Evaluate Safety as Mono or Combination Therapies With Anti-diabetes Mellitus Drugs in Japanese Subjects With Type 2 Diabetes Mellitus

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01294436
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 728
• Locations: 39
• Arm: 1
• Duration (Months): 19
• Patients Per Site: 18.7
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This is a long term, single arm, open label study to evaluate the safety and efficacy of dapagliflozin as monotherapy or in combination therapy with other anti diabetic drug in Japanese subjects with type 2 diabetes mellitus who have inadequate blood sugar control on diet and exercise or on other anti-diabetic treatment will be included in this study.

Condition or Disease	Intervention/Treatment	Phase
Type2 Diabetes; High Blood Sugar	Drug: Dapagliflozin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 728 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long Term Open Label Study to Evaluate the Safety and Efficacy of Dapagliflozin as Monotherapy or Combination Therapies With Anti-diabetic Drugs in Japanese Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open label treatment	Drug: Dapagliflozin; Oral Dose 5 or 10 mg

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With Adverse Events [Long-term treatment up to 52 weeks]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to adverse events

2. Proportion of Participants With Serious Adverse Events [Long-term treatment up to 52 weeks]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to serious adverse events

3. Proportion of Participants With At Least One Episode of Hypoglycemia [Long-term treatment up to 52 weeks]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to occurrence of hypoglycemia

4. Mean Change in Hematocrit [Baseline to Week 52]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in hematocrit

5. Mean Change in Alanine Aminotransferase (ALT) [Baseline to Week 52]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in alanine aminotransferase

6. Mean Change in Aspartate Aminotransferase (AST) [Baseline to Week 52]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in aspartate aminotransferase

7. Mean Change in Blood Urea Nitrogen (BUN) [Baseline to Week 52]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood urea nitrogen

8. Mean Change in Magnesium [Baseline to Week 52]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in magnesium (1 mEq/L equivalent to 0.50 mmol/L)

9. Mean Change in Serum Uric Acid [Baseline to Week 52]

   To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in serum uric acid

10. Mean Change in Seated Heart Rate [Baseline to Week 52]

    To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in pulse

11. Mean Change in Seated Diastolic Blood Pressure [Baseline to Week 52]

    To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure

12. Mean Change in Seated Systolic Blood Pressure [Baseline to Week 52]

    To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure

Other Outcome Measures

1. Mean Change in HbA1c Levels [Baseline to Week 52]

   To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in HbA1c

2. Mean Change in Body Weight [Baseline to Week 52]

   To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in body weight

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures

• Men or women age ≥20 years old (Either gender needs to be 40% or higher of total number of treated subjects)

• diagnosed with type2 DM ; ≥6.5% and ≤10% at 1 week before treatment started

Exclusion Criteria:

• Type 1 diabetes mellitus,

• FPG >240 mg/dL before treatment started

• Subjects who have history of unstable or rapidly progressing renal disease

• Subjects who have severe hepatic insufficiency and/or significant abnormal liver function

• Significant cardiovascular history

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Nagoya	Aichi	Japan
2	Research Site	Owariasahi	Aichi	Japan
3	Research Site	Toyohashi	Aichi	Japan
4	Research Site	Hirosaki	Aomori	Japan
5	Research Site	Niihama	Ehime	Japan
6	Research Site	Itoshima	Fukuoka	Japan
7	Research Site	Yukuhashi	Fukuoka	Japan
8	Research Site	Annaka	Gunma	Japan
9	Research Site	OTA	Gunma	Japan
10	Research Site	Aki-gun	Hiroshima	Japan
11	Research Site	Sapporo	Hokkaido	Japan
12	Research Site	Sanuki	Kagawa	Japan
13	Research Site	Takamatsu	Kagawa	Japan
14	Research Site	Kamakura	Kanagawa	Japan
15	Research Site	Kawasaki	Kanagawa	Japan
16	Research Site	Yokohamashi	Kanagawa	Japan
17	Research Site	Yokohama	Kanagawa	Japan
18	Research Site	Zushi	Kanagawa	Japan
19	Research Site	Sendai	Miyagi	Japan
20	Research Site	Matsumoto	Nagano	Japan
21	Research Site	Suita	Osaka	Japan
22	Research Site	Otsu	Shiga	Japan
23	Research Site	Atami	Shizuoka	Japan
24	Research Site	Komatsushima	Tokushima	Japan
25	Research Site	Chiyoda	Tokyo	Japan
26	Research Site	Chuo	Tokyo	Japan
27	Research Site	Mitaka	Tokyo	Japan
28	Research Site	OTA	Tokyo	Japan
29	Research Site	Shibuya	Tokyo	Japan
30	Research Site	Shinjuku	Tokyo	Japan
31	Research Site	Taito	Tokyo	Japan
32	Research Site	Takaoka	Toyama	Japan
33	Research Site	UBE	Yamaguchi	Japan
34	Research Site	Fukuoka		Japan
35	Research Site	Hiroshima		Japan
36	Research Site	Kochi		Japan
37	Research Site	Osaka		Japan
38	Research Site	Shizuoka		Japan
39	Research Site	Toyama		Japan

Sponsors and Collaborators

• AstraZeneca
• Bristol-Myers Squibb

Investigators

• Study Director: Dr Jisin Yang, MD, AstraZeneca KK

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01294436
• Other Study ID Numbers: D1692C00012
• First Posted: Feb 11, 2011
• Last Update Posted: Dec 17, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by AstraZeneca: Phase3; Clinical trial; Type 2 Diabetes Mellitus
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Hyperglycemia; Dapagliflozin

Study Results

Participant Flow

Recruitment Details	First subject enrolled: 28-Feb-2011; Last subject last visit: 15-Sep-2012; 1030 participants were enrolled in 56 Japanese centers. 728 Japanese men and women aged >=20 years with inadequate glycemic control (HbA1c levels of 6.5% to 10.0% prior to study treatment) with diet and exercise were treated.
Pre-assignment Detail	A 6-week wash-out period was applicable only for subjects with ongoing anti-diabetic treatment at enrolment. A 4-week lead-in period was applicable for all subjects.

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Period Title: Overall Study
STARTED	249	479
COMPLETED	221	409
NOT COMPLETED	28	70

Baseline Characteristics

Arm/Group Title	Monotherapy	All Combination Therapies	Total
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs	Total of all reporting groups
Overall Participants	249	479	728
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (10.40)	57.2 (10.06)	57.5 (10.18)
Age, Customized (participants) [Number]
< 65 years	182 73.1%	365 76.2%	547 75.1%
65 - <75 years	55 22.1%	102 21.3%	157 21.6%
>= 75 years	12 4.8%	12 2.5%	24 3.3%
Sex: Female, Male (Count of Participants)
Female	103 41.4%	211 44.1%	314 43.1%
Male	146 58.6%	268 55.9%	414 56.9%
Region of Enrollment (participants) [Number]
Japan	249 100%	479 100%	728 100%
Body Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	67.77 (13.437)	67.40 (14.529)	67.52 (14.157)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.72 (4.196)	25.61 (4.440)	25.64 (4.355)
Seated Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	127.5 (13.73)	125.8 (14.13)	126.4 (14.01)
HbA1c (Percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent]	7.53 (0.761)	7.82 (0.865)	7.72 (0.842)
Fasting Plasma Glucose (FPG) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	140.29 (25.355)	147.35 (29.097)	144.93 (28.057)

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Adverse Events
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to adverse events
Time Frame	Long-term treatment up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	249	479
Number [Percentage of participants]	79.1 31.8%	72.4 15.1%

2. Primary Outcome

Title	Proportion of Participants With Serious Adverse Events
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to serious adverse events
Time Frame	Long-term treatment up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	249	479
Number [Percentage of participants]	5.6 2.2%	3.1 0.6%

3. Primary Outcome

Title	Proportion of Participants With At Least One Episode of Hypoglycemia
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to occurrence of hypoglycemia
Time Frame	Long-term treatment up to 52 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	249	479
Number [Percentage of participants]	2.4 1%	4.0 0.8%

4. Primary Outcome

Title	Mean Change in Hematocrit
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in hematocrit
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Error) [Percent]	2.17 (0.1396)	2.00 (0.1115)

5. Primary Outcome

Title	Mean Change in Alanine Aminotransferase (ALT)
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in alanine aminotransferase
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Error) [U/L]	-7.1 (0.955)	-5.4 (0.622)

6. Primary Outcome

Title	Mean Change in Aspartate Aminotransferase (AST)
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in aspartate aminotransferase
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	405
Mean (Standard Error) [U/L]	-3.9 (0.695)	-2.6 (0.410)

7. Primary Outcome

Title	Mean Change in Blood Urea Nitrogen (BUN)
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood urea nitrogen
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Error) [mg/dL]	2.4 (0.250)	2.3 (0.168)

8. Primary Outcome

Title	Mean Change in Magnesium
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in magnesium (1 mEq/L equivalent to 0.50 mmol/L)
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Error) [mEq/L]	0.05 (0.0074)	0.05 (0.0064)

9. Primary Outcome

Title	Mean Change in Serum Uric Acid
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in serum uric acid
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Error) [mg/dL]	-0.61 (0.0578)	-0.50 (0.0374)

10. Primary Outcome

Title	Mean Change in Seated Heart Rate
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in pulse
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Deviation) [beats per minute (bpm)]	-0.4 (7.52)	0.2 (7.95)

11. Primary Outcome

Title	Mean Change in Seated Diastolic Blood Pressure
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Deviation) [mmHg]	-2.9 (8.16)	-2.1 (8.73)

12. Primary Outcome

Title	Mean Change in Seated Systolic Blood Pressure
Description	To evaluate the safety and tolerability of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in blood pressure
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Analysis Set, participants with non-missing baseline and week 52 values

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	220	407
Mean (Standard Deviation) [mmHg]	-5.2 (11.68)	-3.9 (13.03)

13. Other Pre-specified Outcome

Title	Mean Change in HbA1c Levels
Description	To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in HbA1c
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set, participants with non-missing baseline and week 52 (LOCF) value

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	249	477
Mean (95% Confidence Interval) [Percent]	-0.66 (11.68)	-0.68 (13.03)

14. Other Pre-specified Outcome

Title	Mean Change in Body Weight
Description	To evaluate the efficacy of long-term treatment up to 52 weeks with the dosing regimen of dapagliflozin, where it started with 5 mg and titrated up to 10 mg depending on participant's condition of glycemic control, in regard to the change in body weight
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set, participants with non-missing baseline and week 52 (LOCF) value

Arm/Group Title	Monotherapy	All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only	Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
Measure Participants	249	477
Mean (95% Confidence Interval) [kg]	-2.58 (11.68)	-2.06 (13.03)

Adverse Events

Time Frame	Non-serious / serious adverse events on or after the first day and on or prior to the last day of the 52-week open-label treatment period plus 4/30 days or up to follow-up visit if earlier.
Adverse Event Reporting Description	Participants were questioned at each study visit about the occurrence of any health problems and any examination conducted at a study visit was assessed in comparison to the status at study entry.
Arm/Group Title	Monotherapy		All Combination Therapies
Arm/Group Description	Dapagliflozin 5/10 mg only		Dapagliflozin 5/10 mg in combination with any anti-diabetic drugs
All Cause Mortality
	Monotherapy		All Combination Therapies
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Monotherapy		All Combination Therapies
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/249 (5.6%)		15/479 (3.1%)
Cardiac disorders
TACHYCARDIA PAROXYSMAL	0/249 (0%)		1/479 (0.2%)
Ear and labyrinth disorders
VERTIGO POSITIONAL	0/249 (0%)		1/479 (0.2%)
Eye disorders
AGE RELATED MACULAR DEGENERATION	1/249 (0.4%)		0/479 (0%)
CATARACT	1/249 (0.4%)		1/479 (0.2%)
RETINAL DETACHMENT	1/249 (0.4%)		0/479 (0%)
Gastrointestinal disorders
COLONIC POLYP	2/249 (0.8%)		0/479 (0%)
GASTROINTESTINAL INFLAMMATION	0/249 (0%)		1/479 (0.2%)
HAEMORRHOIDS	0/249 (0%)		1/479 (0.2%)
Hepatobiliary disorders
CHOLELITHIASIS	0/249 (0%)		1/479 (0.2%)
Infections and infestations
CHRONIC SINUSITIS	1/249 (0.4%)		0/479 (0%)
DIVERTICULITIS	1/249 (0.4%)		0/479 (0%)
GASTROENTERITIS	0/249 (0%)		1/479 (0.2%)
LOBAR PNEUMONIA	0/249 (0%)		1/479 (0.2%)
PHARYNGITIS	0/249 (0%)		1/479 (0.2%)
Injury, poisoning and procedural complications
LIMB TRAUMATIC AMPUTATION	1/249 (0.4%)		0/479 (0%)
SPINAL COMPRESSION FRACTURE	0/249 (0%)		1/479 (0.2%)
Investigations
ELECTROCARDIOGRAM ABNORMAL	0/249 (0%)		1/479 (0.2%)
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS	1/249 (0.4%)		0/479 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER	2/249 (0.8%)		0/479 (0%)
BREAST CANCER	1/249 (0.4%)		0/479 (0%)
RECTAL CANCER	0/249 (0%)		1/479 (0.2%)
Nervous system disorders
BRAIN STEM HAEMORRHAGE	1/249 (0.4%)		0/479 (0%)
DIZZINESS	1/249 (0.4%)		0/479 (0%)
CEREBRAL INFARCTION	0/249 (0%)		3/479 (0.6%)
Renal and urinary disorders
CALCULUS URINARY	0/249 (0%)		1/479 (0.2%)
Other (Not Including Serious) Adverse Events
	Monotherapy		All Combination Therapies
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/249 (28.5%)		126/479 (26.3%)
Infections and infestations
NASOPHARYNGITIS	63/249 (25.3%)		116/479 (24.2%)
Renal and urinary disorders
POLLAKIURIA	13/249 (5.2%)		13/479 (2.7%)

Limitations/Caveats

In the efficacy analysis, for participants who did not complete 52-week treatment period LOCF (last observation carried forward) was used.

More Information

Certain Agreements

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

If an Investigator requests permission to publish data from this study any such publication is to be agreed with AstraZeneca (AZ) in advance. The investigator agrees to provide AZ as soon as possible with drafts of proposed publications. Unless otherwise agreed, AZ shall have a period of 60 days from receipt of the proposed final manuscript to review it and may within such time require that submission for publication of the manuscript be delayed in order for AZ to file patent applications.