A Study to Assess the Efficacy of RO5459072 in Participants With Primary Sjogren's Syndrome

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02701985
• Collaborator: (none)
• Enrollment: 75
• Locations: 31
• Arms: 2
• Actual Duration (Months): 12.2
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, two-treatment arm, parallel-group study designed to evaluate the effects of RO5459072 treatment on disease activity and symptoms of Sjogren's syndrome in adult participants with moderate to severe primary Sjogren's syndrome. The total duration of the study for each participant will be approximately 18 weeks (including screening).

Condition or Disease	Intervention/Treatment	Phase
Sjogren's Syndrome	Drug: Placebo; Drug: RO5459072	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Phase 2A Study to Assess the Efficacy of RO5459072 in Patients With Primary Sjogren's Syndrome
• Actual Study Start Date: Jul 5, 2016
• Actual Primary Completion Date: Jul 10, 2017
• Actual Study Completion Date: Jul 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Matching-placebo capsules will be administered orally, 2 times a day, for up to 12 weeks.	Drug: Placebo; Matching-placebo capsules will be administered orally, 2 times a day with food.
Experimental: RO5459072 RO5459072 at a dose of 100 milligrams (as capsules) will be administered orally, 2 times a day, for up to 12 weeks.	Drug: RO5459072; RO5459072 at a dose of 100 milligrams (as capsules) will be administered orally, 2 times a day with food.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Clinically Relevant Decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score [12 weeks]

   Percentage of participants with a clinically relevant decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score is defined as participants with absolute decrease of ≥ 3-points in ESSDAI score. ESSDAI is physician-assessed disease activity index developed by EULAR consortium consisting of 44 items in 12 organ-specific 'domains' (constitutional,lymphadenopathy, articular,muscular,cutaneous,glandular,pulmonary,renal,peripheral nervous system,central nervous system,hematological,biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A score ≥ 5 is considered moderate or severe disease activity and a clinically relevant change in ESSDAI score is defined as absolute decrease of ≥ 3-points.

Secondary Outcome Measures

1. Percentage of Participants With a Clinically Relevant Decrease in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score [12 weeks]

   The efficacy of RO5459072 in patients with primary Sjogren's Syndrome Disease is evaluated in terms of the percentage of participants with a clinically relevant decrease in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score, where a clinically relevant decrease in ESSPRI score is defined as a decrease of ≥ 1 point. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains where all domains carry same weight.

2. Change From Baseline in ESSDAI Score at Week 12 [Baseline (Week -1), Week 12]

   Change from baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSDAI is a physician-assessed disease activity index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 44 items in 12 organ-specific 'domains' contributing to disease activity (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. An overall score is then calculated as the sum of all individual weighted domain scores. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity).

3. Change From Baseline in ESSPRI Score at Week 12 [Baseline (Week -1), Week 12]

   Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight.

4. Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Score at Week 12 [Baseline (Week -1), Week 12]

   Change from baseline in Short Form-36 Health Survey (SF-36) Mental score is defined as the change in score between baseline (Week -1) and Week 12. The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (general health, physical functioning, role-functioning physical, bodily pain, social functioning, role-functioning emotional, mental health, and vitality), with each domain scoring on a scale 0-100 (a score of 0 = maximum disability and a score of 100 = no disability). Reported here is the mental health domain score.

5. Change From Baseline in SF-36 Physical Score at Week 12 [Baseline (Week -1), Week 12]

   Change from baseline in Short Form-36 Health Survey (SF-36) Physical Score is defined as the change in score between baseline (Week -1) and Week 12. The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (general health, physical functioning, role-functioning physical, bodily pain, social functioning, role-functioning emotional, mental health, and vitality), with each domain scoring on a scale 0-100. (a score of 0 = maximum disability and a score of 100 = no disability)

6. Change From Baseline in ESSPRI Dryness Component Score at Week 12 [Baseline (Week -1), Week 12]

   Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) dryness component score is defined as the change in score between baseline (Week -1) and Week 12. The Dryness Component score ranged from 0-10 (0 =no symptom at all and 10 = worst symptom imaginable).

7. Change From Baseline in ESSPRI Fatigue Component Score at Week 12 [Baseline (Week -1), Week 12]

   Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) fatigue component score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI score consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable).

8. Change From Baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Pain Component Score at Week 12 [Baseline (Week -1), Week 12]

   Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) pain component score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI score consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (Each domain scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable).

9. Change From Baseline in Tear Flow Rate at Weeks 2, 6, and 12 [Baseline, Week 2, Week 6, and Week 12]

   Un-stimulated tear production rate was measured from both eyes (without the use of analgesics/ anesthetic drops) at baseline and at on-treatment visits using the Schirmer method. A thin strip of filter paper (Schirmer strip, e.g., 35 x 5 mm) was placed at the junction of the lateral and middle thirds of the lower eyelid of each eye. The maximum length of wetting along the strip at the end of the test period was measured.

10. Change From Baseline in Mechanically Stimulated Salivary Flow Rate at Weeks 2, 6, and 12 [Baseline, Week 2, Week 6, and Week 12]

    Change from baseline in mechanically stimulated salivary flow rate is defined as the change in flow (mL/min) between baseline (Week -1) and Week 2, Week 6 and Week 12. Using a mechanical stimulation method of a piece of neutral wax, paraffin, silicone, unflavored chewing gum, or similar chewable, unflavored, nonabsorbent material, patients were instructed to chew for a period of 5 minutes. The stimulated salivary flow rate was calculated assuming a specific gravity of 1 (i.e., 1 mL saliva = 1 g) and expressed in mL per minute.

11. Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen A at Weeks 6, and 12 [Baseline, Week 6, and Week 12]

    Anti-Sjögren's-syndrome-related antigen A is a type of antibody found in the auto-antibody titers.

12. Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen B at Weeks 6, and 12 [Baseline, Week 6, and Week 12]

    Anti-Sjögren's-syndrome-related antigen B is a type of antibody found in the auto-antibody titers.

13. Change From Baseline in Rheumatoid Factor at Weeks 6, and 12 [Baseline, Week 6, and Week 12]

    Rheumatoid factor is a type of auto-antibody found in the auto-antibody titers.

14. Change From Baseline in Total Immunoglobulin G (IgG) at Weeks 6, and 12 [Baseline, Week 6, and Week 12]

    Total IgG is a type of auto-antibody found in the auto-antibody titers.

15. Change From Baseline in Total Immunoglobulin M (IgM) at Weeks 6, and 12 [Baseline, Week 6, and Week 12]

    Total IgM is a type of auto-antibody found in the auto-antibody titers.

16. Minimum Concentration (Cmin) of RO5459072 [Week 2, Week 6, and Week 12]

    Minimum observed plasma concentration (mass/volume)

17. Maximum Concentration (Cmax) of RO5459072 [Week 2, Week 6, and Week 12]

    Maximum observed plasma concentration (mass/volume)

18. Average Concentration (Caverage) of RO5459072 [Week 2, Week 6, and Week 12]

    Average observed plasma concentration (mass/volume)

19. Percentage of Participants With Adverse Events [Baseline up to Week 14]

    An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A diagnosis of primary Sjogren's syndrome according to the revised American-European Consensus Group (AECG) criteria

• ESSDAI score greater than or equal to (>/=) 5

• ESSPRI score >/=5

• Elevated serum titers of anti-Sjogren's-syndrome-related antigen A (anti-SSA) and/or anti-Sjogren's-syndrome-related antigen B (anti-SSB) antibodies at screening

• Negative pregnancy test at screening and baseline (for women only)

• Willing to comply with the study procedures and restrictions, including measures to prevent pregnancy and restrictions on sperm donation

Exclusion Criteria:

• A diagnosis of secondary Sjogren's syndrome according to the revised AECG criteria

• Severe complications of Sjogren's syndrome

• Systemic immunosuppressant therapy, cyclophosphamide, or B-cell depleting therapy within 6 months prior to the screening visit

• Corticosteroid therapy exceeding 7.5 mg prednisone equivalents per day

• A positive test result for hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV), or tuberculosis, or any other active viral, fungal, yeast or bacterial infection at screening

• A history suggesting reduced immune function or any other conditions predisposing participants to serious infection

• A history of lymphoma, myeloma or monoclonal gammopathy of unknown significance (MGUS), or any other malignancies within the past 5 years

• A diagnosis of fibromyalgia or significant depression

• Having any concomitant disease or condition that could interfere with the conduct of the study, or that would pose an unacceptable risk to the individual

• Participation in an investigational drug or device study within 3 months prior to screening

• Inability to comply with the study protocol for any other reason

• Women who are lactating, breastfeeding or planning to nurse

• Using other prohibited medication (moderate or potent inhibitors of CYP3A4; strong inducers of CYP3A4; strong inhibitors of the transporter P-glycoprotein [P-gp]; sensitive substrates of CYP3A4 with a narrow therapeutic index)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wallace Rheumatic Study Center	Beverly Hills	California	United States	90211
2	Denver Arthritis Clinic	Denver	Colorado	United States	80230-7127
3	Ochsner Clinic Foundation	Baton Rouge	Louisiana	United States	70809
4	John Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224
5	University Of Michigan	Ann Arbor	Michigan	United States	48109
6	Winthrop University Hospital	Mineola	New York	United States	11501
7	Shanahan Rheumatology & Immunology, PLLC	Raleigh	North Carolina	United States	27617
8	MetroHealth System	Cleveland	Ohio	United States	44109
9	Altoona Center For Clinical Research	Duncansville	Pennsylvania	United States	16635
10	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
11	Clinical Research Center of Reading	Wyomissing	Pennsylvania	United States	19610
12	Ramesh Gupta - PP	Memphis	Tennessee	United States	38119
13	Hopital Avicenne, Paris	Bobigny		France	93009
14	C.H.U. Ambroise Pare (AP-HP)	Boulogne Billancourt		France	92104
15	Hopital La Cavale Blanche; Rhumatologie	Brest		France	29609
16	Hopital Lapeyronie; Immunologie Rhumatologie	Montpellier		France	34295
17	Charité Research Organisation GmbH	Berlin		Germany	10117
18	Szpital Uniwersytecki; nr 2 im. Dr J. Biziela; Klinika Reumatologii i Ukladowych Chorob	Bydgoszcz		Poland	85-168
19	MedPolonia	Poznan		Poland	60-693
20	Niepubliczny Opieki Zdrowotnej; Reumatika - Ctr Reum.	Warszawa		Poland	02-691
21	Centrum Medyczne AMED	Warszawa		Poland	03-291
22	Instituto Portugues de Reumatologia	Lisboa		Portugal	1050-34
23	Centro Hospitalar de Lisboa Norte, EPE - Hospital Santa Maria	Lisboa		Portugal	1649-035
24	Centro Hospitalar do Porto - Hospital de Santo António	Porto		Portugal	4099-001
25	Centro Hospitalar de Sao Joao,E.P.E.	Porto		Portugal	4200-319
26	University Hospitals Birmingham NHS Foundation Trust	Birmingham		United Kingdom	B15 2TH
27	Barts and the London NHS Trust	London		United Kingdom	E1 2ES
28	University College London Hospitals NHS Foundation Trust - University College Hospital	London		United Kingdom	NW1 2PG
29	The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne		United Kingdom	NE1 4LP
30	Sheffield Teaching Hospitals NHS Foundation Trust; Royal Hallamshire Hospital	Sheffield		United Kingdom	S10 2JF
31	Great Western Hospitals NHS Foundation Trust.	Wiltshire		United Kingdom	SN3 6BB

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 30, 2016

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02701985
• Other Study ID Numbers: BP30037; 2015-004476-30
• First Posted: Mar 8, 2016
• Last Update Posted: Aug 1, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Sjogren's Syndrome; Syndrome; Petesicatib

Study Results

Participant Flow

Pre-assignment Detail	A total of 75 patients were randomized in a 1:1 ratio to RO5459072 or placebo (38 patients in the RO5459072 treatment group and 37 patients in the placebo group).

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Period Title: Overall Study
STARTED	37	38
COMPLETED	34	32
NOT COMPLETED	3	6

Baseline Characteristics

Arm/Group Title	Placebo	RO5459072	Total
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.	Total of all reporting groups
Overall Participants	37	38	75
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.3 (11.8)	52.1 (13.2)	52.2 (12.5)
Sex: Female, Male (Count of Participants)
Female	36 97.3%	32 84.2%	68 90.7%
Male	1 2.7%	6 15.8%	7 9.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.4%	0 0%	2 2.7%
Not Hispanic or Latino	35 94.6%	38 100%	73 97.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.7%	1 2.6%	2 2.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 8.1%	2 5.3%	5 6.7%
White	33 89.2%	35 92.1%	68 90.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Clinically Relevant Decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score
Description	Percentage of participants with a clinically relevant decrease in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score is defined as participants with absolute decrease of ≥ 3-points in ESSDAI score. ESSDAI is physician-assessed disease activity index developed by EULAR consortium consisting of 44 items in 12 organ-specific 'domains' (constitutional,lymphadenopathy, articular,muscular,cutaneous,glandular,pulmonary,renal,peripheral nervous system,central nervous system,hematological,biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A score ≥ 5 is considered moderate or severe disease activity and a clinically relevant change in ESSDAI score is defined as absolute decrease of ≥ 3-points.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Number (95% Confidence Interval) [Percentage of Participants]	37.8 102.2%	42.1 110.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	The proportion of patients who have ≥ 3 point reduction from baseline in ESSDAI score after 12 weeks of treatment was compared between the two treatment arms using a Pearson Chi-square test (two sided p-values, alpha 0.05). The difference in proportions and corresponding 95% confidence interval (CI) are provided. Patients with missing data at Week 12 will be treated as non-responders in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7955
	Comments
	Method	Chi-square with Schouten Correction
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	4.27
	Confidence Interval	(2-Sided) 95%; -20.55 to 29.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With a Clinically Relevant Decrease in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score
Description	The efficacy of RO5459072 in patients with primary Sjogren's Syndrome Disease is evaluated in terms of the percentage of participants with a clinically relevant decrease in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score, where a clinically relevant decrease in ESSPRI score is defined as a decrease of ≥ 1 point. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains where all domains carry same weight.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measument of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Number (95% Confidence Interval) [Percentage of Participants]	56.8 153.5%	57.9 152.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	The proportion of patients who have ≥ 1 point reduction from baseline in ESSPRI score after 12 weeks of treatment was compared between the two treatment arms using a Pearson Chi-square test (two sided p-values, alpha 0.05). The difference in proportions and corresponding 95% CI are provided. Patients with missing data at Week 12 will be treated as non-responders in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9877
	Comments
	Method	Chi-square with Schouten Correction
	Comments
Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; -23.92 to 26.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in ESSDAI Score at Week 12
Description	Change from baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSDAI is a physician-assessed disease activity index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 44 items in 12 organ-specific 'domains' contributing to disease activity (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. An overall score is then calculated as the sum of all individual weighted domain scores. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity).
Time Frame	Baseline (Week -1), Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline in ESSDAI Score	11.27 (5.71)	11.79 (4.69)
Change From Baseline in ESSDAI Score at Week 12	-3.06 (3.96)	-3.25 (4.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	A Mixed Model for Repeated Measures (MMRM) approach incorporating all observed data up to 12 weeks of treatment was used. The MMRM included the absolute change from baseline as the dependent variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8905
	Comments
	Method	Mixed Model for Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -2.04 to 1.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in ESSPRI Score at Week 12
Description	Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight.
Time Frame	Baseline (Week -1), Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline in ESSPRI Score	7.34 (1.19)	6.98 (0.98)
Change From Baseline in ESSPRI Score at Week 12	-1.35 (1.67)	-1.51 (1.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	A Mixed Model for Repeated Measures (MMRM) approach incorporating all observed data up to 12 weeks of treatment was used. The MMRM included the absolute change from baseline as the dependent variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6077
	Comments
	Method	Mixed Model of Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -1.08 to 0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Short Form 36 Health Survey (SF-36) Mental Score at Week 12
Description	Change from baseline in Short Form-36 Health Survey (SF-36) Mental score is defined as the change in score between baseline (Week -1) and Week 12. The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (general health, physical functioning, role-functioning physical, bodily pain, social functioning, role-functioning emotional, mental health, and vitality), with each domain scoring on a scale 0-100 (a score of 0 = maximum disability and a score of 100 = no disability). Reported here is the mental health domain score.
Time Frame	Baseline (Week -1), Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline	42.09 (11.18)	40.52 (9.27)
Change from Baseline at Week 12	4.52 (7.15)	3.02 (9.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	A Mixed Model for Repeated Measures (MMRM) approach incorporating all observed data up to 12 weeks of treatment was used. The MMRM included the absolute change from baseline as the dependent variable
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2846
	Comments
	Method	Mixed Model of Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-2.06
	Confidence Interval	() 95%; -5.87 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in SF-36 Physical Score at Week 12
Description	Change from baseline in Short Form-36 Health Survey (SF-36) Physical Score is defined as the change in score between baseline (Week -1) and Week 12. The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (general health, physical functioning, role-functioning physical, bodily pain, social functioning, role-functioning emotional, mental health, and vitality), with each domain scoring on a scale 0-100. (a score of 0 = maximum disability and a score of 100 = no disability)
Time Frame	Baseline (Week -1), Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline in SF-36 Physical Score	40.86 (6.82)	40.71 (6.94)
Change From Baseline at Week 12	2.46 (6.09)	3.01 (5.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	A Mixed Model for Repeated Measures (MMRM) approach incorporating all observed data up to 12 weeks of treatment was used. The MMRM included the absolute change from baseline as the dependent variable
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8134
	Comments
	Method	Mixed Model of Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Difference in Adjusted Means
	Estimated Value	-0.33
	Confidence Interval	() 95%; -2.43 to 3.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in ESSPRI Dryness Component Score at Week 12
Description	Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) dryness component score is defined as the change in score between baseline (Week -1) and Week 12. The Dryness Component score ranged from 0-10 (0 =no symptom at all and 10 = worst symptom imaginable).
Time Frame	Baseline (Week -1), Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline	7.54 (1.57)	7.45 (1.25)
Change From Baseline at Week 12	-1.15 (1.56)	-1.77 (2.29)

8. Secondary Outcome

Title	Change From Baseline in ESSPRI Fatigue Component Score at Week 12
Description	Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) fatigue component score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI score consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable).
Time Frame	Baseline (Week -1), Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline	7.22 (1.81)	7.24 (1.84)
Change From Baseline at Week 12	-1.29 (2.24)	-1.94 (2.16)

9. Secondary Outcome

Title	Change From Baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Pain Component Score at Week 12
Description	Change from baseline in EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) pain component score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI score consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (Each domain scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable).
Time Frame	Baseline (Week -1), Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline	7.27 (1.71)	6.26 (2.05)
Change From Baseline at Week 12	-1.62 (2.70)	-0.97 (2.56)

10. Secondary Outcome

Title	Change From Baseline in Tear Flow Rate at Weeks 2, 6, and 12
Description	Un-stimulated tear production rate was measured from both eyes (without the use of analgesics/ anesthetic drops) at baseline and at on-treatment visits using the Schirmer method. A thin strip of filter paper (Schirmer strip, e.g., 35 x 5 mm) was placed at the junction of the lateral and middle thirds of the lower eyelid of each eye. The maximum length of wetting along the strip at the end of the test period was measured.
Time Frame	Baseline, Week 2, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline in Tear Flow Rate	7.53 (9.66)	7.84 (10.15)
Change from Baseline at Week 2	-0.54 (5.02)	-0.81 (5.06)
Change from Baseline at Week 6	-1.39 (6.32)	-0.95 (7.95)
Change from Baseline at Week 12	-2.38 (6.47)	-1.65 (7.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	A Mixed Model for Repeated Measures (MMRM) approach incorporating all observed data up to 12 weeks of treatment was used. The MMRM included the absolute change from baseline as the dependent variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4266
	Comments
	Method	Mixed Model of Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.87
	Confidence Interval	() 95%; -1.30 to 3.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Mechanically Stimulated Salivary Flow Rate at Weeks 2, 6, and 12
Description	Change from baseline in mechanically stimulated salivary flow rate is defined as the change in flow (mL/min) between baseline (Week -1) and Week 2, Week 6 and Week 12. Using a mechanical stimulation method of a piece of neutral wax, paraffin, silicone, unflavored chewing gum, or similar chewable, unflavored, nonabsorbent material, patients were instructed to chew for a period of 5 minutes. The stimulated salivary flow rate was calculated assuming a specific gravity of 1 (i.e., 1 mL saliva = 1 g) and expressed in mL per minute.
Time Frame	Baseline, Week 2, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

mITT population was defined as all randomized participants, who received any study medication and had evaluable measurement of the parameter of interest at baseline and at least one post-baseline visit.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline	0.45 (0.29)	0.55 (0.58)
Change from Baseline at Week 2	0.10 (0.33)	-0.01 (0.33)
Change from Baseline at Week 6	0.10 (0.31)	0.11 (0.47)
Change from Baseline at Week 12	0.12 (0.30)	0.24 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, RO5459072
	Comments	A Mixed Model for Repeated Measures (MMRM) approach incorporating all observed data up to 12 weeks of treatment was used. The MMRM included the absolute change from baseline as the dependent variable.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6429
	Comments
	Method	Mixed Model of Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	() 95%; -0.21 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen A at Weeks 6, and 12
Description	Anti-Sjögren's-syndrome-related antigen A is a type of antibody found in the auto-antibody titers.
Time Frame	Baseline, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline	214.52 (58.06)	217.78 (53.96)
Change from Baseline at Week 6	-4.82 (16.05)	-1.47 (13.90)
Change from Baseline at Week 12	-2.57 (18.97)	-5.20 (11.65)

13. Secondary Outcome

Title	Change From Baseline in Anti-Sjögren's-Syndrome-Related Antigen B at Weeks 6, and 12
Description	Anti-Sjögren's-syndrome-related antigen B is a type of antibody found in the auto-antibody titers.
Time Frame	Baseline, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline	101.66 (130.48)	76.94 (120.76)
Change from Baseline at Week 6	1.94 (15.20)	-2.55 (13.09)
Change from Baseline at Week 12	1.35 (13.52)	-4.47 (12.32)

14. Secondary Outcome

Title	Change From Baseline in Rheumatoid Factor at Weeks 6, and 12
Description	Rheumatoid factor is a type of auto-antibody found in the auto-antibody titers.
Time Frame	Baseline, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline in Rheumatoid Factor	43.00 (48.51)	117.84 (336.82)
Change from Baseline at Week 6	-1.50 (10.74)	-28.03 (70.04)
Change from Baseline at Week 12	-0.68 (9.97)	-57.77 (173.75)

15. Secondary Outcome

Title	Change From Baseline in Total Immunoglobulin G (IgG) at Weeks 6, and 12
Description	Total IgG is a type of auto-antibody found in the auto-antibody titers.
Time Frame	Baseline, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline in Total IgG	15.74 (6.77)	13.59 (4.92)
Change from Baseline at Week 6	0.11 (1.51)	-0.30 (1.21)
Change from Baseline at Week 12	0.48 (1.78)	-0.50 (1.13)

16. Secondary Outcome

Title	Change From Baseline in Total Immunoglobulin M (IgM) at Weeks 6, and 12
Description	Total IgM is a type of auto-antibody found in the auto-antibody titers.
Time Frame	Baseline, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Baseline in Total IgM	1.24 (0.82)	1.26 (0.75)
Change from Baseline at Week 6	0.03 (0.20)	-0.10 (0.17)
Change from Baseline at Week 12	0.06 (0.25)	-0.17 (0.20)

17. Secondary Outcome

Title	Minimum Concentration (Cmin) of RO5459072
Description	Minimum observed plasma concentration (mass/volume)
Time Frame	Week 2, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	RO5459072
Arm/Group Description	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	38
Median (90% Confidence Interval) [ng/mL]	1340

18. Secondary Outcome

Title	Maximum Concentration (Cmax) of RO5459072
Description	Maximum observed plasma concentration (mass/volume)
Time Frame	Week 2, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	RO5459072
Arm/Group Description	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	38
Median (90% Confidence Interval) [ng/mL]	2350

19. Secondary Outcome

Title	Average Concentration (Caverage) of RO5459072
Description	Average observed plasma concentration (mass/volume)
Time Frame	Week 2, Week 6, and Week 12

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	RO5459072
Arm/Group Description	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	38
Median (90% Confidence Interval) [ng/mL]	1740

20. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Baseline up to Week 14

Outcome Measure Data

Analysis Population Description

The safety population included all participants, who received at least one dose of the study medication. Participants were grouped according to the treatment actually received.

Arm/Group Title	Placebo	RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.	RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
Measure Participants	37	38
Number [Percentage of participants]	78.4 211.9%	76.3 200.8%

Adverse Events

Time Frame	The total duration of the study for each patient was (up to) 19 weeks.
Adverse Event Reporting Description	The safety population is defined as all patients who received at least one dose of the study medication.
Arm/Group Title	Placebo		RO5459072
Arm/Group Description	Matching-placebo capsules was administered orally, 2 times a day, for up to 12 weeks.		RO5459072 at a dose of 100 milligrams (as capsules) was administered orally, 2 times a day, for up to 12 weeks.
All Cause Mortality
	Placebo		RO5459072
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/37 (2.7%)		0/38 (0%)
Serious Adverse Events
	Placebo		RO5459072
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/37 (5.4%)		1/38 (2.6%)
Blood and lymphatic system disorders
Iron Deficiency Anaemia	0/37 (0%)	0	1/38 (2.6%)	1
Cardiac disorders
Cardiac Arrest	1/37 (2.7%)	1	0/38 (0%)	0
Metabolism and nutrition disorders
Metabolic Acidosis	1/37 (2.7%)	1	0/38 (0%)	0
Nervous system disorders
Headache	1/37 (2.7%)	1	0/38 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		RO5459072
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/37 (51.4%)		25/38 (65.8%)
Gastrointestinal disorders
Abdominal Pain	1/37 (2.7%)		3/38 (7.9%)
Diarrhoea	2/37 (5.4%)		2/38 (5.3%)
Dyspepsia	2/37 (5.4%)		0/38 (0%)
Nausea	0/37 (0%)		5/38 (13.2%)
General disorders
Fatigue	1/37 (2.7%)		2/38 (5.3%)
Pyrexia	2/37 (5.4%)		0/38 (0%)
Infections and infestations
Bronchitis	2/37 (5.4%)		1/38 (2.6%)
Influenza	1/37 (2.7%)		2/38 (5.3%)
Sinusitis	3/37 (8.1%)		1/38 (2.6%)
Upper Respiratory Tract Infection	2/37 (5.4%)		5/38 (13.2%)
Viral Upper Respiratory Tract Infection	2/37 (5.4%)		6/38 (15.8%)
Investigations
Blood Thyroid Stimulating Hormone Decreased	0/37 (0%)		2/38 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/37 (2.7%)		3/38 (7.9%)
Nervous system disorders
Headache	4/37 (10.8%)		5/38 (13.2%)
Skin and subcutaneous tissue disorders
Eczema	0/37 (0%)		2/38 (5.3%)
Pruritus	2/37 (5.4%)		2/38 (5.3%)
Rash	1/37 (2.7%)		5/38 (13.2%)
Urticaria	0/37 (0%)		5/38 (13.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.