Trial Outcomes & Findings for HELPS Study - A Study of Peginterferon Alfa-2a (Pegasys) in Patients With Chronic Hepatitis C (CHC) and End-Stage Renal Disease (ESRD) (NCT NCT02806505)

Last Updated: 2016-10-31

Results Overview

SVR was defined as the percentage of patients with undetectable HCV RNA. SVR rate was calculated as the number of participants with an undetectable HCV RNA divided by the number of participants of the respective participant population. The last single HCV RNA less than (\<) 50 international units per millilitre (IU/mL) measured \>=140 days after treatment end (i.e., \>= 20 weeks after treatment end) was used to determine SVR. Participants without measurements in this time window were considered to be nonresponders.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

81 participants

Primary outcome timeframe

24 weeks after end of treatment (Week 72)

Results posted on

2016-10-31

Participant Flow

A total of 85 participants were randomly assigned to the two treatment groups (Peginterferon alfa-2a 135 mcg/week and Peginterferon alfa-2a 90 mcg/week). A total of 4 randomized participants did not receive any study drug.

Participant milestones

Participant milestones
Measure	Peginterferon Alfa-2a 135 Microgram (mcg) Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.
Overall Study STARTED	38	43
Overall Study COMPLETED	28	32
Overall Study NOT COMPLETED	10	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Peginterferon Alfa-2a 135 Microgram (mcg) Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.
Overall Study Adverse event/intercurrent illness	1	3
Overall Study Death	4	0
Overall Study Did not cooperate/refused treatment	3	3
Overall Study Failure to return	0	1
Overall Study Insufficient therapeutic response	2	4

Baseline Characteristics

HELPS Study - A Study of Peginterferon Alfa-2a (Pegasys) in Patients With Chronic Hepatitis C (CHC) and End-Stage Renal Disease (ESRD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peginterferon Alfa-2a 135 Microgram (mcg) n=38 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg n=43 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.	Total n=81 Participants Total of all reporting groups
Age, Continuous	44.2 years STANDARD_DEVIATION 11.26 • n=5 Participants	42.9 years STANDARD_DEVIATION 11.26 • n=7 Participants	43.5 years STANDARD_DEVIATION 11.21 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	34 Participants n=7 Participants	57 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks after end of treatment (Week 72)

Population: The ITT analysis population included all the randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a 135 Microgram (mcg) n=38 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg n=43 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.
Percentage of Participants With Sustained Virological Response (SVR) at 24 Weeks After End of Treatment	39.5 percentage of participants Interval 24.0 to 56.6	34.9 percentage of participants Interval 21.0 to 50.9

SECONDARY outcome

Timeframe: EOT (Week 48)

Population: The ITT analysis population included all the randomized participants who received at least one dose of study treatment.

Virological response at the end of study treatment was defined as the percentage of participants with undetectable HCV RNA. This response rate at end of treatment was calculated as the number of participants with undetectable HCV RNA divided by the number of participants of the respective participant population.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a 135 Microgram (mcg) n=38 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg n=43 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.
Percentage of Participants With Virological Response (Non-detectable Hepatitis C Virus-ribonucleic Acid [HCV RNA]) at End of Treatment (EOT)	57.9 percentage of participants Interval 40.8 to 73.7	48.8 percentage of participants Interval 33.3 to 64.5

SECONDARY outcome

Timeframe: Weeks 12 and 24

Population: The ITT analysis population included all the randomized participants who received at least one dose of study treatment.

Virological response at Weeks 12 and 24 was computed as the percentage of participants with at least a 2-log 10 decrease in HCV RNA at Weeks 12 and 24 as compared with baseline or with an unquantifiable (\< 600 IU/mL) or an undetectable HCV RNA test result (\< 50 IU/mL) at Week 12 and at Week 24, calculated as the number of participants meeting this criterion divided by the number of participants of the respective participant population.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a 135 Microgram (mcg) n=38 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg n=43 Participants Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.
Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24 Week 12	71.1 percentage of participants Interval 54.1 to 84.6	69.8 percentage of participants Interval 53.9 to 82.8
Percentage of Participants With Virological Response (at Least a 2-log 10 Decrease in HCV RNA as Compared With Baseline or Unquantifiable [Less Than {<} 600 International Unit/Milliliter {IU/mL}] or Undetectable HCV RNA [< 50 IU/mL]) at Week 12 and 24 Week 24	65.8 percentage of participants Interval 48.6 to 80.4	72.1 percentage of participants Interval 56.3 to 84.7

Adverse Events

Peginterferon Alfa-2a 135 Microgram (mcg)

Serious events: 14 serious events

Other events: 30 other events

Deaths: 0 deaths

Peginterferon Alfa-2a 90 mcg

Serious events: 14 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Peginterferon Alfa-2a 135 Microgram (mcg) n=38 participants at risk Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg n=43 participants at risk Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.
Infections and infestations Pneumonia	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	4.7% 2/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Infections and infestations Sepsis	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Infections and infestations Arthritis bacterial	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Infections and infestations Bacterial infection	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Infections and infestations Endocarditis	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Infections and infestations Urinary tract infection	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Infections and infestations Viral infection	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Cardiac disorders Coronary artery disease	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Cardiac disorders Acute coronary syndrome	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Cardiac disorders Cardiac failure	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Cardiac disorders Coronary artery stenosis	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Cardiac disorders Hypertrophic cardiomyopathy	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Nervous system disorders Complex regional pain syndrome	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Nervous system disorders Grand mal convulsion	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Nervous system disorders Haemorrhagic stroke	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Injury, poisoning and procedural complications Poisoning	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Endocrine disorders Hyperparathyroidism secondary	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	4.7% 2/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Chest pain	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Multi-organ failure	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Musculoskeletal and connective tissue disorders Fibromyalgia	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Psychiatric disorders Confusional state	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Psychiatric disorders Major depression	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Blood and lymphatic system disorders Anaemia	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Congenital, familial and genetic disorders Gene mutation	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Gastrointestinal disorders Abdominal pain	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Immune system disorders Transplant rejection	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Investigations Medical observation	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Renal and urinary disorders Haematuria	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Reproductive system and breast disorders Metrorrhagia	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Cardiac disorders Ventricle rupture	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.

Measure	Peginterferon Alfa-2a 135 Microgram (mcg) n=38 participants at risk Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 135 mcg subcutaneously (SC) once weekly up to Week 48.	Peginterferon Alfa-2a 90 mcg n=43 participants at risk Chronic Hepatitis C participants with end-stage renal disease undergoing hemodialysis will receive Peginterferon alfa-2a 90 mcg SC once weekly up to Week 48.
Blood and lymphatic system disorders Anaemia	36.8% 14/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	32.6% 14/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Endocrine disorders Hyperparathyroidism secondary	10.5% 4/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	14.0% 6/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Endocrine disorders Hypothyroidism	10.5% 4/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Eye disorders Conjunctivitis	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	7.0% 3/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Eye disorders Eye pain	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Gastrointestinal disorders Constipation	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Gastrointestinal disorders Diarrhoea	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	9.3% 4/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Gastrointestinal disorders Dyspepsia	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	4.7% 2/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Gastrointestinal disorders Nausea	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Gastrointestinal disorders Vomiting	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Asthenia	18.4% 7/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	16.3% 7/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Chills	7.9% 3/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Fatigue	15.8% 6/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	16.3% 7/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Influenza like illness	15.8% 6/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	14.0% 6/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Malaise	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
General disorders Pyrexia	13.2% 5/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	16.3% 7/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Infections and infestations Oral herpes	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Metabolism and nutrition disorders Anorexia	7.9% 3/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	7.0% 3/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	7.0% 3/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Musculoskeletal and connective tissue disorders Arthralgia	13.2% 5/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Musculoskeletal and connective tissue disorders Myalgia	18.4% 7/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	18.6% 8/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Musculoskeletal and connective tissue disorders Pain in extremity	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	7.0% 3/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Nervous system disorders Dizziness	7.9% 3/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	4.7% 2/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Nervous system disorders Headache	23.7% 9/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	30.2% 13/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Psychiatric disorders Depression	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	9.3% 4/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Psychiatric disorders Insomnia	10.5% 4/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	7.0% 3/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Respiratory, thoracic and mediastinal disorders Cough	7.9% 3/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	4.7% 2/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	2.3% 1/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Skin and subcutaneous tissue disorders Alopecia	2.6% 1/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	9.3% 4/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Skin and subcutaneous tissue disorders Dry skin	5.3% 2/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	0.00% 0/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Skin and subcutaneous tissue disorders Pruritus	7.9% 3/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	4.7% 2/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.
Vascular disorders Hypertension	13.2% 5/38 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.	32.6% 14/43 • Baseline up to follow up period (Week 72) An adverse event was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started.