Trial Outcomes & Findings for Efficacy and Safety of Telbivudine in Treatment naïve Patients With Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) (NCT NCT00412750)

Last Updated: 2011-07-13

Results Overview

The original primary efficacy variable was the percentage of patients achieving HBV DNA non-detectability utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

159 participants

Primary outcome timeframe

At week 52

Results posted on

2011-07-13

Participant Flow

This is a randomized, open-label, controlled, multi-center two-year study enrolling male and female subjects starting December 2006 and ending February 2009.

Participant milestones

Participant milestones
Measure	LdT + PEG-INF Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	LdT Monotherapy Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.	PEG-INF Monotherapy Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Overall Study STARTED	50	55	54
Overall Study COMPLETED	19	34	31
Overall Study NOT COMPLETED	31	21	23

Reasons for withdrawal

Reasons for withdrawal
Measure	LdT + PEG-INF Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	LdT Monotherapy Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.	PEG-INF Monotherapy Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Overall Study Abnormal laboratory value(s)	1	0	0
Overall Study Administrative problems	21	17	14
Overall Study Adverse Event	8	3	3
Overall Study Lost to Follow-up	1	0	1
Overall Study Withdrawal by Subject	0	1	2
Overall Study Lack of Efficacy	0	0	3

Baseline Characteristics

Efficacy and Safety of Telbivudine in Treatment naïve Patients With Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LdT + PEG-INF n=50 Participants Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	LdT Monotherapy n=55 Participants Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.	PEG-INF Monotherapy n=54 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.	Total n=159 Participants Total of all reporting groups
Age Continuous	35.6 years STANDARD_DEVIATION 10.00 • n=93 Participants	35.0 years STANDARD_DEVIATION 11.48 • n=4 Participants	33.8 years STANDARD_DEVIATION 9.47 • n=27 Participants	34.7 years STANDARD_DEVIATION 10.33 • n=483 Participants
Sex: Female, Male Female	16 Participants n=93 Participants	15 Participants n=4 Participants	20 Participants n=27 Participants	51 Participants n=483 Participants
Sex: Female, Male Male	34 Participants n=93 Participants	40 Participants n=4 Participants	34 Participants n=27 Participants	108 Participants n=483 Participants

PRIMARY outcome

Timeframe: At week 52

Population: The analysis was planned on intention to treat (ITT) population. Due to premature study termination, the analysis was not performed.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Weeks 12 and 24

Population: Intent to Treat (ITT) population. The study was terminated and some participants did not complete all visits. "n" in each of the categories represents the number of participants in each arm with non-missing efficacy endpoint observations for the respective week.

The percentage of participants who achieved HBV DNA non-detectability using the COBAS Amplicor HBV Monitor assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL) and Alanine aminotransferase (ALT) normalization defined as ALT within normal limits on two successive visits for a patient with an elevated ALT (\>1.0 x upper limit normal) at baseline summarized at Weeks 12 and 24.

Outcome measures

Outcome measures
Measure	LdT + PEG-INF n=49 Participants Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB) ALT normalization Week 12 (n=37,52,50)	13.5 Percentage of participants	28.8 Percentage of participants	20.0 Percentage of participants
Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB) HBV DNA non-detectability Week 12 (n=37,52,50)	13.5 Percentage of participants	9.6 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB) HBV DNA non-detectability Week 24 (n=17,48,42)	70.6 Percentage of participants	35.4 Percentage of participants	7.1 Percentage of participants
Percentage of Participants With HBV DNA Non-detectability and Alanine Aminotransferase (ALT) Normalization at Week 12 and Week 24 in Participants With HBeAg-positive Chronic Hepatitis B (CHB) ALT normalization Week 24 (n=17,48,41)	11.8 Percentage of participants	54.2 Percentage of participants	31.7 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 12 and 24

Population: Intent to Treat (ITT) population. n= the number of patients who have both baseline and post baseline observation for the respective week

The change from baseline in HBV DNA concentration at Weeks 12 and 24 was analyzed using an analysis of covariance (ANCOVA) model with baseline HBV DNA concentration (log10 copies/ml) as a covariate, treatment and country as factors.

Outcome measures

Outcome measures
Measure	LdT + PEG-INF n=49 Participants Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Change From Baseline in HBV DNA Concentration Week 12 (n= 37, 52, 50)	-6.0569 log 10 copies/ml Standard Error 0.3124	-5.1658 log 10 copies/ml Standard Error 0.2717	-1.8991 log 10 copies/ml Standard Error 0.2607
Change From Baseline in HBV DNA Concentration Week 24 (n= 17, 48, 42)	-6.9187 log 10 copies/ml Standard Error 0.5462	-5.9633 log 10 copies/ml Standard Error 0.3523	-2.4513 log 10 copies/ml Standard Error 0.3485

SECONDARY outcome

Timeframe: Weeks 48 and 52

Population: Intent to treat (ITT) population. As most patients did not reach Week 48 and Week 52, the LOCF was used.

The percentage of participants with Virologic breakthrough at Week 48 and 52 by treatment. For the subgroup of patients on treatment who achieve HBV DNA \>= 1 log10 copies/mL reduction from baseline on 2 consecutive visits, Virologic Breakthrough is defined as HBV DNA \>= 1 log10 copies/mL from nadir on two consecutive visits.

Outcome measures

Outcome measures
Measure	LdT + PEG-INF n=49 Participants Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52 Virologic breakthrough Week 48	0.0 Percentage of participants	5.7 Percentage of participants	7.5 Percentage of participants
Percentage of Participants Who Experienced Virologic Breakthrough at Weeks 48 and 52 Virologic breakthrough Week 52	0.0 Percentage of participants	7.5 Percentage of participants	9.4 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 18, 24, 48, 52 and Treatment completion (TC)

HBeAg loss is defined as the loss of detectable serum HBeAg in a patient who was HBeAg positive at baseline. HBeAg seroconversion is defined as HBeAg loss with detectable Hepatitis B 'e' antibody (HBeAb). The efficacy was assessed for 18 weeks, 24 weeks, 48 weeks, 52 weeks and on treatment completion (TC).

Outcome measures

Outcome measures
Measure	LdT + PEG-INF n=49 Participants Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.	PEG-INF Monotherapy n=53 Participants Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg loss Week 18 (n=28,51,45)	17.9 Percentage of participants	7.8 Percentage of participants	8.9 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg seroconversion Week 18 (n=28,51,45)	17.9 Percentage of participants	7.8 Percentage of participants	8.9 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg loss Week 24 (n=17,48,42)	17.6 Percentage of participants	6.3 Percentage of participants	11.9 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg seroconversion Week 24 (n=17,48,42)	7.6 Percentage of participants	4.2 Percentage of participants	11.9 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg loss Week 48 (n=0,19,12)	NA Percentage of participants Participants in the LdT + PEG-INF arm were discontinued prior to week 48, hence no data is available	36.8 Percentage of participants	25.0 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg seroconversion Week 48 (n=0,19,12)	NA Percentage of participants Participants in the LdT + PEG-INF arm were discontinued prior to week 48, hence no data is available	36.8 Percentage of participants	25.0 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg loss Week 52 (n=0,10,6)	NA Percentage of participants Participants in the LdT + PEG-INF arm were discontinued prior to week 48, hence no data is available	50.0 Percentage of participants	16.7 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg seroconversion Week 52 (n=0,10,6)	NA Percentage of participants Participants in the LdT + PEG-INF arm were discontinued prior to week 48, hence no data is available	50.0 Percentage of participants	16.7 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg loss TC (n=14,24,9)	7.1 Percentage of participants	29.2 Percentage of participants	33.3 Percentage of participants
Percentage of Participants With Hepatitis B 'e' Antigen (HBeAg) Loss and HBeAg Seroconversion HBeAg seroconversion TC (n=14,24,9)	7.1 Percentage of participants	25.0 Percentage of participants	33.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: The analysis was planned on intent to treat (ITT) population. Due to premature study termination, the analysis was not performed.

Antiviral efficacy was assessed by percentage of patients achieving HBV DNA non-detectability assay utilizing polymerase chain reaction (PCR) (threshold for detection 300 copies/mL); however, this analysis was not performed due to premature study termination.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 52

Population: The analysis was planned on intent to treat (ITT) population. Due to premature study termination, the analysis was not performed.

Outcome measures

Outcome data not reported

Adverse Events

LdT + PEG-INF

Serious events: 11 serious events

Other events: 38 other events

Deaths: 0 deaths

LdT Monotherapy

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

PEG-INF Monotherapy

Serious events: 2 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	LdT + PEG-INF n=50 participants at risk Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	LdT Monotherapy n=54 participants at risk Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.	PEG-INF Monotherapy n=54 participants at risk Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Congenital, familial and genetic disorders Mitochondrial myopathy	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Chest pain	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Pyrexia	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Hepatobiliary disorders Hepatitis	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Infections and infestations Appendicitis	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Infections and infestations Urinary tract infection	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Investigations Blood creatine phosphokinase increased	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Musculoskeletal and connective tissue disorders Myopathy	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Dysaesthesia	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Hypoaesthesia	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Neuropathy peripheral	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Paraesthesia	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Peripheral sensory neuropathy	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Polyneuropathy	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Psychiatric disorders Depression suicidal	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.

Measure	LdT + PEG-INF n=50 participants at risk Telbivudine (LdT) 600 mg orally once a day for 104 weeks in combination with peg interferon (PEG-INF) alpha-2a 180 μg subcutaneous injection once a week for 52 weeks.	LdT Monotherapy n=54 participants at risk Telbivudine (LdT) monotherapy: 600 mg orally once daily for 104 weeks.	PEG-INF Monotherapy n=54 participants at risk Peg interferon (PEG- INF) alpha-2a monotherapy: 180 μg subcutaneous injection once a week for 52 weeks.
Blood and lymphatic system disorders Leukopenia	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	9.3% 5/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Blood and lymphatic system disorders Neutropenia	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Blood and lymphatic system disorders Thrombocytopenia	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Ear and labyrinth disorders Tinnitus	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Gastrointestinal disorders Abdominal distension	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Gastrointestinal disorders Abdominal pain	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Gastrointestinal disorders Abdominal pain upper	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Gastrointestinal disorders Diarrhoea	12.0% 6/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Gastrointestinal disorders Dry mouth	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Gastrointestinal disorders Nausea	20.0% 10/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	16.7% 9/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Gastrointestinal disorders Vomiting	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Asthenia	16.0% 8/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	11.1% 6/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	18.5% 10/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Fatigue	16.0% 8/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	13.0% 7/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Influenza like illness	16.0% 8/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	22.2% 12/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Irritability	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Pain	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
General disorders Pyrexia	22.0% 11/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	24.1% 13/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Infections and infestations Influenza	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	9.3% 5/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Infections and infestations Nasopharyngitis	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Infections and infestations Sinusitis	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Infections and infestations Upper respiratory tract infection	8.0% 4/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	20.4% 11/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	18.5% 10/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Investigations Blood creatine phosphokinase increased	8.0% 4/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Investigations Neutrophil count decreased	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Investigations Weight decreased	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Metabolism and nutrition disorders Anorexia	10.0% 5/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Metabolism and nutrition disorders Decreased appetite	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Musculoskeletal and connective tissue disorders Arthralgia	18.0% 9/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Musculoskeletal and connective tissue disorders Myalgia	28.0% 14/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	9.3% 5/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	16.7% 9/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	4.0% 2/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Headache	16.0% 8/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	16.7% 9/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	31.5% 17/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Lethargy	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Nervous system disorders Paraesthesia	12.0% 6/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Psychiatric disorders Anxiety	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Psychiatric disorders Depression	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	9.3% 5/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Psychiatric disorders Insomnia	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	16.7% 9/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Respiratory, thoracic and mediastinal disorders Cough	20.0% 10/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.0% 3/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	1.9% 1/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Skin and subcutaneous tissue disorders Alopecia	12.0% 6/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	27.8% 15/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Skin and subcutaneous tissue disorders Dry skin	2.0% 1/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	0.00% 0/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Skin and subcutaneous tissue disorders Pruritus	10.0% 5/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	5.6% 3/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	16.7% 9/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/50 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	3.7% 2/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.	7.4% 4/54 Safety Population defined as all patients who received one dose of study drug and had at least one post baseline assessment.