EARLiMS: Efficacy of Fingolimod in de Novo Patients Versus Fingolimod in Patients Previously Treated With a First Line Disease Modifying Therapy
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01498887
Collaborator
(none)
347
47
2
48.1
7.4
0.2
Study Details
Study Description
Brief Summary
This study assessed the efficacy of fingolimod in patients with short duration relapsing-remitting multiple sclerosis who had not been previously treated with disease-modifying therapies (DMTs), versus patients with the same disease duration who had previously received first-line DMTs.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
347 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multi-centre, Open-label, Non-randomised, Parallel Group Clinical Trial to Assess the Efficacy of Fingolimod in Naive Patients Versus Fingolimod in Patients Previously Treated With Interferons or Glatiramer Acetate, Based on the Presence of Relapses in Patients With Relapsing-remitting Multiple Sclerosis.
Actual Study Start Date
:
Dec 24, 2011
Actual Primary Completion Date
:
Dec 26, 2015
Actual Study Completion Date
:
Dec 26, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Naive or de novo participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
Drug: Fingolimod (FTY720)
Hard gelatin capsules containing 0.5 mg of fingolimod.
|
| Experimental: Previously treated with first-line DMTs participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
Drug: Fingolimod (FTY720)
Hard gelatin capsules containing 0.5 mg of fingolimod.
|
Outcome Measures
Primary Outcome Measures
- Annual Relapse Rate (ARR) [12 months]
ARR = 365 days * number of relapses / total days taking the study medication.
Secondary Outcome Measures
- Time to First Relapse [first day of treatment to the first day of a new neurological symptom or worsening of an existing one, up to 12 months]
Time to first relapse was defined as the time from the first day of treatment to the first day of a new neurological symptom or worsening of an existing one.
- Change From Baseline in Expanded Disability Status Scale (EDSS) Score [baseline, 12 months]
The EDSS is an ordinal clinical rating scale ranging from a total score of 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. A negative change from baseline indicates improvement.
- Change From Baseline in Cerebral Volume [baseline, 12 months]
Cerebral volume was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement.
- Percentage of Participants With Mild, Moderate or Severe Relapse [12 months]
The investigator classified a relapse as moderate-severe if oral or intravenous (IV) treatment (according to the local clinical practice) with steroids and/or hospitalization was needed. If neither oral nor IV treatment with steroids nor hospitalization was needed, the relapse was considered as mild.
- Percentage of Relapse-free Participants [12 months]
Relapse-free participants were defined as participants who experienced no new neurological symptom or worsening of an existing one (relapses) during the 12-month treatment period with 0.5 mg fingolimod.
- Mean Number of T2 Active Lesions [12 months]
The mean number of new or enlarged T2 active lesions was assessed by MRI.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients diagnosed with multiple sclerosis, according to the 2010 revised McDonald criteria, with a relapsing-remitting course, and with at least 9 T2 lesions consistent with the disease, with disease duration greater than or equal to one year and less than or equal to five years.
-
Patients who have had at least two relapses in the past two years and an Expanded Disability Status Scale score between 0 and 3.5, inclusive.
Patients
-
Treatment naïve: patients who have never been treated with a Disease Modifying Therapy or
-
Previously treated with a first-line Disease Modifying Therapy
Exclusion Criteria:
- Patients who have received treatment with:
Fingolimod at any time (e.g. participation in a fingolimod clinical trial), Immunosuppressant drugs such as azathioprine or methotrexate at any time; Immunoglobulins in the past 6 months. Monoclonal antibodies including natalizumab, Cladribine, cyclophosphamide or mitoxantrone, at any time.
- Other protocol defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | East Gosford | New South Wales | Australia | 2250 |
| 2 | Novartis Investigative Site | Kanwal | New South Wales | Australia | 2259 |
| 3 | Novartis Investigative Site | Liverpool | New South Wales | Australia | 2170 |
| 4 | Novartis Investigative Site | New Lambton Heights | New South Wales | Australia | 2305 |
| 5 | Novartis Investigative Site | Sydney | New South Wales | Australia | 2050 |
| 6 | Novartis Investigative Site | Auchenflower | Queensland | Australia | 4066 |
| 7 | Novartis Investigative Site | Adelaide | South Australia | Australia | |
| 8 | Novartis Investigative Site | Box Hill | Victoria | Australia | 3128 |
| 9 | Novartis Investigative Site | Fitzroy | Victoria | Australia | 3011 |
| 10 | Novartis Investigative Site | Melbourne | Victoria | Australia | 3000 |
| 11 | Novartis Investigative Site | Parkville | Victoria | Australia | 3050 |
| 12 | Novartis Investigative Site | Nedlands | Western Australia | Australia | 6009 |
| 13 | Novartis Investigative Site | Bedford Park | Australia | SA 5042 | |
| 14 | Novartis Investigative Site | Brisbane Queensland | Australia | 4029 | |
| 15 | Novartis Investigative Site | Geelong VIC | Australia | 3220 | |
| 16 | Novartis Investigative Site | Ferrol | A Coruna | Spain | 15405 |
| 17 | Novartis Investigative Site | Córdoba | Andalucia | Spain | 14004 |
| 18 | Novartis Investigative Site | Granada | Andalucia | Spain | 18012 |
| 19 | Novartis Investigative Site | Malaga | Andalucia | Spain | 29010 |
| 20 | Novartis Investigative Site | Sevilla | Andalucia | Spain | 41009 |
| 21 | Novartis Investigative Site | Sevilla | Andalucia | Spain | 41014 |
| 22 | Novartis Investigative Site | Oviedo | Asturias | Spain | 33006 |
| 23 | Novartis Investigative Site | Santander | Cantabria | Spain | 39008 |
| 24 | Novartis Investigative Site | Albacete | Castilla La Mancha | Spain | 02006 |
| 25 | Novartis Investigative Site | Valladolid | Castilla Y Leon | Spain | 47011 |
| 26 | Novartis Investigative Site | Leon | Castilla Y León | Spain | 24080 |
| 27 | Novartis Investigative Site | Badalona | Catalunya | Spain | 08916 |
| 28 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08035 |
| 29 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08036 |
| 30 | Novartis Investigative Site | Tarragona | Cataluña | Spain | 43007 |
| 31 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46010 |
| 32 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46017 |
| 33 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46026 |
| 34 | Novartis Investigative Site | La Coruna | Galicia | Spain | 15006 |
| 35 | Novartis Investigative Site | Palma De Mallorca | Islas Baleares | Spain | 07120 |
| 36 | Novartis Investigative Site | Las Palmas de Gran Canaria | Las Palmas De G.C | Spain | 35010 |
| 37 | Novartis Investigative Site | Pamplona | Navarra | Spain | 31008 |
| 38 | Novartis Investigative Site | Barakaldo | Pais Vasco | Spain | 48903 |
| 39 | Novartis Investigative Site | Bilbao | Pais Vasco | Spain | 48013 |
| 40 | Novartis Investigative Site | Barcelona | Spain | 08041 | |
| 41 | Novartis Investigative Site | Las Palmas de Gran Canaria | Spain | 35016 | |
| 42 | Novartis Investigative Site | Madrid | Spain | 28006 | |
| 43 | Novartis Investigative Site | Madrid | Spain | 28007 | |
| 44 | Novartis Investigative Site | Madrid | Spain | 28034 | |
| 45 | Novartis Investigative Site | Madrid | Spain | 28040 | |
| 46 | Novartis Investigative Site | Madrid | Spain | 28041 | |
| 47 | Novartis Investigative Site | Santa Cruz de Tenerife | Spain | 38009 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01498887
Other Study ID Numbers:
- CFTY720DES03
- 2011-003484-30
First Posted:
Dec 26, 2011
Last Update Posted:
Jan 25, 2019
Last Verified:
Aug 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | This was an open-label, non-randomized, parallel group study. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Period Title: Overall Study | ||
| STARTED | 200 | 147 |
| Safety Set | 200 | 147 |
| Intent-to-treat | 185 | 135 |
| COMPLETED | 184 | 136 |
| NOT COMPLETED | 16 | 11 |
Baseline Characteristics
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants | Total |
|---|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Total of all reporting groups |
| Overall Participants | 185 | 135 | 320 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
33.1
(8.08)
|
34.0
(7.44)
|
33.5
(7.81)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
137
74.1%
|
88
65.2%
|
225
70.3%
|
| Male |
48
25.9%
|
47
34.8%
|
95
29.7%
|
Outcome Measures
| Title | Annual Relapse Rate (ARR) |
|---|---|
| Description | ARR = 365 days * number of relapses / total days taking the study medication. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population was analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Measure Participants | 185 | 135 |
| Mean (Standard Deviation) [Relapses per year] |
0.290
(0.7399)
|
0.354
(0.8547)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Naive or de Novo Participants, Previously Treated With First-line DMTs Participants |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3118 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Time to First Relapse |
|---|---|
| Description | Time to first relapse was defined as the time from the first day of treatment to the first day of a new neurological symptom or worsening of an existing one. |
| Time Frame | first day of treatment to the first day of a new neurological symptom or worsening of an existing one, up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population was analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Measure Participants | 185 | 135 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Change From Baseline in Expanded Disability Status Scale (EDSS) Score |
|---|---|
| Description | The EDSS is an ordinal clinical rating scale ranging from a total score of 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. A negative change from baseline indicates improvement. |
| Time Frame | baseline, 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the ITT population with both baseline and 12 month values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Measure Participants | 182 | 130 |
| Mean (Standard Deviation) [score on a scale] |
0.000
(0.8040)
|
-0.077
(0.7911)
|
| Title | Change From Baseline in Cerebral Volume |
|---|---|
| Description | Cerebral volume was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement. |
| Time Frame | baseline, 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the ITT population with both baseline and 12 month values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Measure Participants | 92 | 43 |
| Mean (95% Confidence Interval) [Percent change] |
-0.595
|
-0.387
|
| Title | Percentage of Participants With Mild, Moderate or Severe Relapse |
|---|---|
| Description | The investigator classified a relapse as moderate-severe if oral or intravenous (IV) treatment (according to the local clinical practice) with steroids and/or hospitalization was needed. If neither oral nor IV treatment with steroids nor hospitalization was needed, the relapse was considered as mild. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only participants from the ITT population with severity values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Measure Participants | 47 | 39 |
| Mild |
42.55
23%
|
38.46
28.5%
|
| Moderate |
57.45
31.1%
|
56.41
41.8%
|
| Severe |
0.00
0%
|
5.13
3.8%
|
| Title | Percentage of Relapse-free Participants |
|---|---|
| Description | Relapse-free participants were defined as participants who experienced no new neurological symptom or worsening of an existing one (relapses) during the 12-month treatment period with 0.5 mg fingolimod. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population was analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Measure Participants | 185 | 135 |
| Number [Percent] |
71.89
|
66.67
|
| Title | Mean Number of T2 Active Lesions |
|---|---|
| Description | The mean number of new or enlarged T2 active lesions was assessed by MRI. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from the ITT population with 12 month T2 lesion numbers were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded. |
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants |
|---|---|---|
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. |
| Measure Participants | 163 | 106 |
| Mean (Standard Deviation) [T2 lesions] |
2.0
(3.36)
|
1.6
(2.72)
|
Adverse Events
| Time Frame | Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants | All Participants | |||
| Arm/Group Description | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | ||||
All Cause Mortality |
||||||
| Naive or de Novo Participants | Previously Treated With First-line DMTs Participants | All Participants | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Naive or de Novo Participants | Previously Treated With First-line DMTs Participants | All Participants | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/200 (5.5%) | 4/147 (2.7%) | 15/347 (4.3%) | |||
| Cardiac disorders | ||||||
| Atrioventricular block | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Atrioventricular block second degree | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Bradycardia | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Sinus bradycardia | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Hepatobiliary disorders | ||||||
| Cholelithiasis | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Hepatitis acute | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Immune system disorders | ||||||
| Drug hypersensitivity | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Infections and infestations | ||||||
| Lower respiratory tract infection | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Diffuse large B-cell lymphoma | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Nervous system disorders | ||||||
| Brain oedema | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Epilepsy | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Multiple sclerosis relapse | 2/200 (1%) | 1/147 (0.7%) | 3/347 (0.9%) | |||
| Partial seizures | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Reproductive system and breast disorders | ||||||
| Ovarian cyst | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Naive or de Novo Participants | Previously Treated With First-line DMTs Participants | All Participants | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 143/200 (71.5%) | 114/147 (77.6%) | 257/347 (74.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 3/200 (1.5%) | 0/147 (0%) | 3/347 (0.9%) | |||
| Iron deficiency anaemia | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Lymphadenitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Lymphadenopathy | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Lymphocytosis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Lymphopenia | 9/200 (4.5%) | 7/147 (4.8%) | 16/347 (4.6%) | |||
| Microcytic anaemia | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Cardiac disorders | ||||||
| Atrioventricular block first degree | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Bradycardia | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Palpitations | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Tachycardia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Congenital, familial and genetic disorders | ||||||
| Retinal anomaly congenital | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Ear and labyrinth disorders | ||||||
| Cerumen impaction | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Ear pain | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Hypoacusis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Tinnitus | 2/200 (1%) | 1/147 (0.7%) | 3/347 (0.9%) | |||
| Vertigo | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Eye disorders | ||||||
| Amblyopia | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Astigmatism | 2/200 (1%) | 1/147 (0.7%) | 3/347 (0.9%) | |||
| Conjunctival haemorrhage | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Conjunctivitis | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Diplopia | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Dry eye | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Erythema of eyelid | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Eye pain | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Eyelid oedema | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Macular oedema | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Myopia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Ocular hyperaemia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Optic atrophy | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Pinguecula | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Presbyopia | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Retinal pigment epitheliopathy | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Strabismus | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Vision blurred | 2/200 (1%) | 3/147 (2%) | 5/347 (1.4%) | |||
| Visual impairment | 2/200 (1%) | 2/147 (1.4%) | 4/347 (1.2%) | |||
| Vitreous floaters | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 3/200 (1.5%) | 1/147 (0.7%) | 4/347 (1.2%) | |||
| Abdominal distension | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Abdominal pain | 1/200 (0.5%) | 2/147 (1.4%) | 3/347 (0.9%) | |||
| Abdominal pain upper | 5/200 (2.5%) | 3/147 (2%) | 8/347 (2.3%) | |||
| Constipation | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Dental caries | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Dental cyst | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Diarrhoea | 5/200 (2.5%) | 9/147 (6.1%) | 14/347 (4%) | |||
| Dyspepsia | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Gastritis | 3/200 (1.5%) | 1/147 (0.7%) | 4/347 (1.2%) | |||
| Gastrointestinal motility disorder | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Gastrooesophageal reflux disease | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Gingival bleeding | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Haemorrhoids | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Hyperchlorhydria | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Mouth ulceration | 4/200 (2%) | 1/147 (0.7%) | 5/347 (1.4%) | |||
| Nausea | 7/200 (3.5%) | 5/147 (3.4%) | 12/347 (3.5%) | |||
| Odynophagia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Oesophagitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Oral discomfort | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Oral pain | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Stomatitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Toothache | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Vomiting | 2/200 (1%) | 4/147 (2.7%) | 6/347 (1.7%) | |||
| General disorders | ||||||
| Adverse drug reaction | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Chest discomfort | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Chest pain | 1/200 (0.5%) | 3/147 (2%) | 4/347 (1.2%) | |||
| Exercise tolerance decreased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Fatigue | 11/200 (5.5%) | 9/147 (6.1%) | 20/347 (5.8%) | |||
| Gait disturbance | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Influenza like illness | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Pain | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Pyrexia | 1/200 (0.5%) | 5/147 (3.4%) | 6/347 (1.7%) | |||
| Hepatobiliary disorders | ||||||
| Biliary colic | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hepatic function abnormal | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Hepatomegaly | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hypertransaminasaemia | 3/200 (1.5%) | 0/147 (0%) | 3/347 (0.9%) | |||
| Immune system disorders | ||||||
| Hypersensitivity | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Infections and infestations | ||||||
| Acute tonsillitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Bacterial vaginosis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Bronchitis | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Conjunctivitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Conjunctivitis viral | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Cystitis | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Ear infection | 1/200 (0.5%) | 2/147 (1.4%) | 3/347 (0.9%) | |||
| Folliculitis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Fungal skin infection | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Gastric infection | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Gastroenteritis | 9/200 (4.5%) | 6/147 (4.1%) | 15/347 (4.3%) | |||
| Gastroenteritis viral | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Genital herpes | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Genitourinary tract infection | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hand-foot-and-mouth disease | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Herpes ophthalmic | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Herpes simplex | 2/200 (1%) | 1/147 (0.7%) | 3/347 (0.9%) | |||
| Herpes zoster | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Influenza | 3/200 (1.5%) | 3/147 (2%) | 6/347 (1.7%) | |||
| Laryngitis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Lower respiratory tract infection | 3/200 (1.5%) | 0/147 (0%) | 3/347 (0.9%) | |||
| Molluscum contagiosum | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Nasopharyngitis | 16/200 (8%) | 8/147 (5.4%) | 24/347 (6.9%) | |||
| Onychomycosis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Ophthalmic herpes zoster | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Oral herpes | 7/200 (3.5%) | 5/147 (3.4%) | 12/347 (3.5%) | |||
| Paronychia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Periodontitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Pertussis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Pharyngitis | 8/200 (4%) | 4/147 (2.7%) | 12/347 (3.5%) | |||
| Pharyngitis bacterial | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Pharyngitis streptococcal | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Pharyngotonsillitis | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Pneumonia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Respiratory tract infection | 4/200 (2%) | 2/147 (1.4%) | 6/347 (1.7%) | |||
| Rhinitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Sinusitis | 3/200 (1.5%) | 2/147 (1.4%) | 5/347 (1.4%) | |||
| Sinusitis bacterial | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Skin infection | 0/200 (0%) | 3/147 (2%) | 3/347 (0.9%) | |||
| Tinea versicolour | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Tonsillitis | 6/200 (3%) | 3/147 (2%) | 9/347 (2.6%) | |||
| Tonsillitis bacterial | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Tooth abscess | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Tooth infection | 1/200 (0.5%) | 2/147 (1.4%) | 3/347 (0.9%) | |||
| Tracheobronchitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Upper respiratory tract infection | 15/200 (7.5%) | 12/147 (8.2%) | 27/347 (7.8%) | |||
| Urinary tract infection | 15/200 (7.5%) | 15/147 (10.2%) | 30/347 (8.6%) | |||
| Viral infection | 3/200 (1.5%) | 0/147 (0%) | 3/347 (0.9%) | |||
| Viral pharyngitis | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Vulvovaginal candidiasis | 2/200 (1%) | 5/147 (3.4%) | 7/347 (2%) | |||
| Vulvovaginal mycotic infection | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Wound infection bacterial | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Injury, poisoning and procedural complications | ||||||
| Accident | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Contusion | 3/200 (1.5%) | 0/147 (0%) | 3/347 (0.9%) | |||
| Fall | 1/200 (0.5%) | 3/147 (2%) | 4/347 (1.2%) | |||
| Foot fracture | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Ligament sprain | 2/200 (1%) | 1/147 (0.7%) | 3/347 (0.9%) | |||
| Maternal exposure during pregnancy | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Muscle injury | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Road traffic accident | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 2/200 (1%) | 5/147 (3.4%) | 7/347 (2%) | |||
| Aspartate aminotransferase increased | 0/200 (0%) | 5/147 (3.4%) | 5/347 (1.4%) | |||
| B-lymphocyte count decreased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Blood calcium decreased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Blood chloride increased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Blood cholesterol increased | 1/200 (0.5%) | 2/147 (1.4%) | 3/347 (0.9%) | |||
| Blood iron decreased | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Blood pressure increased | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Blood triglycerides increased | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| CD4 lymphocytes decreased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| CD8 lymphocytes decreased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Electrocardiogram T wave abnormal | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Gamma-glutamyltransferase increased | 0/200 (0%) | 3/147 (2%) | 3/347 (0.9%) | |||
| Hepatic enzyme increased | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Liver function test abnormal | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Low density lipoprotein increased | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Lymphocyte count decreased | 1/200 (0.5%) | 2/147 (1.4%) | 3/347 (0.9%) | |||
| Micturition urgency | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| T-lymphocyte count decreased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Transaminases abnormal | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Weight decreased | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Weight increased | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Dyslipidaemia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Hypercholesterolaemia | 3/200 (1.5%) | 4/147 (2.7%) | 7/347 (2%) | |||
| Hypertriglyceridaemia | 1/200 (0.5%) | 2/147 (1.4%) | 3/347 (0.9%) | |||
| Hypocalcaemia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Hypokalaemia | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Hypophosphataemia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Lactose intolerance | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Polydipsia | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Vitamin D deficiency | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/200 (0.5%) | 3/147 (2%) | 4/347 (1.2%) | |||
| Back pain | 12/200 (6%) | 4/147 (2.7%) | 16/347 (4.6%) | |||
| Bursitis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Haemophilic arthropathy | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Muscle contracture | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Muscle spasms | 0/200 (0%) | 3/147 (2%) | 3/347 (0.9%) | |||
| Muscular weakness | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Musculoskeletal pain | 1/200 (0.5%) | 3/147 (2%) | 4/347 (1.2%) | |||
| Musculoskeletal stiffness | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Myokymia | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Neck pain | 5/200 (2.5%) | 6/147 (4.1%) | 11/347 (3.2%) | |||
| Pain in extremity | 2/200 (1%) | 2/147 (1.4%) | 4/347 (1.2%) | |||
| Sjogren's syndrome | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Spondylolisthesis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Synovial cyst | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Tendonitis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Anogenital warts | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Basal cell carcinoma | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Fibroadenoma of breast | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Fibrous histiocytoma | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Melanocytic naevus | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Seborrhoeic keratosis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Skin papilloma | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Superficial spreading melanoma stage unspecified | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Nervous system disorders | ||||||
| Amnesia | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Aphonia | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Balance disorder | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Burning sensation | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Carpal tunnel syndrome | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Cervicobrachial syndrome | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Dizziness | 5/200 (2.5%) | 7/147 (4.8%) | 12/347 (3.5%) | |||
| Dysaesthesia | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Epilepsy | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Head discomfort | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Headache | 17/200 (8.5%) | 17/147 (11.6%) | 34/347 (9.8%) | |||
| Hemiparesis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hyperreflexia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Hypersomnia | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hypoaesthesia | 1/200 (0.5%) | 3/147 (2%) | 4/347 (1.2%) | |||
| Lethargy | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Migraine | 6/200 (3%) | 6/147 (4.1%) | 12/347 (3.5%) | |||
| Migraine with aura | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Migraine without aura | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Multiple sclerosis relapse | 2/200 (1%) | 1/147 (0.7%) | 3/347 (0.9%) | |||
| Neuralgia | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Neurological symptom | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Neuropathy peripheral | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Optic neuritis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Paraesthesia | 3/200 (1.5%) | 4/147 (2.7%) | 7/347 (2%) | |||
| Partial seizures | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Presyncope | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Restless legs syndrome | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Sciatica | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Sensorimotor disorder | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Sleep paralysis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Somnolence | 1/200 (0.5%) | 2/147 (1.4%) | 3/347 (0.9%) | |||
| Syncope | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Tension headache | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Typical aura without headache | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Uhthoff's phenomenon | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| VIIth nerve paralysis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Psychiatric disorders | ||||||
| Adjustment disorder with mixed anxiety and depressed mood | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Anxiety | 11/200 (5.5%) | 6/147 (4.1%) | 17/347 (4.9%) | |||
| Anxiety disorder | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Bruxism | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Confusional state | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Depressed mood | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Depression | 9/200 (4.5%) | 6/147 (4.1%) | 15/347 (4.3%) | |||
| Dysthymic disorder | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Generalised anxiety disorder | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Insomnia | 5/200 (2.5%) | 3/147 (2%) | 8/347 (2.3%) | |||
| Laziness | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Personality disorder | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Renal and urinary disorders | ||||||
| Dysuria | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Lower urinary tract symptoms | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Micturition urgency | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Neurogenic bladder | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Pollakiuria | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Polyuria | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Renal colic | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Renal pain | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Urinary incontinence | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Urinary retention | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Reproductive system and breast disorders | ||||||
| Amenorrhoea | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Benign prostatic hyperplasia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Cervical dysplasia | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Dysmenorrhoea | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Erectile dysfunction | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Menorrhagia | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Menstrual disorder | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Metrorrhagia | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Sexual dysfunction | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/200 (0.5%) | 4/147 (2.7%) | 5/347 (1.4%) | |||
| Dyspnoea | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Epistaxis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Nasal dryness | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Oropharyngeal pain | 3/200 (1.5%) | 1/147 (0.7%) | 4/347 (1.2%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 3/200 (1.5%) | 2/147 (1.4%) | 5/347 (1.4%) | |||
| Actinic keratosis | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Alopecia | 4/200 (2%) | 3/147 (2%) | 7/347 (2%) | |||
| Dermatitis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Dermatitis allergic | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Dermatitis atopic | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Eczema | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Eczema nummular | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Erythema | 0/200 (0%) | 2/147 (1.4%) | 2/347 (0.6%) | |||
| Hand dermatitis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hidradenitis | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hyperhidrosis | 2/200 (1%) | 0/147 (0%) | 2/347 (0.6%) | |||
| Night sweats | 1/200 (0.5%) | 1/147 (0.7%) | 2/347 (0.6%) | |||
| Pain of skin | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Rash | 4/200 (2%) | 0/147 (0%) | 4/347 (1.2%) | |||
| Rash macular | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Rash pruritic | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Seborrhoeic dermatitis | 2/200 (1%) | 2/147 (1.4%) | 4/347 (1.2%) | |||
| Skin depigmentation | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Skin discolouration | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Skin fissures | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Skin hypertrophy | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Skin lesion | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Solar lentigo | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Surgical and medical procedures | ||||||
| Intraocular lens implant | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Skin lesion excision | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Tooth extraction | 1/200 (0.5%) | 0/147 (0%) | 1/347 (0.3%) | |||
| Vascular disorders | ||||||
| Flushing | 0/200 (0%) | 1/147 (0.7%) | 1/347 (0.3%) | |||
| Hypertension | 1/200 (0.5%) | 3/147 (2%) | 4/347 (1.2%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01498887
Other Study ID Numbers:
- CFTY720DES03
- 2011-003484-30
First Posted:
Dec 26, 2011
Last Update Posted:
Jan 25, 2019
Last Verified:
Aug 1, 2018