Trial Outcomes & Findings for A Clinical Trial Comparing the Tolerability of Etravirine to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Treatment-naive HIV-1 Infected Patients (NCT NCT00903682)

Last Updated: 2013-01-14

Results Overview

Proportion of patients with at least 1 treatment-emergent Grade 1-4 Central Nervous System or psychiatric Adverse Event, observed between Baseline through Week 12 and judged by investigator to be at least possibly related to the study drug in ETR group versus EFV group. All Adverse Events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events ("DAIDS AE grading table"). Grade 1-4 covers all severities.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

157 participants

Primary outcome timeframe

between baseline and 12 weeks

Results posted on

2013-01-14

Participant Flow

Participant milestones

Participant milestones
Measure	Etravirine Etravirine (ETR TMC125) 400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks	Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Study STARTED	79	78
Overall Study COMPLETED	63	63
Overall Study NOT COMPLETED	16	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Etravirine Etravirine (ETR TMC125) 400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks	Efavirenz Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Overall Study Adverse Event	6	13
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	5	0
Overall Study Pregnancy	0	1
Overall Study Subject Reached A Virologic Endpoint	1	1
Overall Study Subject Non-Compliant	1	0
Overall Study Patient Couldn't Come For The Visit Due	1	0
Overall Study For Resistent Profile (Excl Crit 2 Met)	1	0

Baseline Characteristics

A Clinical Trial Comparing the Tolerability of Etravirine to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Treatment-naive HIV-1 Infected Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Etravirine n=79 Participants ETR 400mg once daily (4x100mg tablet) + 2 NRTIs + 1 EFV placebo tablet for 48 weeks	Efavirenz n=78 Participants EFV 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks	Total n=157 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	78 Participants n=5 Participants	77 Participants n=7 Participants	155 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age Continuous	37.7 years STANDARD_DEVIATION 9.52 • n=5 Participants	37.6 years STANDARD_DEVIATION 9.82 • n=7 Participants	37.6 years STANDARD_DEVIATION 9.64 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	67 Participants n=5 Participants	60 Participants n=7 Participants	127 Participants n=5 Participants
Region of Enrollment Austria	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment Denmark	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment France	9 participants n=5 Participants	9 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Germany	16 participants n=5 Participants	13 participants n=7 Participants	29 participants n=5 Participants
Region of Enrollment Hungary	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Israel	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Italy	9 participants n=5 Participants	6 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Romania	6 participants n=5 Participants	10 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Russia	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Spain	12 participants n=5 Participants	9 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Switzerland	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment UK	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: between baseline and 12 weeks

Population: The intent-to-treat (ITT) population has been defined as the set of all patients who were randomized and who have taken at least one dose of trial medication, regardless of their compliance with the protocol.

Outcome measures

Outcome measures
Measure	Etravirine n=79 Participants Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks	Efavirenz n=78 Participants Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event	16.5 percentage of patients	46.2 percentage of patients

SECONDARY outcome

Timeframe: between baseline and week 48

Population: ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

The proportion of patients with confirmed plasma viral load \<50 copies/mL at Week 48 as assessed by Time to Loss of Virologic Response (TLOVR)

Outcome measures

Outcome measures
Measure	Etravirine n=79 Participants Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks	Efavirenz n=78 Participants Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Antiviral Activity of ETR vs. EFV	60 Number of participants	58 Number of participants

SECONDARY outcome

Timeframe: between baseline and week 48

Population: ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

The proportion of patients with confirmed plasma viral load \<200 copies/mL at Week 48 as assessed by Time to Loss of Virologic Response (TLOVR)

Outcome measures

Outcome measures
Measure	Etravirine n=79 Participants Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks	Efavirenz n=78 Participants Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Antiviral Activity of ETR vs. EFV	64 Number of participants	62 Number of participants

SECONDARY outcome

Timeframe: between baseline and week 48

Population: ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

The HIV Patient Symptoms Profile measures the tolerability of HIV treatment from the patient's perspective, using 14 concept scales in maximum 84 questions. The response options include a "no" or "yes" answer to "Did symptom occur?". If "yes", there is a problem scale which ranges from 1 = "I had this symptom and it was not a problem" to 5 = "I had this symptom and it was a severe problem". A neuropsychiatric tolerability score is composed as the sum of 21 items and ranges from 0 (best) to 105 (worse). A total Tolerability score (ie, the sum of all items) ranges from 0 (best) to 420 (worse)

Outcome measures

Outcome measures
Measure	Etravirine n=75 Participants Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks	Efavirenz n=74 Participants Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score Total Tolerability Score	-0.04 points on a scale Standard Error 0.03	-0.01 points on a scale Standard Error 0.04
Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score Neuropsychiatric Tolerability Score	-0.04 points on a scale Standard Error 0.06	-0.07 points on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: from baseline to week 48

Population: ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol.

The percentage of patients with at least 1 treatment emergent Grade 1 -4 neurologic or psychiatric adverse event, judged by the investigator to be at least possibly related to the study drug.

Outcome measures

Outcome measures
Measure	Etravirine n=79 Participants Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks	Efavirenz n=78 Participants Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Neuropsychiatric Adverse Events by Week 48	20.3 percentage of patients	52.6 percentage of patients

SECONDARY outcome

Timeframe: at baseline and week 2, 6, 12, 24, 36 and 48

Population: ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol

The mean change in CD4+ cell count from baseline was calculated with a last observation carried forward method; i.e. the last observed value was carried forward, irrespective of the reason for discontinuation.

Outcome measures

Outcome measures
Measure	Etravirine n=74 Participants Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks	Efavirenz n=74 Participants Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Mean Change From Baseline in CD4+ Cell Count Week 48	205.11 number of cells/L (x10^6) Standard Error 20.07	221.39 number of cells/L (x10^6) Standard Error 18.31
Mean Change From Baseline in CD4+ Cell Count Week 24	182.01 number of cells/L (x10^6) Standard Error 16.48	174.08 number of cells/L (x10^6) Standard Error 14.85
Mean Change From Baseline in CD4+ Cell Count Week 36	213.45 number of cells/L (x10^6) Standard Error 19.11	180.18 number of cells/L (x10^6) Standard Error 15.12
Mean Change From Baseline in CD4+ Cell Count Week 2	69.96 number of cells/L (x10^6) Standard Error 9.82	72.45 number of cells/L (x10^6) Standard Error 11.33
Mean Change From Baseline in CD4+ Cell Count Week 6	128.14 number of cells/L (x10^6) Standard Error 13.19	121.62 number of cells/L (x10^6) Standard Error 13.96
Mean Change From Baseline in CD4+ Cell Count Week 12	143.24 number of cells/L (x10^6) Standard Error 13.56	151.46 number of cells/L (x10^6) Standard Error 16.68

SECONDARY outcome

Timeframe: at baseline and all subsequent visits until week 48 in case if virologic failure

Population: ITT: the set of all randomized patients who have taken at least 1 dose of trial medication, regardless of their compliance with the protocol

The evolution of viral genotype and phenotype was assessed by the number of patients with resistance-associated mutations emerging at the endpoint. A mutation was considered emerging if it was present at endpoint and not present at baseline or any pre-baseline assessment. (NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; RAM = resistance-associated mutation, IAS-USA = International AIDS Society - USA)

Outcome measures

Outcome measures
Measure	Etravirine n=79 Participants Etravirine (ETR, TMC125) 400mg once daily (4x100mg tablet) + 2 non-nucleoside reverse transcriptase inhibitors (NRTIs) + 1 Efavirenz (EFV) placebo tablet for 48 weeks	Efavirenz n=78 Participants Efavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Resistance Determinations >= 1 successful genotype after baseline	11 number of participants	9 number of participants
Resistance Determinations >= 1 IAS-USA NRTI RAMs	0 number of participants	2 number of participants
Resistance Determinations >= 1 NRTI Surveillance Drug Resistance Mutation	0 number of participants	2 number of participants
Resistance Determinations >= 1 NNRTI RAMs	2 number of participants	3 number of participants
Resistance Determinations no NRTI or NNRTI RAMs	9 number of participants	6 number of participants

Adverse Events

Etravirine

Serious events: 11 serious events

Other events: 54 other events

Deaths: 0 deaths

Efavirenz

Serious events: 6 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

EMEA Medical Affairs Director Virology

Janssen-Cilag EMEA

Phone: +31 6 542 454 37

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the Sponsor for review at least 60 days prior to submission for publication or presentation. No paper that incorporates Confidential Information will be submitted for publication without Sponsor's prior written consent. If requested in writing, such publication will be withheld for up to an additional 60 calendar days. A publication from the individual Study site data will not be published until the combined results have been published.
Publication restrictions are in place

Restriction type: OTHER

Measure	Etravirine n=79 participants at risk ETR 400mg once daily (4x100mg tablet) + 2 NRTIs + 1 EFV placebo tablet for 48 weeks	Efavirenz n=78 participants at risk EFV 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Blood and lymphatic system disorders Anaemia	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Eye disorders Conjunctivitis	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
General disorders Pyrexia	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Hepatobiliary disorders Cholelithiasis	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Pneumonia	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Pulmonary Tuberculosis	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's Lymphoma	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Skin and subcutaneous tissue disorders Rash	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Gastrointestinal disorders Anal Fissure	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Gastrointestinal disorders Stomatitis	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Anal Abscess	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Anogenital Warts	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Secondary Syphilis	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Investigations Alanine Aminotransferase Increased	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Investigations Aspartate Aminotransferase Increased	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Musculoskeletal and connective tissue disorders Joint Ankylosis	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign Ovarian Tumour	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Renal and urinary disorders Urethral Stenosis	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Respiratory, thoracic and mediastinal disorders Laryngeal Inflammation	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	0.00% 0/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Surgical and medical procedures Abortion Induced	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.

Measure	Etravirine n=79 participants at risk ETR 400mg once daily (4x100mg tablet) + 2 NRTIs + 1 EFV placebo tablet for 48 weeks	Efavirenz n=78 participants at risk EFV 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Ear and labyrinth disorders Vertigo	2.5% 2/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	5.1% 4/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Gastrointestinal disorders Diarrhoea	10.1% 8/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	11.5% 9/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Gastrointestinal disorders Nausea	8.9% 7/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	16.7% 13/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Gastrointestinal disorders Vomiting	2.5% 2/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	7.7% 6/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
General disorders Asthenia	3.8% 3/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	6.4% 5/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
General disorders Pyrexia	6.3% 5/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	6.4% 5/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Influenza	7.6% 6/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	1.3% 1/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Nasopharyngitis	21.5% 17/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	7.7% 6/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Metabolism and nutrition disorders Hypercholesterolaemia	3.8% 3/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	9.0% 7/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Nervous system disorders Dizziness	3.8% 3/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	21.8% 17/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Nervous system disorders Headache	16.5% 13/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	14.1% 11/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Nervous system disorders Somnolence	2.5% 2/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	6.4% 5/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Psychiatric disorders Abnormal Dreams	2.5% 2/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	11.5% 9/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Psychiatric disorders Insomnia	2.5% 2/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	10.3% 8/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Psychiatric disorders Nightmare	3.8% 3/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	9.0% 7/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Psychiatric disorders Sleep Disorder	5.1% 4/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	10.3% 8/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Skin and subcutaneous tissue disorders Pruritus	6.3% 5/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	9.0% 7/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Blood and lymphatic system disorders Anaemia	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	5.1% 4/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Gastrointestinal disorders Dyspepsia	7.6% 6/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	3.8% 3/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
General disorders Fatigue	6.3% 5/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	7.7% 6/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Bronchitis	6.3% 5/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	6.4% 5/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Infections and infestations Pharyngitis	5.1% 4/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	2.6% 2/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Metabolism and nutrition disorders Hypertriglyceridaemia	2.5% 2/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	5.1% 4/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Musculoskeletal and connective tissue disorders Back Pain	8.9% 7/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	3.8% 3/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Nervous system disorders Disturbance in Attention	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	5.1% 4/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Psychiatric disorders Anxiety	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	5.1% 4/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Psychiatric disorders Depression	1.3% 1/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	6.4% 5/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Skin and subcutaneous tissue disorders Rash	6.3% 5/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	2.6% 2/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.
Vascular disorders Hot Flush	0.00% 0/79 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.	5.1% 4/78 • Adverse events represented here were collected between signing of informed consent and the visit at week 48.