Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02763046
Recruitment Status : Completed
First Posted : May 5, 2016
Results First Posted : October 9, 2020
Last Update Posted : October 9, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Ankylosing Spondylitis
Interventions Drug: Secukinumab (AIN457) 150 mg s.c.
Drug: Placebo - Secukinumab (AIN457) 150 mg s.c.
Enrollment 211
Recruitment Details Participants took part in 40 investigative sites in Germany.
Pre-assignment Details Participants were randomized 1:1:1 to one of the following treatment groups: secukinumab 150 mg s.c. with delayed NSAID tapering, secukinumab 150 mg s.c. with early NSAID tapering and placebo.
Arm/Group Title Secukinumab - Delayed NSAID Tapering Secukinumab - Early NSAID Tapering Placebo
Hide Arm/Group Description

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (early tapering).

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

NSAID tapering allowed from Week 4.

Period Title: Overall Study
Started 71 70 70
Completed 62 65 62
Not Completed 9 5 8
Reason Not Completed
Adverse Event             5             4             0
Lack of Efficacy             1             1             3
Physician Decision             1             0             1
Subject/guardian decision             2             0             4
Arm/Group Title Secukinumab - Delayed NSAID Tapering Secukinumab - Early NSAID Tapering Placebo Total
Hide Arm/Group Description

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (early tapering).

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

NSAID tapering allowed from Week 4.

Total of all reporting groups
Overall Number of Baseline Participants 71 70 70 211
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 71 participants 70 participants 70 participants 211 participants
46.2  (13.36) 44.1  (11.02) 45.4  (12.55) 45.2  (12.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 70 participants 70 participants 211 participants
Female
30
  42.3%
28
  40.0%
31
  44.3%
89
  42.2%
Male
41
  57.7%
42
  60.0%
39
  55.7%
122
  57.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 70 participants 70 participants 211 participants
Caucasian
69
  97.2%
67
  95.7%
68
  97.1%
204
  96.7%
Black
1
   1.4%
0
   0.0%
0
   0.0%
1
   0.5%
Asian
0
   0.0%
2
   2.9%
1
   1.4%
3
   1.4%
Other
1
   1.4%
1
   1.4%
1
   1.4%
3
   1.4%
1.Primary Outcome
Title Proportion of Patients Who Achieved ASAS20 Response in the Pooled Secukinumab Group Compared With the Placebo Group at Week 12
Hide Description

ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and inflammation represented by mean duration and severity of morning stiffness.

Non-responder imputation was applied for missing data.

Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) comprising all subjects from the randomized set to whom study treatment was assigned.
Arm/Group Title Secukinumab - Pooled Placebo
Hide Arm/Group Description:
The 2 secukinumab arms (delayed NSAID tapering and early NSAID tapering) pooled.

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

NSAID tapering allowed from Week 4.

Overall Number of Participants Analyzed 141 70
Measure Type: Count of Participants
Unit of Measure: Participants
72
  51.1%
31
  44.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Secukinumab - Pooled, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3512
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
0.74 to 2.36
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Patients Who Achieved ASAS20 Response in Each Secukinumab Group (Delayed NSAID Tapering and Early NSAID Tapering) Compared With the Placebo Group
Hide Description

ASAS (Assessment of SpondyloArthritis International Society criteria) 20 response is defined as an improvement from baseline of ≥20% and ≥1 unit on a scale of 0-10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit on a scale of 0-10 in the remaining domain. The four main ASAS domains are: Patient's global assessment of disease activity, back pain, function represented by ability to perform specific tasks (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and inflammation represented by mean duration and severity of morning stiffness.

Non-responder imputation was applied for missing data.

Time Frame Baseline, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprising all subjects from the randomized set to whom study treatment was assigned.
Arm/Group Title Secukinumab - Delayed NSAID Tapering Secukinumab - Early NSAID Tapering Placebo
Hide Arm/Group Description:

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (early tapering).

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

NSAID tapering allowed from Week 4.

Overall Number of Participants Analyzed 71 70 70
Measure Type: Count of Participants
Unit of Measure: Participants
Week 12
37
  52.1%
35
  50.0%
31
  44.3%
Week 16
40
  56.3%
35
  50.0%
29
  41.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Secukinumab - Delayed NSAID Tapering, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4010
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
0.68 to 2.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secukinumab - Early NSAID Tapering, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4382
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.67 to 2.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Secukinumab - Delayed NSAID Tapering, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0934
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.78
Confidence Interval (2-Sided) 95%
0.91 to 3.50
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Secukinumab - Early NSAID Tapering, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2619
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
0.75 to 2.90
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline in ASAS-NSAID Score at Week 12
Hide Description

ASAS-NSAID score is used to present the NSAID (nonsteroidal anti-inflammatory drug) intake by considering the type of NSAID, the total dose and the number of days taking NSAID during a period of interest (PI). For the NSAID equivalence scoring system, "no NSAID intake" was set to a score value of 0, and the reference dose of 150 mg/day diclofenac was set to a score value of 100. The Daily diclofenac-equivalent dose score was derived by converting each daily dose of NSAID to a percentage dose equivalent of 150 mg diclofenac. ASAS-NSAID score = (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).

A negative change from baseline indicates less NSAID consumption.

Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprising all subjects from the randomized set to whom study treatment was assigned.
Arm/Group Title Secukinumab - Delayed NSAID Tapering Secukinumab - Early NSAID Tapering Placebo Secukinumab - Pooled
Hide Arm/Group Description:

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (early tapering).

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

NSAID tapering allowed from Week 4.

The 2 secukinumab arms (delayed NSAID tapering and early NSAID tapering) pooled.
Overall Number of Participants Analyzed 71 70 70 141
Mean (Standard Deviation)
Unit of Measure: Score on scale
-44.9  (47.32) -40.3  (71.48) -31.5  (36.54) -42.6  (60.53)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Secukinumab - Pooled
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0997
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS (least square) Mean
Estimated Value -10.29
Confidence Interval (2-Sided) 95%
-22.55 to 1.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secukinumab - Delayed NSAID Tapering, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0888
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -12.30
Confidence Interval (2-Sided) 95%
-26.47 to 1.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Secukinumab - Early NSAID Tapering, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2484
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -8.29
Confidence Interval (2-Sided) 95%
-22.36 to 5.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.18
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in ASAS-NSAID Score in Each Secukinumab Group After 12 Weeks of Exposure (at Week 12 in the Secukinumab-delayed NSAID Tapering Group and at Week 16 in the Secukinumab-early NSAID Tapering Group)
Hide Description

ASAS-NSAID score is used to present the NSAID (nonsteroidal anti-inflammatory drug) intake by considering the type of NSAID, the total dose and the number of days taking NSAID during a period of interest (PI). For the NSAID equivalence scoring system, "no NSAID intake" was set to a score value of 0, and the reference dose of 150 mg/day diclofenac was set to a score value of 100. The Daily diclofenac-equivalent dose score was derived by converting each daily dose of NSAID to a percentage dose equivalent of 150 mg diclofenac. ASAS-NSAID score = (equivalent NSAID score) x (days of intake during PI) x (days per week)/(PI in days).

A negative change from baseline indicates less NSAID consumption. For this endpoint the analysis was performed after 12 weeks of exposure to secukinumab which was achieved at Week 12 in the secukinumab delayed NSAID tapering group but at Week 16 in the secukinumab early NSAID tapering group.

Time Frame Baseline, Week 12 (delayed NSAID tapering), Week 16 (early NSAID tapering)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprising all subjects from the randomized set to whom study treatment was assigned.
Arm/Group Title Secukinumab - Delayed NSAID Tapering Secukinumab - Early NSAID Tapering
Hide Arm/Group Description:

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (early tapering).

Overall Number of Participants Analyzed 71 70
Mean (Standard Deviation)
Unit of Measure: Score on scale
-44.9  (47.32) -42.5  (68.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Secukinumab - Delayed NSAID Tapering, Secukinumab - Early NSAID Tapering
Comments delayed tapering (W12) vs early tapering (W16)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7735
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -2.06
Confidence Interval (2-Sided) 95%
-16.11 to 11.98
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline in the BASDAI Total Score
Hide Description

The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) is a participant-reported assessment consisting of 6 questions that relate to 5 major symptoms relevant to ankylosing spondylitis: 1) Fatigue, 2) Spinal pain, 3) Peripheral arthritis, 4) Enthesitis, 5) Intensity, and 6) Duration of morning stiffness. Participants need to score each item with a score from 0 to 10 (captured as a continuous visual analog scale). Total score is obtained from the average of symptom scores ranging 0 (no problem) to 10 (worst problem), with a higher score indicating more severe symptoms.

A negative change from baseline in the total 0-10 BASDAI score indicates improvement.

Time Frame Baseline, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprising all subjects from the randomized set to whom study treatment was assigned.
Arm/Group Title Secukinumab - Delayed NSAID Tapering Secukinumab - Early NSAID Tapering Placebo Secukinumab - Pooled
Hide Arm/Group Description:

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (early tapering).

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

NSAID tapering allowed from Week 4.

The 2 secukinumab arms (delayed NSAID tapering and early NSAID tapering) pooled.
Overall Number of Participants Analyzed 71 70 70 141
Mean (Standard Deviation)
Unit of Measure: Score on scale
Week 12 -2.1  (2.16) -2.0  (2.10) -1.8  (2.00) -2.1  (2.12)
Week 16 -2.3  (1.90) -2.0  (1.96) -1.7  (1.96) -2.2  (1.93)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Secukinumab - Pooled
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1926
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.99 to 0.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secukinumab - Delayed NSAID Tapering, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1914
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-1.14 to 0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Secukinumab - Early NSAID Tapering, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3397
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-1.01 to 0.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Secukinumab - Delayed NSAID Tapering, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0384
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-1.33 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Secukinumab - Early NSAID Tapering, Placebo
Comments Week 16
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2116
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-1.05 to 0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline in Health-related Quality of Life as Measured by the Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score
Hide Description The Short Form-36 Health Survey (SF-36) measures the impact of disease on overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36 (SF-36 PCS) that is evaluated in this study. Scores on each item 1-4 were summed and averaged (range = 0-100 with higher scores indicating better levels of function and/or better health). A positive change from Baseline indicates improvement.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS comprising all subjects from the randomized set to whom study treatment was assigned.
Arm/Group Title Secukinumab - Delayed NSAID Tapering Secukinumab - Early NSAID Tapering Placebo Secukinumab - Pooled
Hide Arm/Group Description:

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (delayed tapering).

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind.

NSAID tapering allowed from Week 4 (early tapering).

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20).

NSAID tapering allowed from Week 4.

The 2 secukinumab arms (delayed NSAID tapering and early NSAID tapering) pooled.
Overall Number of Participants Analyzed 71 70 70 141
Mean (Standard Deviation)
Unit of Measure: Score on scale
4.8  (7.03) 6.1  (6.92) 4.8  (7.43) 5.5  (6.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Secukinumab - Pooled
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5384
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
-1.38 to 2.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Secukinumab - Delayed NSAID Tapering, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9251
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-2.43 to 2.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Secukinumab - Early NSAID Tapering, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2432
Comments [Not Specified]
Method Mixed Model for Repeated Measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
-0.93 to 3.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
Time Frame Adverse events were collected from first dose of study treatment until end of study treatment plus 4 weeks post-treatment (median duration of 24 weeks).
Adverse Event Reporting Description Any signs or symptoms that occurs from first study drug treatment until 30 days after the last study drug treatment. Adverse events were analyzed by treatment period, i.e., Treatment Period 1 from first study drug administration at baseline through Week 16 (concretely: until the day before the injection of study drug scheduled at visit Week 16) and Treatment Period 2 (from the day of injection at visit Week 16 onwards until study end).
 
Arm/Group Title Secukinumab - Delayed NSAID Tapering - Treatment Period 1 Secukinumab - Early NSAID Tapering - Treatment Period 1 Placebo - Treatment Period 1 Secukinumab - Delayed NSAID Tapering - Treatment Period 2 Secukinumab - Early NSAID Tapering - Treatment Period 2 Placebo - Treatment Period 2
Hide Arm/Group Description

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).

Treatment Period 1: from first study drug administration at baseline through Week 16 (concretely: until the day before the injection of study drug scheduled at visit Week 16). This corresponds to the placebo-controlled period of the study.

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).

Treatment Period 1: from first study drug administration at baseline through Week 16 (concretely: until the day before the injection of study drug scheduled at visit Week 16). This corresponds to the placebo-controlled period of the study.

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

Treatment Period 1: from first study drug administration at baseline through Week 16 (concretely: until the day before the injection of study drug scheduled at visit Week 16). This corresponds to the placebo-controlled period of the study.

Induction with secukinumab 150 mg s.c. once per week (Week 0, 1, 2, 3 and 4) followed by maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 8, 12, 16 and 20), with intermittent placebo injections at Week 5, 6, 7, 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (delayed tapering).

Treatment Period 2: from the day of injection at visit Week 16 onwards until study end.

Placebo at weeks 0, 1, 2, 3 to maintain the blind; followed by induction with secukinumab 150 mg s.c. once per week (Week 4, 5, 6, 7, 8) and maintenance with secukinumab 150 mg s.c. every 4 weeks (Week 12, 16 and 20), with intermittent placebo injections at Week 17, 18 and 19 to maintain the blind. NSAID tapering allowed from Week 4 (early tapering).

Treatment Period 2: from the day of injection at visit Week 16 onwards until study end.

Placebo s.c. at Week 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments of the secondary endpoint had been performed, these patients received weekly doses of secukinumab 150 mg s.c. (Week 16, 17, 18, 19 and 20). NSAID tapering allowed from Week 4.

Treatment Period 2: from the day of injection at visit Week 16 onwards until study end.

All-Cause Mortality
Secukinumab - Delayed NSAID Tapering - Treatment Period 1 Secukinumab - Early NSAID Tapering - Treatment Period 1 Placebo - Treatment Period 1 Secukinumab - Delayed NSAID Tapering - Treatment Period 2 Secukinumab - Early NSAID Tapering - Treatment Period 2 Placebo - Treatment Period 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/71 (0.00%)   0/70 (0.00%)   0/70 (0.00%)   0/71 (0.00%)   0/70 (0.00%)   0/70 (0.00%) 
Hide Serious Adverse Events
Secukinumab - Delayed NSAID Tapering - Treatment Period 1 Secukinumab - Early NSAID Tapering - Treatment Period 1 Placebo - Treatment Period 1 Secukinumab - Delayed NSAID Tapering - Treatment Period 2 Secukinumab - Early NSAID Tapering - Treatment Period 2 Placebo - Treatment Period 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/71 (5.63%)   3/70 (4.29%)   1/70 (1.43%)   1/71 (1.41%)   0/70 (0.00%)   1/70 (1.43%) 
Eye disorders             
Iridocyclitis  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Gastrointestinal disorders             
Abdominal hernia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Abdominal pain  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Colitis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Crohn's disease  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gastritis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Inguinal hernia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Oesophageal ulcer  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Infections and infestations             
Erysipelas  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Renal and urinary disorders             
Nephrolithiasis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Reproductive system and breast disorders             
Vaginal cyst  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Skin and subcutaneous tissue disorders             
Psoriasis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Secukinumab - Delayed NSAID Tapering - Treatment Period 1 Secukinumab - Early NSAID Tapering - Treatment Period 1 Placebo - Treatment Period 1 Secukinumab - Delayed NSAID Tapering - Treatment Period 2 Secukinumab - Early NSAID Tapering - Treatment Period 2 Placebo - Treatment Period 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   53/71 (74.65%)   56/70 (80.00%)   55/70 (78.57%)   25/71 (35.21%)   23/70 (32.86%)   22/70 (31.43%) 
Blood and lymphatic system disorders             
Anaemia  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Iron deficiency anaemia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Leukopenia  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Lymph node pain  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Lymphopenia  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Monoclonal B-cell lymphocytosis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Monocytosis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Neutrophilia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Cardiac disorders             
Bradycardia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Coronary artery disease  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Palpitations  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Tachycardia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Ear and labyrinth disorders             
Ear pain  1  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Tinnitus  1  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Vertigo  1  1/71 (1.41%)  0/70 (0.00%)  3/70 (4.29%)  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%) 
Endocrine disorders             
Hyperprolactinaemia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hypothyroidism  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Eye disorders             
Diplopia  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Dry eye  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Eye irritation  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Eye pain  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Iritis  1  0/71 (0.00%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Macular degeneration  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Presbyopia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Uveitis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Visual impairment  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gastrointestinal disorders             
Abdominal pain  1  3/71 (4.23%)  3/70 (4.29%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Abdominal pain lower  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Abdominal pain upper  1  3/71 (4.23%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Aphthous ulcer  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Colitis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Constipation  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Diarrhoea  1  3/71 (4.23%)  3/70 (4.29%)  3/70 (4.29%)  1/71 (1.41%)  1/70 (1.43%)  3/70 (4.29%) 
Diarrhoea haemorrhagic  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Dry mouth  1  0/71 (0.00%)  2/70 (2.86%)  1/70 (1.43%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Dyspepsia  1  0/71 (0.00%)  3/70 (4.29%)  1/70 (1.43%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Dysphagia  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Enteritis  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Frequent bowel movements  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gastritis  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gastrooesophageal reflux disease  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gingival discomfort  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Haematochezia  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hiatus hernia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Inguinal hernia  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Nausea  1  2/71 (2.82%)  2/70 (2.86%)  5/70 (7.14%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Stomatitis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Toothache  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
General disorders             
Discomfort  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Fatigue  1  0/71 (0.00%)  1/70 (1.43%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Feeling hot  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Impaired healing  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Influenza like illness  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Injection site pruritus  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Injection site urticaria  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Non-cardiac chest pain  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Oedema peripheral  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Peripheral swelling  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Polyp  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Pyrexia  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Thirst  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hepatobiliary disorders             
Cholelithiasis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hepatic steatosis  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Immune system disorders             
Allergy to arthropod bite  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Seasonal allergy  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Infections and infestations             
Bacterial vaginosis  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Bronchitis  1  5/71 (7.04%)  2/70 (2.86%)  3/70 (4.29%)  2/71 (2.82%)  1/70 (1.43%)  1/70 (1.43%) 
Candida infection  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Conjunctivitis  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  2/71 (2.82%)  0/70 (0.00%)  0/70 (0.00%) 
Cystitis  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Epstein-Barr virus infection  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Erysipelas  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Folliculitis  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Fungal infection  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Fungal skin infection  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Furuncle  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gastroenteritis  1  2/71 (2.82%)  4/70 (5.71%)  3/70 (4.29%)  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%) 
Gastroenteritis viral  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Gastrointestinal infection  1  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gastrointestinal viral infection  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Herpes simplex  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Infected bite  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Influenza  1  1/71 (1.41%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Laryngitis  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Lower respiratory tract infection  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Lyme disease  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Nasopharyngitis  1  6/71 (8.45%)  13/70 (18.57%)  14/70 (20.00%)  7/71 (9.86%)  5/70 (7.14%)  3/70 (4.29%) 
Oesophageal candidiasis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Onychomycosis  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Oral candidiasis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Oral herpes  1  2/71 (2.82%)  2/70 (2.86%)  0/70 (0.00%)  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%) 
Otitis externa  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Otitis media  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Pharyngitis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Pneumonia  1  0/71 (0.00%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Pulpitis dental  1  1/71 (1.41%)  2/70 (2.86%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Respiratory tract infection  1  2/71 (2.82%)  4/70 (5.71%)  3/70 (4.29%)  1/71 (1.41%)  1/70 (1.43%)  3/70 (4.29%) 
Respiratory tract infection viral  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Rhinitis  1  4/71 (5.63%)  0/70 (0.00%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Sinusitis  1  0/71 (0.00%)  0/70 (0.00%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Subcutaneous abscess  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Trichomoniasis  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Upper respiratory tract infection  1  1/71 (1.41%)  3/70 (4.29%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  2/70 (2.86%) 
Urinary tract infection  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Uterine infection  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Injury, poisoning and procedural complications             
Animal bite  1  0/71 (0.00%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Bone contusion  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Contusion  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Fall  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Hand fracture  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Joint dislocation  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Ligament rupture  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Ligament sprain  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Limb injury  1  0/71 (0.00%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Muscle injury  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Muscle strain  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Overdose  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Post-traumatic neck syndrome  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%) 
Reactive gastropathy  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Road traffic accident  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%) 
Spinal column injury  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Wound  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Investigations             
Alanine aminotransferase increased  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Aspartate aminotransferase increased  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Blood glucose increased  1  2/71 (2.82%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Blood pressure decreased  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Blood pressure increased  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Gamma-glutamyltransferase increased  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hepatic enzyme increased  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Laboratory test abnormal  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Liver function test increased  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Lymphocyte count decreased  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Red blood cell sedimentation rate increased  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Transaminases increased  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Weight decreased  1  2/71 (2.82%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
White blood cell count decreased  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
White blood cell count increased  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Diabetes mellitus  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hypercholesterolaemia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Pseudohyperkalaemia  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Pseudohypoglycaemia  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Musculoskeletal and connective tissue disorders             
Ankylosing spondylitis  1  3/71 (4.23%)  1/70 (1.43%)  6/70 (8.57%)  2/71 (2.82%)  0/70 (0.00%)  1/70 (1.43%) 
Arthralgia  1  2/71 (2.82%)  2/70 (2.86%)  2/70 (2.86%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Arthritis  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Back pain  1  4/71 (5.63%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Bursitis  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Joint swelling  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Muscle spasms  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Muscle tightness  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Musculoskeletal chest pain  1  0/71 (0.00%)  0/70 (0.00%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Musculoskeletal pain  1  0/71 (0.00%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Myalgia  1  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Osteoarthritis  1  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Pain in extremity  1  1/71 (1.41%)  2/70 (2.86%)  1/70 (1.43%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Rheumatic fever  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Sacroiliitis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Spinal osteoarthritis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Spinal pain  1  0/71 (0.00%)  1/70 (1.43%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Spondylitis  1  0/71 (0.00%)  1/70 (1.43%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Spondyloarthropathy  1  1/71 (1.41%)  0/70 (0.00%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Spondylolisthesis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Synovial cyst  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Tendon disorder  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Tendon pain  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Tendonitis  1  0/71 (0.00%)  1/70 (1.43%)  1/70 (1.43%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Tenosynovitis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Nervous system disorders             
Ageusia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Autonomic nervous system imbalance  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Cervicobrachial syndrome  1  1/71 (1.41%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Disturbance in attention  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Dizziness  1  0/71 (0.00%)  2/70 (2.86%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Dysaesthesia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Dysgeusia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Headache  1  12/71 (16.90%)  10/70 (14.29%)  6/70 (8.57%)  4/71 (5.63%)  3/70 (4.29%)  1/70 (1.43%) 
Intercostal neuralgia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Migraine  1  1/71 (1.41%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Nerve compression  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Paraesthesia  1  2/71 (2.82%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Paresis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Presyncope  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Sciatica  1  1/71 (1.41%)  1/70 (1.43%)  1/70 (1.43%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Tension headache  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Tremor  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Psychiatric disorders             
Apathy  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Depression  1  1/71 (1.41%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Insomnia  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Nervousness  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Restlessness  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Sleep disorder  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Renal and urinary disorders             
Dysuria  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Haematuria  1  1/71 (1.41%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Proteinuria  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Renal failure  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Urinary incontinence  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Reproductive system and breast disorders             
Dysmenorrhoea  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Menorrhagia  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Uterine pain  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Vaginal haemorrhage  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Vulvovaginal pain  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Asthma  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Chronic obstructive pulmonary disease  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Cough  1  2/71 (2.82%)  0/70 (0.00%)  2/70 (2.86%)  0/71 (0.00%)  3/70 (4.29%)  0/70 (0.00%) 
Dyspnoea exertional  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Nasal congestion  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Oropharyngeal pain  1  0/71 (0.00%)  2/70 (2.86%)  1/70 (1.43%)  0/71 (0.00%)  3/70 (4.29%)  0/70 (0.00%) 
Rhinorrhoea  1  0/71 (0.00%)  2/70 (2.86%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Skin and subcutaneous tissue disorders             
Angioedema  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Dermatitis  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Dyshidrotic eczema  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Eczema  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Eczema asteatotic  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Erythema  1  1/71 (1.41%)  0/70 (0.00%)  2/70 (2.86%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Guttate psoriasis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hyperhidrosis  1  0/71 (0.00%)  2/70 (2.86%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Night sweats  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Palmoplantar pustulosis  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Photosensitivity reaction  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Pruritus  1  1/71 (1.41%)  1/70 (1.43%)  3/70 (4.29%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Psoriasis  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Rash  1  2/71 (2.82%)  1/70 (1.43%)  3/70 (4.29%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Rash maculo-papular  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Seborrhoea  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Skin exfoliation  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Skin fissures  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Skin irritation  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Solar dermatitis  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%) 
Xeroderma  1  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%)  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%) 
Vascular disorders             
Circulatory collapse  1  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Haematoma  1  1/71 (1.41%)  0/70 (0.00%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
Hypertension  1  4/71 (5.63%)  3/70 (4.29%)  4/70 (5.71%)  0/71 (0.00%)  0/70 (0.00%)  1/70 (1.43%) 
Hypotension  1  0/71 (0.00%)  1/70 (1.43%)  0/70 (0.00%)  0/71 (0.00%)  0/70 (0.00%)  0/70 (0.00%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02763046    
Other Study ID Numbers: CAIN457FDE03
2015-004575-74 ( EudraCT Number )
First Submitted: May 3, 2016
First Posted: May 5, 2016
Results First Submitted: September 16, 2020
Results First Posted: October 9, 2020
Last Update Posted: October 9, 2020