A Dose-Finding Study of RO4998452 in Patients With Diabetes Mellitus

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00800176
• Collaborator: (none)
• Enrollment: 394
• Locations: 67
• Arms: 6
• Actual Duration (Months): 9.2
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This 6 arm study will evaluate the efficacy, safety and pharmacokinetics of 5 doses of RO4998452 compared to placebo in patients with type 2 diabetes mellitus. Patients will be randomized to one of 6 groups to receive RO4998452 at doses of 2.5mg, 5mg, 10mg, 20mg or 40mg po daily, or placebo daily. Patients pre-treated with stable metformin will continue to take their usual dose of metformin throughout the study.The anticipated time on study treatment is <=3 months

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Type 2	Drug: Placebo; Drug: RO4998452; Drug: RO4998452; Drug: RO4998452; Drug: RO4998452; Drug: RO4998452	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 394 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Double-blind, Randomized, Parallel Group, Placebo-controlled 12-week Study to Investigate Glycemic Parameters of Efficacy, Safety/ Tolerability and Pharmacokinetics of Five Dose Levels of RO4998452 in Patients With Type 2 Diabetes Mellitus
• Actual Study Start Date: Jan 22, 2009
• Actual Primary Completion Date: Oct 28, 2009
• Actual Study Completion Date: Oct 28, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	Drug: Placebo; po daily for 12 weeks
Experimental: RO4998452 10mg During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	Drug: RO4998452; 10mg po daily for 12 weeks
Experimental: RO4998452 2.5mg During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	Drug: RO4998452; 2.5mg po daily for 12 weeks
Experimental: RO4998452 20mg During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	Drug: RO4998452; 20mg po daily for 12 weeks
Experimental: RO4998452 40mg During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.	Drug: RO4998452; 40mg po daily for 12 weeks
Experimental: RO4998452 5mg During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	Drug: RO4998452; 5mg po daily for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Absolute Change in HbA1c [Baseline, Week 4, Week 8 and Week 12]

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose (mmol/L) [Baseline and Week 12]

2. Change From Baseline in Mean Daily Glucose Concentration (mmol/L) [Baseline and Week 12]

3. Change From Baseline in Fructosamine Concentration (μmol/L) [Baseline and 12 weeks]

4. Change From Baseline in Meal Tolerance Test: 0-3h Mean Glucose Concentration (mmol/L) [Baseline and Week 12]

5. Change From Baseline in Meal Tolerance Test: 0-3h Mean Insulin Concentration (mmol/L) [Baseline and Week 12]

6. Change From Baseline in Meal Tolerance Test: 0-3h Urinary Glucose Excretion (mmol/L) [Baseline and Week 12]

7. Change From Baseline in Body Weight (kg) [Baseline and Week 12]

8. Percentage of Participants Treated to Target HbA1c < 7% [Baseline up to 12 weeks]

9. Percentage of Participants Treated to Target HbA1c < 6.5% [Baseline up to 12 weeks]

10. Percentage of Participants With at Least One Adverse Event [Baseline up to 12 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• adult patients, 18-75 years of age;

• type 2 diabetes, diagnosed for >=3 months;

• either treated with diet, exercise and stable metformin, or with diet and exercise alone.

Exclusion Criteria:

• type 1 diabetes mellitus;

• currently or within 2 months prior to screening treated with an oral or injectable anti-diabetic agent except stable doses of metformin;

• currently or within 6 months prior to screening treated with any PPARgamma agonist;

• uncontrolled hypertension;

• significant pre-diagnosed diabetic complications requiring treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States	85015
2		Los Angeles	California	United States	90057
3		Palm Springs	California	United States	92262
4		Bradenton	Florida	United States	34208
5		Jacksonville	Florida	United States	32216
6		Atlanta	Georgia	United States	30342
7		Hayden Lake	Idaho	United States	83835
8		Rochester	New York	United States	14609
9		Greensboro	North Carolina	United States	27408
10		Midland	Texas	United States	79707
11		Richmond	Virginia	United States	23294
12		Adelaide		Australia	5000
13		St. Leonards		Australia	2065
14		Fortaleza		Brazil	60120-021
15		Goiania		Brazil	74043011
16		Sao Paulo		Brazil	01244-030
17		Sao Paulo		Brazil	04022-001
18		Vancouver	British Columbia	Canada	V5Z 1L8
19		London	Ontario	Canada	NGA 4V2
20		Toronto	Ontario	Canada	M4G 3E8
21		Toronto	Ontario	Canada	M9W 4L6
22		Montreal	Quebec	Canada	H2W 1T8
23		Berlin		Germany	10115
24		Falkensee		Germany	14612
25		Luebeck		Germany	23562
26		Mainz		Germany	55116
27		Neuss		Germany	41460
28		Hong Kong		Hong Kong	852
29		Hong Kong		Hong Kong
30		Fukuoka		Japan	812-0025
31		Ibaraki		Japan	311-0113
32		Kanagawa		Japan	232-0064
33		Osaka		Japan	530-0001
34		Saitama		Japan	343-0827
35		Saitama		Japan	362-0021
36		Tokyo		Japan	160-0017
37		Tokyo		Japan	192-0071
38		Jelgava		Latvia	LV-3001
39		Riga		Latvia	1002
40		Talsi		Latvia	3200
41		Valmiera		Latvia	4201
42		Chihuahua		Mexico	31238
43		Guadalajara		Mexico	44600
44		Guadalajara		Mexico	44650
45		Mexico City		Mexico	11650
46		Alba-iulia		Romania	51077
47		Brasov		Romania	500365
48		Bucharest		Romania	020045
49		Bucharest		Romania	020475
50		Bucharest		Romania	020725
51		Bucharest		Romania
52		Targu-mures		Romania	540004
53		Moscow		Russian Federation	117049
54		Moscow		Russian Federation	119121
55		Moscow		Russian Federation	129110
56		Nizhny Novgorod		Russian Federation	603126
57		Novosibirsk		Russian Federation	630047
58		S.petersburg		Russian Federation	194017
59		Saratov		Russian Federation	410038
60		St Petersburg		Russian Federation	195257
61		St Petersburg		Russian Federation	197089
62		St Petersburg		Russian Federation	197198
63		St. Petersburg		Russian Federation	191124
64		Yaroslavl		Russian Federation	150062
65		Alzira		Spain	46600
66		Lerida		Spain	25198
67		Sevilla		Spain	41013

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00800176
• Other Study ID Numbers: BC21587; 2008-001249-24
• First Posted: Dec 2, 2008
• Last Update Posted: Nov 18, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	Screening period: Week 6 to 5 prior to randomization
Pre-assignment Detail	As soon as the results of the screening tests were available, eligible patients could start the 4-week placebo run-in period (visit week -4). A diet and exercise plan was discussed based on the recommendations of the investigator. This plan was not to be changed during the study

Arm/Group Title	Placebo	RO4998452 2.5mg	RO4998452 5mg	RO4998452 10 mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Period Title: Overall Study
STARTED	66	66	65	66	64	67
COMPLETED	57	60	65	62	60	62
NOT COMPLETED	9	6	0	4	4	5

Baseline Characteristics

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg	Total
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.	Total of all reporting groups
Overall Participants	66	66	65	66	64	67	394
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.9 (11.12)	53.3 (10.86)	54.8 (10.53)	54.5 (10.7)	56.3 (9.79)	57.5 (9.31)	55.1 (10.34)
Sex: Female, Male (Count of Participants)
Female	30 45.5%	32 48.5%	34 52.3%	32 48.5%	21 32.8%	36 53.7%	185 47%
Male	36 54.5%	34 51.5%	31 47.7%	34 51.5%	43 67.2%	31 46.3%	209 53%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	42 63.6%	46 69.7%	41 63.1%	40 60.6%	45 70.3%	39 58.2%	253 64.2%
Not Hispanic or Latino	24 36.4%	20 30.3%	24 36.9%	26 39.4%	19 29.7%	28 41.8%	141 35.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	18 27.3%	14 21.2%	14 21.5%	15 22.7%	13 20.3%	19 28.4%	93 23.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 1.5%	0 0%	1 1.5%	2 3%	2 3.1%	0 0%	6 1.5%
White	42 63.6%	46 69.7%	41 63.1%	40 60.6%	45 70.3%	39 58.2%	253 64.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	5 7.6%	6 9.1%	9 13.8%	9 13.6%	4 6.3%	9 13.4%	42 10.7%
Race/Ethnicity, Customized (Number) [Number]
Ex-Japan	54 81.8%	55 83.3%	53 81.5%	54 81.8%	53 82.8%	54 80.6%	323 82%
Japan	12 18.2%	11 16.7%	12 18.5%	12 18.2%	11 17.2%	13 19.4%	71 18%

Outcome Measures

1. Primary Outcome

Title	Absolute Change in HbA1c
Time Frame	Baseline, Week 4, Week 8 and Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	65	64	65	66	64	66
Baseline	7.872	7.939	8.006	7.998	7.919	7.933
Week 4	-0.238	-0.394	-0.460	-0.539	-0.516	-0.564
Week 8	-0.280	-0.468	-0.611	-0.694	-0.768	-0.832
Week 12	-0.269	-0.440	-0.617	-0.694	-0.768	-0.832

2. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (mmol/L)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	65	64	65	66	64	66
Baseline	8.738	8.917	8.695	8.824	8.741	8.992
Last Visit: Change from Baseline	-0.502	-0.021	-0.641	-1.042	-0.935	-1.422

3. Secondary Outcome

Title	Change From Baseline in Mean Daily Glucose Concentration (mmol/L)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	65	64	63	66	64	66
Change from Baseline	9.655	9.546	9.750	9.843	9.614	9.648
Last Visit: Absolute Change from Baseline	-0.278	-0.556	-0.800	-1.055	-0.882	-1.298

4. Secondary Outcome

Title	Change From Baseline in Fructosamine Concentration (μmol/L)
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	65	64	65	66	64	66
Baseline	293.292	294.891	292.600	290.970	292.672	305.015
Last Visit: Absolute Change from Baseline	-0.368	-11.202	-12.992	-16.712	-18.758	-20.619

5. Secondary Outcome

Title	Change From Baseline in Meal Tolerance Test: 0-3h Mean Glucose Concentration (mmol/L)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	63	63	65	66	63	65
Baseline	11.663	11.661	11.689	11.432	11.643	12.032
Last Visit: Absolute Change from Baseline	-0.655	-1.692	-2.146	-2.347	-2.443	-2.884

6. Secondary Outcome

Title	Change From Baseline in Meal Tolerance Test: 0-3h Mean Insulin Concentration (mmol/L)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	59	61	62	64	61	63
Baseline	201.243	202.269	207.255	223.964	219.396	189.286
Last Visit: Absolute Change from Baseline	-8.909	-46.108	-39.409	-68.881	-67.373	-58.053

7. Secondary Outcome

Title	Change From Baseline in Meal Tolerance Test: 0-3h Urinary Glucose Excretion (mmol/L)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	63	64	63	65	62	66
Baseline	6.607	8.472	6.841	11.659	14.039	10.395
Last Visit: Absolute Change from Baseline	-1.282	43.369	52.396	68.634	62.610	59.294

8. Secondary Outcome

Title	Change From Baseline in Body Weight (kg)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	65	64	65	66	64	66
Baseline	83.965	85.455	82.149	83.411	84.914	81.568
Last Visit: Absolute Change from Baseline	-0.741	-1.564	-1.853	-2.235	-2.551	-2.824

9. Secondary Outcome

Title	Percentage of Participants Treated to Target HbA1c < 7%
Time Frame	Baseline up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	65	64	65	66	64	66
Number (95% Confidence Interval) [Percentage]	13.8	17.2	23.1	24.2	34.4	40.9

10. Secondary Outcome

Title	Percentage of Participants Treated to Target HbA1c < 6.5%
Time Frame	Baseline up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set included all patients who were randomized, received at least one dose of study medication, and had an evaluable baseline and at least one evaluable post baseline measurement of HbA1c. If patient's HbA1c value at baseline visit was missing, latest screening HbA1c value was used as baseline. If patient received an incorrect dose of study medication at any time during study, patient was analyzed according to dose patient was randomized to, not dose patient received.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	65	64	65	66	64	66
Number (95% Confidence Interval) [Percentage]	3.1	6.3	9.2	6.1	10.9	16.7

11. Secondary Outcome

Title	Percentage of Participants With at Least One Adverse Event
Time Frame	Baseline up to 12 weeks

Outcome Measure Data

Analysis Population Description

The safety population consisted of all patients randomized and received at least one dose of double-blind study medication (DBSM). If patient received incorrect dose of DBSM throughout study, patient was analyzed according to dose actually received. If patient received an incorrect dose of DBSM for only a portion of study, patient was analyzed according to dose patient was randomized to.

Arm/Group Title	Placebo	RO4998452 2.5 mg	RO4998452 5mg	RO4998452 10mg	RO4998452 20mg	RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
Measure Participants	66	66	65	66	64	67
Number [Percentage]	37.9	36.4	46.2	37.9	35.9	46.3

Adverse Events

Time Frame	Baseline up to 8 months
Adverse Event Reporting Description	The safety population consisted of all patients randomized and received at least one dose of double-blind study medication (DBSM). If patient received incorrect dose of DBSM throughout study, patient was analyzed according to dose actually received. If patient received an incorrect dose of DBSM for only a portion of study, patient was analyzed according to dose patient was randomized to.
Arm/Group Title	Placebo		RO4998452 2.5mg		RO4998452 5mg		RO4998452 10mg		RO4998452 20mg		RO4998452 40mg
Arm/Group Description	During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test.		During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 2.5 mg of RO4998452.		During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 5 mg of RO4998452.		During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 10 mg of RO4998452.		During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 20 mg of RO4998452.		During the single-blind run-in period, two placebo capsules were taken in the morning approximately 15 minutes prior to breakfast. During the 12-week double-blind treatment period, two capsules were taken in the morning approximately 15 minutes prior to breakfast, except on the days of the meal tolerance test. The two capsules combined contained 40 mg of RO4998452.
All Cause Mortality
	Placebo		RO4998452 2.5mg		RO4998452 5mg		RO4998452 10mg		RO4998452 20mg		RO4998452 40mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		RO4998452 2.5mg		RO4998452 5mg		RO4998452 10mg		RO4998452 20mg		RO4998452 40mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/66 (1.5%)		2/66 (3%)		0/65 (0%)		0/66 (0%)		0/64 (0%)		1/67 (1.5%)
Gastrointestinal disorders
INGUINAL HERNIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
Injury, poisoning and procedural complications
ANIMAL BITE	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Nervous system disorders
CEREBRAL HAEMORRHAGE	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		RO4998452 2.5mg		RO4998452 5mg		RO4998452 10mg		RO4998452 20mg		RO4998452 40mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/66 (37.9%)		24/66 (36.4%)		30/65 (46.2%)		25/66 (37.9%)		23/64 (35.9%)		31/67 (46.3%)
Blood and lymphatic system disorders
ANAEMIA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	3/67 (4.5%)	3
IRON DEFICIENCY ANAEMIA	2/66 (3%)	2	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Cardiac disorders
ATRIOVENTRICULAR BLOCK FIRST DEGREE	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
SINUS BRADYCARDIA	1/66 (1.5%)	1	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
SINUS TACHYCARDIA	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
ANGINA PECTORIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
BUNDLE BRANCH BLOCK LEFT	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
BUNDLE BRANCH BLOCK RIGHT	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
CARDIAC FAILURE	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
MYOCARDIAL INFARCTION	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
MYOCARDIAL ISCHAEMIA	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
PALPITATIONS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
SUPRAVENTRICULAR EXTRASYSTOLES	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
Congenital, familial and genetic disorders
PHIMOSIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
TYPE II HYPERLIPIDAEMIA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
TYPE IV HYPERLIPIDAEMIA	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Endocrine disorders
HYPOTHYROIDISM	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
Eye disorders
VISION BLURRED	0/66 (0%)	0	1/66 (1.5%)	1	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
CONJUNCTIVITIS	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
DIABETIC RETINOPATHY	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
GLAUCOMA	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
OCULAR DISCOMFORT	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
OCULAR HYPERAEMIA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
VISUAL ACUITY REDUCED	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
Gastrointestinal disorders
CONSTIPATION	1/66 (1.5%)	1	1/66 (1.5%)	1	1/65 (1.5%)	1	2/66 (3%)	2	1/64 (1.6%)	1	2/67 (3%)	2
NAUSEA	1/66 (1.5%)	1	1/66 (1.5%)	1	1/65 (1.5%)	1	2/66 (3%)	2	1/64 (1.6%)	1	1/67 (1.5%)	1
TOOTHACHE	1/66 (1.5%)	1	0/66 (0%)	0	2/65 (3.1%)	2	0/66 (0%)	0	0/64 (0%)	0	2/67 (3%)	2
DIARRHOEA	1/66 (1.5%)	1	1/66 (1.5%)	1	0/65 (0%)	0	2/66 (3%)	2	0/64 (0%)	0	0/67 (0%)	0
FOOD POISONING	1/66 (1.5%)	1	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
GASTRITIS	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
GINGIVAL PAIN	1/66 (1.5%)	1	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
VOMITING	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	2/67 (3%)	2
ABDOMINAL PAIN UPPER	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
DENTAL CARIES	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
FLATULENCE	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
INGUINAL HERNIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
INTRA-ABDOMINAL HAEMATOMA	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
SALIVA ALTERED	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
General disorders
HUNGER	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	1/67 (1.5%)	1
THIRST	0/66 (0%)	0	1/66 (1.5%)	1	1/65 (1.5%)	1	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
FATIGUE	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
OEDEMA PERIPHERAL	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
ASTHENIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
INFLUENZA LIKE ILLNESS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
MALAISE	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
VESSEL PUNCTURE SITE HAEMATOMA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Hepatobiliary disorders
BILIARY COLIC	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
HEPATIC STEATOSIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
Infections and infestations
NASOPHARYNGITIS	0/66 (0%)	0	2/66 (3%)	2	1/65 (1.5%)	1	4/66 (6.1%)	4	0/64 (0%)	0	2/67 (3%)	2
URINARY TRACT INFECTION	1/66 (1.5%)	1	1/66 (1.5%)	1	2/65 (3.1%)	2	2/66 (3%)	2	0/64 (0%)	0	2/67 (3%)	2
PHARYNGITIS	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
BRONCHITIS	0/66 (0%)	0	1/66 (1.5%)	1	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
GASTROENTERITIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	2/67 (3%)	2
ORAL HERPES	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
PYELONEPHRITIS	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
UPPER RESPIRATORY TRACT INFECTION	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
VULVOVAGINAL MYCOTIC INFECTION	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
CERVICITIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
DENGUE FEVER	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
FURUNCLE	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
GASTROENTERITIS VIRAL	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
GASTROINTESTINAL INFECTION	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
GENITAL INFECTION FUNGAL	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
GENITOURINARY TRACT INFECTION	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
INFLUENZA	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
OTITIS EXTERNA BACTERIAL	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
OTITIS MEDIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
PYELONEPHRITIS ACUTE	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
RESPIRATORY TRACT INFECTION	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
RHINITIS	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
SINUSITIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
TINEA PEDIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
VIRAL INFECTION	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Injury, poisoning and procedural complications
EXCORIATION	0/66 (0%)	0	2/66 (3%)	2	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
ANIMAL BITE	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
EPICONDYLITIS	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
FALL	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
INJURY	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
JOINT SPRAIN	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
PERIORBITAL HAEMATOMA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
THERMAL BURN	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
WOUND	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
BLOOD FIBRINOGEN INCREASED	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
ELECTROCARDIOGRAM T WAVE ABNORMAL	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
BLOOD CREATININE INCREASED	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
BLOOD UREA INCREASED	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
ELECTROCARDIOGRAM QT PROLONGED	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
ELECTROCARDIOGRAM REPOLARISATION ABNORMALITY	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
ELECTROCARDIOGRAM T WAVE BIPHASIC	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
HELICOBACTER PYLORI IDENTIFICATION TEST POSITIVE	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
LYMPH NODE PALPABLE	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
URINE OUTPUT INCREASED	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
WEIGHT DECREASED	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
Metabolism and nutrition disorders
HYPOGLYCAEMIA	2/66 (3%)	2	1/66 (1.5%)	1	0/65 (0%)	0	2/66 (3%)	2	0/64 (0%)	0	0/67 (0%)	0
HYPERURICAEMIA	2/66 (3%)	2	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
DECREASED APPETITE	0/66 (0%)	0	1/66 (1.5%)	1	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
HYPERCHOLESTEROLAEMIA	1/66 (1.5%)	1	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
HYPERTRIGLYCERIDAEMIA	1/66 (1.5%)	1	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
HYPERGLYCAEMIA	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
INCREASED APPETITE	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
POLYDIPSIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
Musculoskeletal and connective tissue disorders
BACK PAIN	2/66 (3%)	2	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	1/64 (1.6%)	1	1/67 (1.5%)	1
OSTEOARTHRITIS	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	1/66 (1.5%)	1	0/64 (0%)	0	1/67 (1.5%)	1
ARTHRALGIA	0/66 (0%)	0	1/66 (1.5%)	1	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
MUSCLE SPASMS	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
MUSCULOSKELETAL PAIN	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	2/66 (3%)	2	0/64 (0%)	0	0/67 (0%)	0
NECK PAIN	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
PAIN IN EXTREMITY	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	1/67 (1.5%)	1
ARTHRITIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
INTERVERTEBRAL DISC	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
MUSCLE CONTRACTURE	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
MYALGIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
OSTEOCHONDROSIS	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Nervous system disorders
HEADACHE	2/66 (3%)	2	1/66 (1.5%)	1	1/65 (1.5%)	1	0/66 (0%)	0	3/64 (4.7%)	3	3/67 (4.5%)	3
DIZZINESS	0/66 (0%)	0	2/66 (3%)	2	0/65 (0%)	0	2/66 (3%)	2	2/64 (3.1%)	2	1/67 (1.5%)	1
DIABETIC NEUROPATHY	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
SINUS HEADACHE	1/66 (1.5%)	1	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
APHONIA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
BURNING SENSATION	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
CEREBRAL HAEMORRHAGE	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
FACIAL PALSY	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
HYPERSOMNIA	1/66 (1.5%)	1	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
NEUROPATHY PERIPHERAL	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
PARAESTHESIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
SCIATICA	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
SOMNOLENCE	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Psychiatric disorders
ANXIETY	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	2/66 (3%)	2	0/64 (0%)	0	0/67 (0%)	0
INSOMNIA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
AGITATION	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
DEPRESSED MOOD	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
DEPRESSION	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
LIBIDO DECREASED	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
LOSS OF LIBIDO	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Renal and urinary disorders
POLLAKIURIA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	3/66 (4.5%)	3	0/64 (0%)	0	2/67 (3%)	2
HAEMATURIA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
MICTURITION URGENCY	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
NOCTURIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
POLYURIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
RENAL COLIC	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
RENAL FAILURE ACUTE	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
RENAL IMPAIRMENT	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
MENORRHAGIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
METRORRHAGIA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
PRURITUS GENITAL	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
VULVOVAGINAL PRURITUS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	1/67 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN	2/66 (3%)	2	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
COUGH	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
ASTHMA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
NASAL CONGESTION	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
RHINORRHOEA	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
UPPER RESPIRATORY TRACT INFLAMMATION	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Skin and subcutaneous tissue disorders
DERMATITIS ALLERGIC	1/66 (1.5%)	1	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
ECZEMA	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
HYPERHIDROSIS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
RASH ERYTHEMATOUS	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
RASH MACULAR	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
RASH PRURITIC	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
SKIN EROSION	0/66 (0%)	0	0/66 (0%)	0	1/65 (1.5%)	1	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
SKIN ULCER	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	1	0/67 (0%)	0
Surgical and medical procedures
DENTAL IMPLANTATION	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	0/67 (0%)	0
TOOTH EXTRACTION	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
Vascular disorders
HYPERTENSION	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	1/66 (1.5%)	1	0/64 (0%)	0	1/67 (1.5%)	1
HOT FLUSH	0/66 (0%)	0	1/66 (1.5%)	1	0/65 (0%)	0	0/66 (0%)	0	0/64 (0%)	0	0/67 (0%)	0
HYPOTENSION	0/66 (0%)	0	0/66 (0%)	0	0/65 (0%)	0	0/66 (0%)	0	1/64 (1.6%)	11	0/67 (0%)	0

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.