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Safety and Efficacy of AIN457 in Noninfectious Uveitis

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ClinicalTrials.gov Identifier: NCT00685399
Recruitment Status : Completed
First Posted : May 28, 2008
Results First Posted : July 17, 2017
Last Update Posted : July 17, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Non-infectious Uveitis
Interventions Drug: AIN457
Drug: AIN 457
Enrollment 76
Recruitment Details This is a multi-center study which comprised of 6 cohorts. This study was a proof of concept study.
Pre-assignment Details  
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Arm 1 Cohort 6 Arm 2 Cohort 6 Arm 3
Hide Arm/Group Description Participants were administered with AIN457 (Sp2/0-derived) 10 milligrams per kilogram (mg/kg) intravenous (i.v.) dose on Day 1 and Day 22. Participants were administered with AIN457 (Sp2/0 or Chinese hamster ovary cell (CHO) derived) 10 mg/kg, (CHO-derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed a second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort. Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22. Participants who experienced a remission of their uveitis within 8 weeks after receiving their final dose of AIN457 while enrolled in Cohorts 1, 2, 3, 5 or 6 were administered with AIN457 10 mg/kg, i.v. infusion (with or without a short course of corticosteroids) once a flare had occurred, or periodically at a frequency of not more than once per month at the discretion of the investigator. Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well tolerated by all. Participants were administered with AIN457 300 mg subcutaneously (s.c.) and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43). Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43). Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups.
Period Title: Treatment Period 1
Started 16 0 0 0 0 0 0 0
Completed 10 0 0 0 0 0 0 0
Not Completed 6 0 0 0 0 0 0 0
Reason Not Completed
Withdrawal by Subject             2             0             0             0             0             0             0             0
Protocol Violation             1             0             0             0             0             0             0             0
Administrative             2             0             0             0             0             0             0             0
Lack of Efficacy             1             0             0             0             0             0             0             0
Period Title: Treatment Period 2
Started 0 14 5 0 [1] 4 12 13 12
Completed 0 2 2 0 [1] 4 10 13 10
Not Completed 0 12 3 0 0 2 0 2
Reason Not Completed
Administrative Problems             0             2             1             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             0             2
Adverse Event             0             0             0             0             0             1             0             0
Lack of Efficacy             0             10             2             0             0             1             0             0
[1]
in extension period only
Period Title: Extension
Started 0 0 0 28 0 0 0 0
Completed 0 0 0 21 0 0 0 0
Not Completed 0 0 0 7 0 0 0 0
Reason Not Completed
Administrative Issues             0             0             0             1             0             0             0             0
Withdrawal by Subject             0             0             0             1             0             0             0             0
Protocol Violation             0             0             0             1             0             0             0             0
Lack of Efficacy             0             0             0             2             0             0             0             0
Adverse Event             0             0             0             2             0             0             0             0
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 5 Cohort 6 Arm 1 Cohort 6 Arm 2 Cohort 6 Arm 3 Total
Hide Arm/Group Description Participants were administered with AIN457 (Sp2/0-derived) 10 mg/kg i.v. dose on Day 1 and Day 22. Participants were administered with AIN457 (Sp2/0 or CHO derived) 10 mg/kg, (CHO-derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort. Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22. Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well tolerated by all. Participants were administered with AIN457 300 mg s.c. and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43). Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43). Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups. Total of all reporting groups
Overall Number of Baseline Participants 16 14 5 4 12 13 12 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 14 participants 5 participants 4 participants 12 participants 13 participants 12 participants 76 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
0
   0.0%
1
   1.3%
Between 18 and 65 years
15
  93.8%
13
  92.9%
5
 100.0%
4
 100.0%
12
 100.0%
11
  84.6%
12
 100.0%
72
  94.7%
>=65 years
1
   6.3%
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
1
   7.7%
0
   0.0%
3
   3.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 14 participants 5 participants 4 participants 12 participants 13 participants 12 participants 76 participants
Female
12
  75.0%
10
  71.4%
3
  60.0%
3
  75.0%
8
  66.7%
9
  69.2%
9
  75.0%
54
  71.1%
Male
4
  25.0%
4
  28.6%
2
  40.0%
1
  25.0%
4
  33.3%
4
  30.8%
3
  25.0%
22
  28.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 14 participants 5 participants 4 participants 12 participants 13 participants 12 participants 76 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   6.3%
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  18.8%
3
  21.4%
0
   0.0%
0
   0.0%
2
  16.7%
2
  15.4%
3
  25.0%
13
  17.1%
White
7
  43.8%
10
  71.4%
4
  80.0%
1
  25.0%
9
  75.0%
9
  69.2%
8
  66.7%
48
  63.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
  31.3%
1
   7.1%
1
  20.0%
2
  50.0%
1
   8.3%
2
  15.4%
1
   8.3%
13
  17.1%
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died
Hide Description AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time Frame Day 1 to Day 603
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAS) consisted of all participants who received at least one dose of study drug and had at least one post-baseline safety assessment. All safety evaluations were carried out on the safety analysis set.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Arm 1 Cohort 6 Arm 2 Cohort 6 Arm 3
Hide Arm/Group Description:
Participants were administered with AIN457 (Sp2/0-derived) 10 mg/kg i.v. dose on Day 1 and Day 22.
Participants were administered with AIN457 (Sp2/0 or CHO derived) 10 mg/kg, (CHO-derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort.
Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.
Participants were administered with AIN457 10 mg/kg, i.v. (with or without a short course of corticosteroids) once a flare had occurred, or periodically at a frequency of not more than once per month at the discretion of the investigator.
Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well tolerated by all.
Participants were administered with AIN457 300 mg s.c. and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43).
Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43).
Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups.
Overall Number of Participants Analyzed 16 17 5 28 4 12 13 12
Measure Type: Number
Unit of Measure: participants
SAEs 0 0 1 1 0 1 0 0
Deaths 0 0 0 0 0 0 0 0
AEs 15 12 5 23 3 10 10 12
2.Secondary Outcome
Title Number of Responders in Cohort 1, 2, 3 and 6 at Day 57
Hide Description A "responder" was defined as a participant who fulfilled at least one of the 3 criteria compared to baseline: 1. Increase in visual acuity by at least 15 letters using Early Treatment Diabetic Retinopathy Study method, no increase in daily prednisone dose compared to week 1 and without worsening of uveitis. 2. Decrease in vitreous haze by 2 steps or more or for participants with anterior uveitis, resolution of the anterior chamber inflammation (i.e., no cells or only a rare cell in the anterior chamber (score 0 or trace (0.5+)), use measurement before dilation), no increase in daily prednisone dose compared to week 1 and without any worsening of uveitis.3 For those participant on a. >20 mg/day of prednisone during week 1: Reduction in daily prednisone dose to 10 mg/day or less. b. ≤20 mg/day of prednisone during week 1: Reduction in daily prednisone dose to 0 mg/day. c. topical corticosteroids during week 1: Reduction in daily topical corticosteroid dose to 0 during the last 2 weeks.
Time Frame Day 1 (Baseline), Day 57
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol Analysis Set (PPAS) consisted of all participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have at least one post-baseline assessment for one of the outcomes that define participants who respond.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 6 Arm 1 Cohort 6 Arm 2 Cohort 6 Arm 3
Hide Arm/Group Description:
Participants were administered with AIN457 (Sp2/0-derived) 10 mg/kg i.v. dose on Day 1 and Day 22.
Participants were administered with AIN457 (Sp2/0 or CHO derived) 10 mg/kg, (CHO-derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort.
Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.
Participants were administered with AIN457 300 mg s.c. and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43).
Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43).
Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups.
Overall Number of Participants Analyzed 15 14 5 12 13 11
Measure Type: Number
Unit of Measure: Participants
Intermediate uveitis 0 1 0 1 1 3
Pars planitis 0 0 0 0 0 0
Posterior uveitis 3 0 0 1 2 0
Panuveitis 5 4 0 2 5 5
Anterior uveitis 3 1 0 0 0 0
Birdshot 0 0 2 0 0 0
Sympathetic ophthalmia 0 0 1 0 0 0
Multi-focal choroiditis 0 0 0 0 0 0
3.Secondary Outcome
Title Number of Complete Responders in Cohort 2, 3 and 6 at Day 57
Hide Description A "complete responder" was defined as a participant who was able to stop all topical and systemic corticosteroids in both eyes and maintain remission of uveitis (=remains a responder as defined above) lasting at least 1 week (since stopping corticosteroids, if corticosteroids were given).
Time Frame Day 1 (Baseline), Day 57
Hide Outcome Measure Data
Hide Analysis Population Description
PPAS consisted of all participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have at least one post-baseline assessment for one of the outcomes that define participants who respond.
Arm/Group Title Cohort 2 Cohort 3 Cohort 6 Arm 1 Cohort 6 Arm 2 Cohort 6 Arm 3
Hide Arm/Group Description:
Participants were administered with AIN457 (Sp2/0 or CHO derived) 10 mg/kg, (CHO-derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. 3 participants from cohort 1 rolled on into this cohort.
Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22.
Participants were administered with AIN457 300 mg s.c. and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43).
Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43).
Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups.
Overall Number of Participants Analyzed 14 5 12 13 11
Measure Type: Number
Unit of Measure: Participants
Intermediate uveitis 0 0 0 1 1
Panuveitis 1 0 1 2 2
Pars planitis 0 0 0 0 0
Anterior uveitis 1 0 0 0 0
Birdshot 0 2 0 0 0
Sympathetic ophthalmia 0 1 0 0 0
Multi-focal choroiditis 0 0 0 0 0
Posterior uveitis 0 0 1 2 0
4.Secondary Outcome
Title Number of Participants With Reduction in Oral Prednisone or Topical Corticosteroid and Other Immunosuppressant Drugs
Hide Description Participants intake of oral prednisone or topical corticosteroid and other immunosuppressant drugs was reduced if participant was on up to 1.5 mg/kg/day dose of prednisone during the week prior to Day 1 or whom the resumption of prednisone was not considered the appropriate systemic therapy by investigator or who have never been on systemic immunosuppressive therapy and whose uveitis was so severe that, in the clinician's judgment, prednisone at a dose of 1.0-1.5 mg/kg/day alone will be insufficient to control the uveitis or participant with HLA-B27-associated anterior uveitis who would ordinarily be started on systemic prednisone. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Time Frame Baseline (Day 1) up to Month 8
Hide Outcome Measure Data
Hide Analysis Population Description
PPAS consisted of all participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have at least one post-baseline assessment for one of the outcomes that define participants who respond.
Arm/Group Title Complete Study
Hide Arm/Group Description:
All participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have non-missing values at both Day 1 and Day 57 for at least one of the outcomes that define participants who respond.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Number of Participants Who Were Able to Induce a Remission in Uveitis
Hide Description Participants with uveitis who were able to stop all topical and systemic topical corticosteroids in both eyes by Day 57 visit after the first course of one or two doses of AIN457 were to be categorized as nonresponders and were to be discontinued from the study at the Day 85 visit. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Time Frame Day 1 to Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
PPAS consisted of all participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have at least one post-baseline assessment for one of the outcomes that define participants who respond.
Arm/Group Title Complete Study
Hide Arm/Group Description:
All participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have non-missing values at both Day 1 and Day 57 for at least one of the outcomes that define participants who respond.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Number of Participants With Remission in Uveitis
Hide Description Participants with uveitis who were able to stop all topical and systemic topical corticosteroids in both eyes after the first course of one or two doses by Day 57 visit . The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Time Frame Baseline (Day 1) up to Month 8
Hide Outcome Measure Data
Hide Analysis Population Description
PPAS consisted of all participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have at least one post-baseline assessment for one of the outcomes that define participants who respond.
Arm/Group Title Complete Study
Hide Arm/Group Description:
All participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have non-missing values at both Day 1 and Day 57 for at least one of the outcomes that define participants who respond.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Number of Participants Who Were Able to Re-induce a Remission if a Flare-up Occurs
Hide Description A flare was defined as an increase of inflammation in either eye so that the anterior chamber cell score or the vitreous haze score become 1+ or greater. Vitreous haze was evaluated with an indirect ophthalmoscope and a hand-held 20-diopter lens. Haze is defined as a reduction in the clarity of fundus details seen through the vitreous, the degree of haze was quantified using standard National Eye Institute (NEI) photographs. The standard photographs provide a grading scale with photographs of fundi with vitreous haze grades "0" (zero), "trace" (which counts as 0.5+), 1+, 2+, 3+, and 4+. If the amount of vitreous haze appears to fall between two integer grades, the value would be recorded as halfway between the grades. The analysis was not conducted due to small sample size, insufficient number of participants and low initial doses; limited conclusions were drawn about dose response relationship leading to non summarization of results.
Time Frame Day 1 to Day 57
Hide Outcome Measure Data
Hide Analysis Population Description
PPAS consisted of all participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have at least one post-baseline assessment for one of the outcomes that define participants who respond.
Arm/Group Title Complete Study
Hide Arm/Group Description:
All participants who received study drug, completed the treatment phase of the trial without clinically significant protocol deviations and have non-missing values at both Day 1 and Day 57 for at least one of the outcomes that define participants who respond.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Day 1 to Day 603 (End of study)
Adverse Event Reporting Description AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects.
 
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Cohort 5 Cohort 6 - Arm 1 Cohort 6 - Arm 2 Cohort 6 - Arm 3 Cohort 4 (Extension)
Hide Arm/Group Description Participants were administered with AIN457 (Sp2/0-derived) 10 mg/kg i.v. dose on Day 1 and Day 22. Participants were administered with AIN457 (Sp2/0 or CHO derived) 10 mg/kg, (CHO-derived) 3 mg/kg or (CHO derived) 1 mg/kg i.v. dose on Day 1 and if needed second dose of AIN457 10 mg/kg i.v. dose either on Day 15 or Day 22. Participants were administered with AIN457 10 mg/kg i.v. dose on Day 1 and Day 22. Participants were administered with AIN457 30 mg/kg single i.v. dose. A second dose was given when all 4 participants completed at least 29 days, and the 30 mg/kg dose was well tolerated by all. Participants were administered with AIN457 300 mg s.c.and saline i.v. infusion every two weeks (Days 1, 15, 29, and 43). Participants were administered with AIN457 10 mg/kg i.v. and s.c. saline injections every two weeks (Days 1, 15, 29, and 43). Participants were administered with AIN457 30 mg/kg i.v. and s.c. saline injections every 4 weeks (Days 1 and 29) and saline i.v. infusions and saline s.c. injections on Days 15 and 43 to maintain masking of treatment groups. Participants were administered with AIN457 10 mg/kg, i.v. (with or without a short course of corticosteroids) once a flare had occurred, or periodically at a frequency of not more than once per month at the discretion of the investigator.
All-Cause Mortality
Cohort 1 Cohort 2 Cohort 3 Cohort 5 Cohort 6 - Arm 1 Cohort 6 - Arm 2 Cohort 6 - Arm 3 Cohort 4 (Extension)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/17 (0.00%)   0/5 (0.00%)   0/4 (0.00%)   0/12 (0.00%)   0/13 (0.00%)   0/12 (0.00%)   0/28 (0.00%) 
Hide Serious Adverse Events
Cohort 1 Cohort 2 Cohort 3 Cohort 5 Cohort 6 - Arm 1 Cohort 6 - Arm 2 Cohort 6 - Arm 3 Cohort 4 (Extension)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/17 (0.00%)   1/5 (20.00%)   0/4 (0.00%)   1/12 (8.33%)   0/13 (0.00%)   0/12 (0.00%)   1/28 (3.57%) 
Infections and infestations                 
Pyelonephritis  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Urinary tract infection  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Injury, poisoning and procedural complications                 
Tibia fracture  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Metabolism and nutrition disorders                 
Hypokalaemia  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Uterine cancer  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1 Cohort 2 Cohort 3 Cohort 5 Cohort 6 - Arm 1 Cohort 6 - Arm 2 Cohort 6 - Arm 3 Cohort 4 (Extension)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/16 (93.75%)   12/17 (70.59%)   5/5 (100.00%)   3/4 (75.00%)   9/12 (75.00%)   10/13 (76.92%)   12/12 (100.00%)   20/28 (71.43%) 
Cardiac disorders                 
Palpitations  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Ear and labyrinth disorders                 
Ear pain  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Endocrine disorders                 
Hypothyroidism  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Eye disorders                 
Abnormal sensation in eye  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Anterior chamber flare  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Cataract  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Chalazion  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Colour blindness acquired  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Conjunctival hyperaemia  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Conjunctivitis allergic  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  3/28 (10.71%) 
Corneal disorder  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Dry eye  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  2/13 (15.38%)  0/12 (0.00%)  2/28 (7.14%) 
Eye irritation  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Eye pain  1  3/16 (18.75%)  2/17 (11.76%)  1/5 (20.00%)  0/4 (0.00%)  1/12 (8.33%)  1/13 (7.69%)  1/12 (8.33%)  3/28 (10.71%) 
Eye pruritus  1  1/16 (6.25%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Eye swelling  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Eyelid oedema  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  2/28 (7.14%) 
Foreign body sensation in eyes  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Iridocyclitis  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  2/12 (16.67%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Iris adhesions  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Iris bombe  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Keratoconjunctivitis sicca  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Lacrimation increased  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Macular fibrosis  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  1/28 (3.57%) 
Macular oedema  1  1/16 (6.25%)  2/17 (11.76%)  0/5 (0.00%)  1/4 (25.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Ocular hyperaemia  1  2/16 (12.50%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  3/28 (10.71%) 
Papilloedema  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Photophobia  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  2/28 (7.14%) 
Photopsia  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Pupillary reflex impaired  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Retinal detachment  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Retinal tear  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Scleritis  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Uveitis  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  2/12 (16.67%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Vision blurred  1  3/16 (18.75%)  1/17 (5.88%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  3/12 (25.00%)  1/28 (3.57%) 
Visual acuity reduced  1  2/16 (12.50%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Vitreous detachment  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Vitreous floaters  1  1/16 (6.25%)  1/17 (5.88%)  2/5 (40.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  4/28 (14.29%) 
Vitreous haemorrhage  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Gastrointestinal disorders                 
Abdominal distension  1  1/16 (6.25%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Abdominal pain  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  1/4 (25.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Abdominal pain lower  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Abdominal pain upper  1  3/16 (18.75%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Constipation  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Diarrhoea  1  0/16 (0.00%)  2/17 (11.76%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Inguinal hernia  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Mouth ulceration  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Nausea  1  1/16 (6.25%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Tooth disorder  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Vomiting  1  2/16 (12.50%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
General disorders                 
Fatigue  1  2/16 (12.50%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  2/13 (15.38%)  2/12 (16.67%)  1/28 (3.57%) 
Infusion site extravasation  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Irritability  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  1/28 (3.57%) 
Oedema peripheral  1  0/16 (0.00%)  0/17 (0.00%)  2/5 (40.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Pain  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  1/28 (3.57%) 
Pyrexia  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Hepatobiliary disorders                 
Non-alcoholic steatohepatitis  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Immune system disorders                 
Seasonal allergy  1  2/16 (12.50%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Infections and infestations                 
Cellulitis  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Ear infection  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  1/4 (25.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Gastroenteritis  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Herpes zoster  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Hordeolum  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Lice infestation  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Nasopharyngitis  1  1/16 (6.25%)  1/17 (5.88%)  1/5 (20.00%)  0/4 (0.00%)  1/12 (8.33%)  1/13 (7.69%)  3/12 (25.00%)  6/28 (21.43%) 
Oral herpes  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Pharyngitis streptococcal  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Respiratory tract infection  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Sinusitis  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Upper respiratory tract infection  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Urinary tract infection  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  2/12 (16.67%)  1/28 (3.57%) 
Vaginitis bacterial  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Viral upper respiratory tract infection  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Vulvovaginal mycotic infection  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  1/12 (8.33%)  0/28 (0.00%) 
Injury, poisoning and procedural complications                 
Back injury  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Joint injury  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Laceration  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Muscle strain  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Post procedural complication  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Radius fracture  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Investigations                 
Alanine aminotransferase increased  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Aspartate aminotransferase increased  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Blood bilirubin increased  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Blood creatine phosphokinase increased  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Blood lactate dehydrogenase increased  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Blood pressure increased  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Blood triglycerides increased  1  2/16 (12.50%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Blood urine present  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Intraocular pressure increased  1  5/16 (31.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  2/28 (7.14%) 
Lipase increased  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Lymphocyte count decreased  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Lymphocyte percentage decreased  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Neutrophil percentage increased  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Protein urine  1  1/16 (6.25%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Weight decreased  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Metabolism and nutrition disorders                 
Gout  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Increased appetite  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  2/16 (12.50%)  1/17 (5.88%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Back pain  1  2/16 (12.50%)  1/17 (5.88%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Exostosis  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Flank pain  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Joint swelling  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Limb discomfort  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Muscle spasms  1  2/16 (12.50%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Musculoskeletal pain  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Musculoskeletal stiffness  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Myalgia  1  1/16 (6.25%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Pain in extremity  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Spondylitis  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Fibroadenoma of breast  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Nervous system disorders                 
Aphonia  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Dizziness  1  3/16 (18.75%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Headache  1  10/16 (62.50%)  4/17 (23.53%)  3/5 (60.00%)  2/4 (50.00%)  5/12 (41.67%)  3/13 (23.08%)  4/12 (33.33%)  1/28 (3.57%) 
Hyperaesthesia  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  1/28 (3.57%) 
Migraine  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Paraesthesia  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  2/28 (7.14%) 
Presyncope  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Sinus headache  1  2/16 (12.50%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Somnolence  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Syncope  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Tension headache  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  1/12 (8.33%)  1/28 (3.57%) 
Psychiatric disorders                 
Anxiety  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  2/13 (15.38%)  0/12 (0.00%)  0/28 (0.00%) 
Anxiety disorder  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Depression  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Insomnia  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  1/4 (25.00%)  0/12 (0.00%)  0/13 (0.00%)  1/12 (8.33%)  0/28 (0.00%) 
Nervousness  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Renal and urinary disorders                 
Nephrolithiasis  1  1/16 (6.25%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Reproductive system and breast disorders                 
Uterine haemorrhage  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Uterine spasm  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Cough  1  0/16 (0.00%)  2/17 (11.76%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Nasal congestion  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Oropharyngeal pain  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  1/28 (3.57%) 
Rhinorrhoea  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Sinus congestion  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Vocal cord disorder  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Skin and subcutaneous tissue disorders                 
Acne  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  1/12 (8.33%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Alopecia  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  1/28 (3.57%) 
Dermatitis acneiform  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Dermatitis contact  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  1/4 (25.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Eczema  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  0/12 (0.00%)  0/28 (0.00%) 
Madarosis  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Pruritus  1  0/16 (0.00%)  1/17 (5.88%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  1/12 (8.33%)  2/28 (7.14%) 
Pruritus generalised  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  2/12 (16.67%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Psoriasis  1  0/16 (0.00%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  2/28 (7.14%) 
Rash  1  1/16 (6.25%)  2/17 (11.76%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  1/13 (7.69%)  1/12 (8.33%)  1/28 (3.57%) 
Rash pruritic  1  0/16 (0.00%)  0/17 (0.00%)  1/5 (20.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Skin odour abnormal  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
Vascular disorders                 
Hot flush  1  1/16 (6.25%)  0/17 (0.00%)  0/5 (0.00%)  0/4 (0.00%)  0/12 (0.00%)  0/13 (0.00%)  0/12 (0.00%)  0/28 (0.00%) 
1
Term from vocabulary, MedDRA
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. However, 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
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00685399    
Other Study ID Numbers: CAIN457A2208
2011-001243-67 ( EudraCT Number )
First Submitted: May 23, 2008
First Posted: May 28, 2008
Results First Submitted: February 12, 2015
Results First Posted: July 17, 2017
Last Update Posted: July 17, 2017