg Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received 2 daclatasvir tablets (1x30 mg and 1x60 mg), orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non--HAART Therapy Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Treatment Period STARTED	132	39	106	24
Treatment Period COMPLETED	101	29	82	21
Treatment Period NOT COMPLETED	31	10	24	3
Follow-up Period STARTED	121	34	102	24
Follow-up Period COMPLETED	114	32	95	21
Follow-up Period NOT COMPLETED	7	2	7	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 60 mg Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received 2 daclatasvir tablets (1x30 mg and 1x60 mg), orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non--HAART Therapy Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Treatment Period Lack of Efficacy	12	4	14	1
Treatment Period Adverse Event	7	3	6	1
Treatment Period Withdrawal by Subject	5	1	1	0
Treatment Period Patient Requested Discontinue Study drug	4	0	1	1
Treatment Period Lost to Follow-up	1	2	2	0
Treatment Period Patient no Longer Meets Study Criteria	1	0	0	0
Treatment Period Other	1	0	0	0
Follow-up Period Withdrawal by Subject	3	0	3	1
Follow-up Period Lost to Follow-up	4	1	3	2
Follow-up Period Death	0	0	1	0
Follow-up Period Follow-up no longer required	0	1	0	0

Baseline Characteristics

Safety and Efficacy Study of Daclatasvir (BMS-790052) Plus Pegylated Interferon-Alfa 2a and Ribavirin in Patients Coinfected With Untreated Hepatitis C Virus and HIV Virus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=132 Participants Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=39 Participants Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg n=106 Participants Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received 2 daclatasvir tablets (1x30 mg and 1x60 mg), orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg n=24 Participants Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Total n=301 Participants Total of all reporting groups
Age, Continuous	47 years STANDARD_DEVIATION 9.72 • n=5 Participants	47.9 years STANDARD_DEVIATION 9.03 • n=7 Participants	46.5 years STANDARD_DEVIATION 9.42 • n=5 Participants	36 years STANDARD_DEVIATION 9.02 • n=4 Participants	46.1 years STANDARD_DEVIATION 9.90 • n=21 Participants
Age, Customized Younger than 65 years	125 participants n=5 Participants	39 participants n=7 Participants	104 participants n=5 Participants	24 participants n=4 Participants	292 participants n=21 Participants
Age, Customized 65 years and older	7 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	0 participants n=4 Participants	9 participants n=21 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	7 Participants n=7 Participants	27 Participants n=5 Participants	11 Participants n=4 Participants	72 Participants n=21 Participants
Sex: Female, Male Male	105 Participants n=5 Participants	32 Participants n=7 Participants	79 Participants n=5 Participants	13 Participants n=4 Participants	229 Participants n=21 Participants

PRIMARY outcome

Timeframe: Follow-up Week 12

Population: The analysis was performed in all participants who received at least 1 dose of study therapy.

Outcome measures

Outcome measures
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=132 Participants Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=39 Participants Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg n=106 Participants Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received daclatasvir tablets, 90 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir 30 or 60 or 90 mg n=277 Participants Participants with prior exposure to HAART therapy, received daclatasvir tablets , either 30, 60 or 90 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for Participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg n=24 Participants Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Percentage of Participants With Sustained Virologic Response at Follow-up Week 12 (SVR12)	75 Percentage of participants Interval 67.6 to 82.4	71.8 Percentage of participants Interval 57.7 to 85.9	71.7 Percentage of participants Interval 63.1 to 80.3	73.3 Percentage of participants Interval 68.1 to 78.5	87.5 Percentage of participants Interval 74.3 to 100.0

SECONDARY outcome

Timeframe: Week 1, 2, 4, 6, 8, 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24

Population: The analysis was performed in all participants who received at least 1 dose of study therapy. On-treatment virologic response rates were not significantly different from one another among 30 mg, 60 mg, and 90 mg groups in the HAART cohort, thus these groups were combined as per pre-specified analysis plan.

Participants who achieved HCV RNA levels lower than the LLOQ i.e., 25 IU/ml, TD or TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.

Outcome measures

Outcome measures
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=277 Participants Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=24 Participants Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received daclatasvir tablets, 90 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir 30 or 60 or 90 mg Participants with prior exposure to HAART therapy, received daclatasvir tablets , either 30, 60 or 90 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for Participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Week 1	39.7 Percentage of participants	41.7 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Week 2	71.5 Percentage of participants	91.7 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Week 4	82.7 Percentage of participants	95.8 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Week 6	84.1 Percentage of participants	87.5 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Week 8	84.1 Percentage of participants	95.8 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Week 12	85.2 Percentage of participants	91.7 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Weeks 4 and 12	78.7 Percentage of participants	91.7 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) End of treatment	84.8 Percentage of participants	95.8 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Follow-up Week 12	73.3 Percentage of participants	87.5 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than The Lower Limit of Quantitation (LLOQ), Target Detected (TD) or Target Not Detected (TND) Follow-up Week 24	70.4 Percentage of participants	83.3 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Week 1, 2, 4, 6, 8, and 12 and at both Weeks 4 and 12; end of treatment; and follow-up Weeks 12 and 24

Participants who achieved HCV RNA levels lower than the LLOQ, TND. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory. HAART=highly active antiretroviral therapy.

Outcome measures

Outcome measures
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=277 Participants Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=24 Participants Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received daclatasvir tablets, 90 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir 30 or 60 or 90 mg Participants with prior exposure to HAART therapy, received daclatasvir tablets , either 30, 60 or 90 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for Participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Week 1	9 Percentage of participants	16.7 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Week 2	33.9 Percentage of participants	50 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Week 4	64.3 Percentage of participants	91.7 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Week 6	74.4 Percentage of participants	87.5 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Week 8	78 Percentage of participants	95.8 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Week 12	81.2 Percentage of participants	91.7 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Weeks 4 and 12	61.4 Percentage of participants	87.5 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) End of treatment	84.8 Percentage of participants	95.8 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Follow-up Week 12	73.3 Percentage of participants	87.5 Percentage of participants	—	—	—
Percentage of Participants Who Achieved Hepatitis C Virus (HCV) RNA Levels Lower Than the Lower Limit of Quantitation (LLOQ), Target Not Detected (TND) Follow-up Week 24	70.4 Percentage of participants	83.3 Percentage of participants	—	—	—

SECONDARY outcome

Timeframe: End of treatment (up to Week 48)

Population: The analysis was performed in all participants who received at least 1 dose of study therapy

Participants who received HAART, maintained HIV RNA \<40 copies/mL, and experienced confirmed HIV RNA ≥ 400 copies/mL were determined.

Outcome measures

Outcome measures
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=132 Participants Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=39 Participants Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg n=106 Participants Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received daclatasvir tablets, 90 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir 30 or 60 or 90 mg n=277 Participants Participants with prior exposure to HAART therapy, received daclatasvir tablets , either 30, 60 or 90 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for Participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL HIV RNA <40 copies/mL	88.6 Percentage of participants Interval 83.2 to 94.1	89.7 Percentage of participants Interval 80.2 to 99.3	93.4 Percentage of participants Interval 88.7 to 98.1	90.6 Percentage of participants Interval 87.2 to 94.1	—
Percentage of Participants Who Received Highly Active Antiretroviral Therapy (HAART), Maintained HIV RNA <40 Copies/mL, and Experienced Confirmed HIV RNA ≥400 Copies/mL HIV RNA ≥400 copies/mL	0.0 Percentage of participants Interval 0.0 to 0.0	2.6 Percentage of participants Interval 0.0 to 7.5	0.0 Percentage of participants Interval 0.0 to 0.0	0.4 Percentage of participants Interval 0.0 to 1.1	—

SECONDARY outcome

Timeframe: Follow-up Week 12

Population: The analysis was performed in all participants who received at least 1 dose of study therapy. Here 'n' signifies number of participants evaluable at the specified time-point.

Percentages calculated as number of responders/number who received treatment.

Outcome measures

Outcome measures
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=132 Participants Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=39 Participants Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg n=106 Participants Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received daclatasvir tablets, 90 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir 30 or 60 or 90 mg n=277 Participants Participants with prior exposure to HAART therapy, received daclatasvir tablets , either 30, 60 or 90 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for Participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg n=24 Participants Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene CC Genotype (n=36, 14, 39, 89, 6)	94.4 Percentage of participants Interval 87.0 to 100.0	92.9 Percentage of participants Interval 79.4 to 100.0	79.5 Percentage of participants Interval 66.8 to 92.2	87.6 Percentage of participants Interval 80.8 to 94.5	100.0 Percentage of participants Interval 100.0 to 100.0
Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene CT Genotype (n=72, 22, 50,144, 15)	66.7 Percentage of participants Interval 55.8 to 77.6	63.6 Percentage of participants Interval 43.5 to 83.7	70.0 Percentage of participants Interval 57.3 to 82.7	67.4 Percentage of participants Interval 59.7 to 75.0	93.3 Percentage of participants Interval 80.7 to 100.0
Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene TT Genotype (n=22, 3, 12, 37, 2)	68.2 Percentage of participants Interval 48.7 to 87.6	33.3 Percentage of participants Interval 0.0 to 86.7	58.3 Percentage of participants Interval 30.4 to 86.2	62.2 Percentage of participants Interval 46.5 to 77.8	50.0 Percentage of participants Interval 0.0 to 100.0
Percentage of Participants With Sustained Virologic Response (SVR12) by rs12979860 Single Nucleotide Polymorphism (SNP) in the IL28B Gene Not reported (n=2, 0, 5, 7, 1)	100.0 Percentage of participants Interval 100.0 to 100.0	0.0 Percentage of participants Interval 0.0 to 0.0	60.0 Percentage of participants Interval 17.1 to 100.0	71.4 Percentage of participants Interval 38.0 to 100.0	0.0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: From Day 1 to 7 days post last dose of study treatment (up to Week 48)

Population: The analysis was performed in all participants who received at least 1 dose of study drug.

Adverse event was defined as any new unfavorable symptom, sign, or disease or worsening of a pre-existing condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threating, an important medical event, or a congenital anomaly/birth defect; or required prolonged hospitalization. HAART=highly active antiretroviral therapy.

Outcome measures

Outcome measures
Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=132 Participants Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=39 Participants Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg n=106 Participants Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received daclatasvir tablets, 90 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir 30 or 60 or 90 mg n=277 Participants Participants with prior exposure to HAART therapy, received daclatasvir tablets , either 30, 60 or 90 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for Participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg n=24 Participants Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation Deaths	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants
Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation SAEs	12 Participants	6 Participants	6 Participants	24 Participants	0 Participants
Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation Grade 3 to 4 AEs	46 Participants	12 Participants	35 Participants	93 Participants	4 Participants
Number of Participants Who Died and With Serious Adverse Event (SAEs), Grade 3 to 4 Adverse Events (AEs), and AEs Leading to Discontinuation AEs leading to discontinuation	7 Participants	4 Participants	6 Participants	17 Participants	1 Participants

Adverse Events

Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg

Serious events: 12 serious events

Other events: 122 other events

Deaths: 0 deaths

HAART Therapy: Daclatasvir, 60 mg

Serious events: 6 serious events

Other events: 38 other events

Deaths: 0 deaths

HAART: Daclatasvir, 30 mg + 60 mg

Serious events: 6 serious events

Other events: 100 other events

Deaths: 0 deaths

Non-HAART Therapy: Daclatasvir, 60 mg

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Highly Active Anti-Retroviral Therapy (HAART):Daclatasvir,30mg n=132 participants at risk Participants taking HIV ritonavir-boosted protease inhibitors received daclatasvir tablets, 30 mg, orally once daily; peg-interferon alfa-2a (pegIFNalfa-2a) solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets, orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART Therapy: Daclatasvir, 60 mg n=39 participants at risk Participants taking other HAART, including rilpivirine, received daclatasvir tablets, 60 mg, orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously once weekly; and ribavirin tablets orally twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	HAART: Daclatasvir, 30 mg + 60 mg n=106 participants at risk Participants taking non-nucleoside reverse transcriptase inhibitors, except rilpivirine, received 2 daclatasvir tablets (1x30 mg and 1x60 mg), orally once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally twice daily for a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at Weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.	Non-HAART Therapy: Daclatasvir, 60 mg n=24 participants at risk Participants not receiving HAART received daclatasvir tablets, 60 mg, orally, once daily; pegIFNalfa-2a solution for injection, 180 µg, subcutaneously, once weekly; and ribavirin tablets, orally, twice daily with a total dose of 1000 mg for participants weighing \<75 kg and 1200 mg for those weighing ≥75 kg, for up to 24 weeks. Participants without virologic response at weeks 4 and 12 continued to receive pegIFNalfa-2a and ribavirin for a total duration of 48 weeks.
Infections and infestations Cellulitis	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Hepatobiliary disorders Cholecystitis	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Gastrointestinal disorders Gastritis	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Gastrointestinal disorders Pancreatitis acute	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Gastrointestinal disorders Diarrhoea	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Gastrointestinal disorders Nausea	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Cardiac disorders Angina pectoris	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Infections and infestations Appendicitis	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Infections and infestations Bronchitis bacterial	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.94% 1/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Psychiatric disorders Depression	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Injury, poisoning and procedural complications Laceration	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Infections and infestations Pneumonia	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.94% 1/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Infections and infestations Staphylococcal bacteraemia	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Vascular disorders Venous thrombosis	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.94% 1/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Psychiatric disorders Mental status changes	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Blood and lymphatic system disorders Pancytopenia	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Renal and urinary disorders Renal failure acute	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Infections and infestations Sepsis	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Metabolism and nutrition disorders Hyperkalaemia	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Respiratory, thoracic and mediastinal disorders Laryngeal cyst	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Infections and infestations Meningitis	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.94% 1/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Cardiac disorders Prinzmetal angina	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.94% 1/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Gastrointestinal disorders Abdominal pain	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Blood and lymphatic system disorders Anaemia	1.5% 2/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.94% 1/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Cardiac disorders Cardiac failure congestive	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Nervous system disorders Dizziness	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Metabolism and nutrition disorders Hypokalaemia	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Metabolism and nutrition disorders Hyponatraemia	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.94% 1/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Ear and labyrinth disorders Sudden hearing loss	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Infections and infestations Thrombophlebitis septic	0.76% 1/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period
Gastrointestinal disorders Vomiting	0.00% 0/132 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	2.6% 1/39 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/106 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period	0.00% 0/24 • From Day 1 to 7 days post last dose of study treatment (up to Week 48) On-treatment period