Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus (TD2M) Patients

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01020123
• Collaborator: (none)
• Enrollment: 530
• Locations: 76
• Arms: 7
• Duration (Months): 16
• Patients Per Site: 7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary aim is to evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in TD2M Patients

Condition or Disease	Intervention/Treatment	Phase
Type II Diabetes Mellitus	Drug: AZD1656; Drug: Placebo; Drug: Glipizide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 530 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 4-month, Randomized, Double-blind, Placebo- and Active-Controlled, Multi-centre, Parallel-Group Study, With an Optional 2-month Extension, to Evaluate Efficacy, Safety and Tolerability of AZD1656 as Add-on Treatment to Metformin in Type 2 Diabetes Mellitus Patients
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 AZD1656	Drug: AZD1656; Different doses of AZD1656 administered to 5 groups of patients
Experimental: 2 AZD1656	Drug: AZD1656; Different doses of AZD1656 administered to 5 groups of patients
Experimental: 3 AZD1656	Drug: AZD1656; Different doses of AZD1656 administered to 5 groups of patients
Experimental: 4 AZD1656	Drug: AZD1656; Different doses of AZD1656 administered to 5 groups of patients
Experimental: 5 AZD1656	Drug: AZD1656; Different doses of AZD1656 administered to 5 groups of patients
Placebo Comparator: 6	Drug: Placebo; AZD1656 placebo and glipizide placebo administered to 1 group of patients
Active Comparator: 7 Glipizide administered to 1 group of patients	Drug: Glipizide; Glipizide administered to 1 group of patients

Outcome Measures

Primary Outcome Measures

1. HbA1c: Change From Baseline to 4 Month [Baseline to 4th Month]

   AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue

Secondary Outcome Measures

1. FPG: to Evaluate Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue. [baseline to 4 month]

   AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.

2. SMPG: Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue. [baseline to 4 month]

   AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.

3. OGTT/Plasma Glucose [baseline to 4 month]

   The relative change in AUC

4. OGTT/Insulin [baseline to 4 month]

   The Relative Change in AUC FAS Prior to Rescue

5. OGTT/C-peptide [baseline to 4 month]

   The relative change, FAS prior to rescue

6. OGTT/Pro-insulin/Insulin [baseline to 4 month]

   The relative change, FAS prior to rescue

7. HbA1c ≤ 7 [baseline to 4 month]

   Number of responders ≤ 7, FAS prior to rescue.

8. HbA1c ≤ 6.5 [baseline to 4 month]

   Number of Responders ≤ 6.5, FAS Prior to Rescue

9. LDL-C: Mean Ratio [baseline to 4 month]

   Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.

10. HDL-C: Change From Baseline [baseline to 4 month]

    Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.

11. Total Cholesterol: Change From Baseline [baseline to 4 month]

    Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.

12. Triglycerides: Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

13. C-reactive Protein: Change From Baseline [baseline to 4 month]

    Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI

14. Systolic Blood Pressure, Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

15. Diastolic Blood Pressure, Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

16. Pulse, Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

17. Weight, Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

18. QTcF; Electorcardiagram Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

19. Haemoglobin; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

20. Leukocytes; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

21. Sodium; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

22. Potassium; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

23. Creatinine; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

24. ALT; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

25. AST; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

26. Alkaline Phosphatase; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

27. Bilirubin; Change From Baseline [baseline to 4 month]

    Summary statistic of change from baseline

28. CL/F to Characterise the PK Properties of AZD1656. [at 4 month]

    The value is calculated using an allometric model (of a patient weighting 75 kg). The value is independent treatment given.

29. EC50 to Characterise the PD Properties of AZD1656. [at 4 month]

    The value is model based. The value is independent treatment given.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• female of non-childbearing potential

• Treated with maximally tolerated dose of metformin (≥ 1500mg/day) for at least 10 weeks prior to enrolment.

• Patients with HbA1c ≥ 7.5 but ≤ 10% at enrolment visit (Visit 1) can enter cohort 1.Patients with HbA1c between >10 % and <12 % can enter the open-label arm with AZD1656 (cohort 2)

Exclusion Criteria:

• Significant cardiovascular event within the last 6 months prior to enrolment or heart failure New York Heart Association (NYHA) class III-IV.

• Impaired renal function in terms of GFR<60 ml/min, based on Modification of Diet in Renal Disease Study Group (MDRD) calculation.

• Use of warfarin or amiodarone within 3 months prior to enrolment (screening) and use of potent CYP450 inhibitors, eg, ketoconazole and/or macrolide antibiotics within 14 days before randomisation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Temuco	Novena Region	Chile
2	Research Site	Brentwood	TN	Chile
3	Research Site	Santiago		Chile
4	Research Site	Temuco		Chile
5	Research Site	Dresden	SN	Germany
6	Research Site	Brentwood	TN	Germany
7	Research Site	Aschaffenburg		Germany
8	Research Site	Berlin		Germany
9	Research Site	Bochum		Germany
10	Research Site	Dortmund		Germany
11	Research Site	Frankfurt		Germany
12	Research Site	Görlitz		Germany
13	Research Site	Hamburg		Germany
14	Research Site	Lubeck		Germany
15	Research Site	Magdeburg		Germany
16	Research Site	St. Laurent	QC	Hungary
17	Research Site	Balatonfured		Hungary
18	Research Site	Bekescsaba		Hungary
19	Research Site	Dunaujvaros		Hungary
20	Research Site	Eger		Hungary
21	Research Site	Gyula		Hungary
22	Research Site	Kaposvar		Hungary
23	Research Site	Nyiregyhaza		Hungary
24	Research Site	Szekszard		Hungary
25	Research Site	Szigetvar		Hungary
26	Research Site	Zalaegerszeg		Hungary
27	Research Site	Brentwood	TN	Latvia
28	Research Site	Daugavpils		Latvia
29	Research Site	Jekabpils		Latvia
30	Research Site	Jelgava		Latvia
31	Research Site	Limbazi		Latvia
32	Research Site	Riga		Latvia
33	Research Site	Talsi		Latvia
34	Research Site	Valmiera		Latvia
35	Research Site	Brentwood	TN	Lithuania
36	Research Site	Kaunas		Lithuania
37	Research Site	Zapopan	Jalisco	Mexico
38	Research Site	Cuernavaca	Morelos	Mexico
39	Research Site	Monterrey	Nuevo Leon	Mexico
40	Research Site	Brentwood	TN	Mexico
41	Research Site	Meridas	Yucatan	Mexico
42	Research Site	Merida	Yucatan	Mexico
43	Research Site	Aguascalientes		Mexico
44	Research Site	Chiuahua		Mexico
45	Research Site	Monterrey		Mexico
46	Research Site	San Luis Potosi		Mexico
47	Research Site	Brentwood	TN	Peru
48	Research Site	Callao		Peru
49	Research Site	Lambayeque		Peru
50	Research Site	Lima		Peru
51	Research Site	Piura		Peru
52	Research Site	Trujillo		Peru
53	Research Site	Brentwood	TN	Poland
54	Research Site	Gdansk		Poland
55	Research Site	Krakow		Poland
56	Research Site	Kutno		Poland
57	Research Site	Wroclaw		Poland
58	Research Site	Alba Iulia	Alba	Romania
59	Research Site	Tg Mures	Mures	Romania
60	Research Site	Brentwood	TN	Romania
61	Research Site	Galati		Romania
62	Research Site	Ploiesti		Romania
63	Research Site	Sibiu		Romania
64	Research Site	Timisoara		Romania
65	Research Site	Brentwood	TN	Sweden
66	Research Site	Huddinge		Sweden
67	Research Site	Lund		Sweden
68	Research Site	Paignton	Devon	United Kingdom
69	Research Site	Liverpool	Merseyside	United Kingdom
70	Research Site	St. Laurent	QC	United Kingdom
71	Research Site	Cardiff		United Kingdom
72	Research Site	Chorley		United Kingdom
73	Research Site	Glasgow		United Kingdom
74	Research Site	Stevenage		United Kingdom
75	Research Site	West Bromwich		United Kingdom
76	Research Site	West Lothian		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Eva Johnsson, AstraZeneca R&D Mölndal
• Principal Investigator: John Wilding, DM FRCP, University Hospital Aintree

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01020123
• Other Study ID Numbers: D1020C00009
• First Posted: Nov 25, 2009
• Last Update Posted: Nov 26, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by AstraZeneca: Type II Diabetes Mellitus; metformin; glipizide
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Glipizide

Study Results

Participant Flow

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Period Title: Main Period
STARTED	93	91	52	40	88	94	72
COMPLETED	76	77	44	33	77	83	61
NOT COMPLETED	17	14	8	7	11	11	11
Period Title: Main Period
STARTED	40	35	19	13	31	38	19
COMPLETED	37	33	17	12	31	36	18
NOT COMPLETED	3	2	2	1	0	2	1

Baseline Characteristics

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label	Total
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose	Total of all reporting groups
Overall Participants	93	91	52	40	88	94	72	530
Age (Year) [Mean (Full Range) ]
Mean (Full Range) [Year]	57.1	57.1	54.4	57.4	56.9	57.1	53.1	56
Sex: Female, Male (Count of Participants)
Female	47 50.5%	46 50.5%	22 42.3%	19 47.5%	45 51.1%	46 48.9%	37 51.4%	262 49.4%
Male	46 49.5%	45 49.5%	30 57.7%	21 52.5%	43 48.9%	48 51.1%	35 48.6%	268 50.6%

Outcome Measures

1. Primary Outcome

Title	HbA1c: Change From Baseline to 4 Month
Description	AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue
Time Frame	Baseline to 4th Month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the LOCF values (see table 27 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	80	82	47	34	82
Mean (95% Confidence Interval) [Percentage]	-1.25 (-1.14)	-1.26 (-1.14)	-0.67 (-0.62)	-0.61 (-0.60)	-0.45 (NA)

2. Secondary Outcome

Title	FPG: to Evaluate Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue.
Description	AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the LOCF values (see table 29 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	90	87	49	39	85
Mean (95% Confidence Interval) [mmol/L]	-0.818 (-1.373)	-1.08 (-1.642)	0.041 (-0.652)	0.024 (-0.737)	-0.182 (NA)

3. Secondary Outcome

Title	SMPG: Change From Baseline to 4 Month, Compared With Placebo, FAS Prior to Rescue.
Description	AZD1656 is analyzed in a ANCOVA model (Glipized and Open Label is Not Included in the model), FAS Prior to Rescue.
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the LOCF values (see table 31 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	58	63	38	26	57
Mean (95% Confidence Interval) [mmol/L]	-1.596 (-2.206)	-1.557 (-2.155)	-0.874 (-1.586)	-0.604 (-1.437)	-0.213 (NA)

4. Secondary Outcome

Title	OGTT/Plasma Glucose
Description	The relative change in AUC
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the LOCF values (see table 142 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	17	13	7	8	17
Geometric Mean (95% Confidence Interval) [ratio]	0.92	0.84	1.02	0.99	0.99

5. Secondary Outcome

Title	OGTT/Insulin
Description	The Relative Change in AUC FAS Prior to Rescue
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the LOCF values (see table 146 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	16	12	6	10	16
Geometric Mean (95% Confidence Interval) [ratio]	0.81	1.08	0.97	0.90	0.91

6. Secondary Outcome

Title	OGTT/C-peptide
Description	The relative change, FAS prior to rescue
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the LOCF values (see table 150 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	17	13	7	10	16
Geometric Mean (95% Confidence Interval) [ratio]	0.97	1.11	0.90	0.95	1.00

7. Secondary Outcome

Title	OGTT/Pro-insulin/Insulin
Description	The relative change, FAS prior to rescue
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the LOCF values (see table 154 in CSR)The first 50% of patients enrolled in the study were supposed to undertake OGTT, actual number participating was 52%. However, more than 60% of the OGTT patients were excluded from the analyses, as their measurements did not comply with the protocol

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	16	12	6	10	14
Geometric Mean (95% Confidence Interval) [Ratio]	1.496	1.199	1.248	1.431	1.185

8. Secondary Outcome

Title	HbA1c ≤ 7
Description	Number of responders ≤ 7, FAS prior to rescue.
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is FAS prior to rescue, using the observed cases (see table 35 in CSR).

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	74	73	38	32	69	78	48
Number [Participants]	43 46.2%	43 47.3%	14 26.9%	11 27.5%	16 18.2%	50 53.2%	24 33.3%

9. Secondary Outcome

Title	HbA1c ≤ 6.5
Description	Number of Responders ≤ 6.5, FAS Prior to Rescue
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 228 in CSR).

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	74	73	38	32	69	78	48
Number [Participants]	35 37.6%	27 29.7%	9 17.3%	4 10%	9 10.2%	30 31.9%	16 22.2%

10. Secondary Outcome

Title	LDL-C: Mean Ratio
Description	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 228 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	74	75	43	33	73
Geometric Mean (95% Confidence Interval) [ratio]	1.07 (29.5)	1.02 (20.6)	1.07 (38.5)	1.04 (23.1)	1.02 (19.3)

11. Secondary Outcome

Title	HDL-C: Change From Baseline
Description	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 230 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	75	76	43	33	74
Geometric Mean (95% Confidence Interval) [ratio]	1.06 (6.2)	1.06 (5.1)	1.05 (7.8)	1.03 (4.1)	1.03 (5.3)

12. Secondary Outcome

Title	Total Cholesterol: Change From Baseline
Description	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI.
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 232 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	75	76	43	33	74
Geometric Mean (95% Confidence Interval) [ratio]	1.09 (36.9)	1.08 (60.2)	1.07 (41.6)	1.04 (25.3)	1.03 (26.0)

13. Secondary Outcome

Title	Triglycerides: Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 226 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	75	43	33	74	82	58
Mean (Standard Deviation) [mg/dL]	40.9 (115.3)	38.7 (99.3)	19.8 (185.3)	4.4 (49.3)	13.7 (139.4)	18.7 (152.8)	29.8 (174.3)

14. Secondary Outcome

Title	C-reactive Protein: Change From Baseline
Description	Geometric mean ratio (safety analysis set, regardless of rescue) and a 95 % CI
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 234 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin
Measure Participants	75	76	43	33	75
Geometric Mean (95% Confidence Interval) [ratio]	0.30 (0.88)	0.08 (0.86)	0.09 (0.99)	0.06 (0.74)	-0.02 (0.75)

15. Secondary Outcome

Title	Systolic Blood Pressure, Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 237 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	73	38	32	69	79	58
Mean (Standard Deviation) [mmHg]	-0.4 (12.6)	0.4 (9.9)	5.7 (11.3)	0.1 (12.6)	-0.2 (13.7)	-1.1 (13.5)	-0.3 (11.7)

16. Secondary Outcome

Title	Diastolic Blood Pressure, Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 240 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	73	38	32	69	79	58
Mean (Standard Deviation) [mmHg]	1.1 (8.6)	1.4 (8.5)	1.3 (9.1)	-0.9 (10.8)	-0.3 (8.5)	-0.1 (7.2)	0.5 (7.7)

17. Secondary Outcome

Title	Pulse, Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 236 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	73	38	32	69	79	58
Mean (Standard Deviation) [Beats/min]	0.4 (8.8)	1.6 (7.9)	1.3 (7.9)	0.3 (9.1)	-1.1 (9.4)	-0.4 (11.6)	1.3 (8.5)

18. Secondary Outcome

Title	Weight, Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 244 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	73	38	32	69	79	48
Mean (Standard Deviation) [kg]	-0.3 (2.5)	-0.6 (2.9)	-1.2 (2.7)	-1.4 (2.3)	-1.0 (2.5)	1.0 (3.4)	-0.4 (4.4)

19. Secondary Outcome

Title	QTcF; Electorcardiagram Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 258 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	74	76	43	34	77	83	63
Mean (Standard Deviation) [msec]	4.4 (15.6)	4.0 (14.5)	-2.6 (12.6)	3.8 (17.9)	2.2 (13.8)	2.7 (21.5)	1.6 (16.4)

20. Secondary Outcome

Title	Haemoglobin; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

population is safety analysis set regardless of rescue, using the observed cases (see table 197 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	76	77	44	32	76	83	61
Mean (Standard Deviation) [g/dL]	-0.20 (0.68)	-0.18 (0.62)	0.00 (0.63)	-0.11 (0.69)	-0.20 (0.71)	0.02 (0.69)	-0.25 (0.76)

21. Secondary Outcome

Title	Leukocytes; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 198 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	76	77	44	32	76	83	61
Mean (Standard Deviation) [*10^3 cells/µL]	0.39 (1.29)	0.34 (1.59)	0.35 (1.41)	-0.15 (1.09)	-0.8 (1.09)	0.27 (1.43)	-40 (1.31)

22. Secondary Outcome

Title	Sodium; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 215 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	77	44	33	76	83	60
Mean (Standard Deviation) [mEq/L]	-0.6 (2.4)	-0.7 (2.4)	-0.4 (3.0)	-0.1 (2.6)	0.0 (2.6)	-0.6 (3.3)	0.5 (2.6)

23. Secondary Outcome

Title	Potassium; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 214 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	77	43	32	75	82	58
Mean (Standard Deviation) [mEq/L]	0.02 (0.45)	-0.02 (0.26)	0.00 (0.35)	-0.01 (0.29)	-0.02 (0.34)	0.07 (0.39)	0.05 (0.38)

24. Secondary Outcome

Title	Creatinine; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 211 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	77	43	32	75	82	59
Mean (Standard Deviation) [IU/L]	0.4 (70.5)	-9.9 (87.8)	8.5 (88.7)	-8.3 (39.1)	-0.1 (32.2)	15.9 (67.1)	-7.3 (47)

25. Secondary Outcome

Title	ALT; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 206 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	76	43	32	75	82	59
Mean (Standard Deviation) [IU/L]	2.0 (12.0)	1.7 (14.8)	3.2 (17.7)	-1.8 (-1.8)	-0.4 (11.3)	2.0 (15.3)	-0.4 (15.5)

26. Secondary Outcome

Title	AST; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 207 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	76	43	32	75	82	59
Mean (Standard Deviation) [IU/L]	2.4 (9.8)	2.0 (11.0)	2.8 (13.1)	-0.6 (8.9)	-0.1 (7.9)	2.1 (13.3)	2.7 (9.6)

27. Secondary Outcome

Title	Alkaline Phosphatase; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 208 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	77	44	33	76	83	59
Mean (Standard Deviation) [IU/L]	3.8 (17.5)	-1.3 (13.3)	0.0 (13.6)	-1.8 (11.9)	-3.4 (11.5)	-4.2 (16.7)	-11.7 (24.7)

28. Secondary Outcome

Title	Bilirubin; Change From Baseline
Description	Summary statistic of change from baseline
Time Frame	baseline to 4 month

Outcome Measure Data

Analysis Population Description

The population is safety analysis set regardless of rescue, using the observed cases (see table 209 in CSR)

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Placebo	Glipizide	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Placebo add on to metformin	5-20 mg Glipizide add on to metformin, titrated dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	75	77	44	33	76	83	59
Mean (Standard Deviation) [mg/dL]	-0.02 (0.17)	-0.06 (0.21)	0.02 (0.13)	-0.05 (0.20)	-0.01 (0.20)	-0.07 (0.20)	-11.7 (24.7)

29. Secondary Outcome

Title	CL/F to Characterise the PK Properties of AZD1656.
Description	The value is calculated using an allometric model (of a patient weighting 75 kg). The value is independent treatment given.
Time Frame	at 4 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	86	87	49	39	70
Mean (Standard Error) [L/h]	9.29 (3.7)	9.29 (3.7)	9.29 (3.7)	9.29 (3.7)	9.29 (3.7)

30. Secondary Outcome

Title	EC50 to Characterise the PD Properties of AZD1656.
Description	The value is model based. The value is independent treatment given.
Time Frame	at 4 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Higher Dose	Lower Dose	40 mg Fixed Dose	20 mg Fixed Dose	Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose	10-140 mg AZD1656 add on to metformin, titrated dose	40 mg AZD1656 add on to metformin, fixed dose	20 mg AZD1656 add on to metformin, fixed dose	Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
Measure Participants	86	87	49	39	70
Mean (Standard Error) [nmol/L]	60.2 (14)	60.2 (14)	60.1 (14)	60.2 (14)	60.2 (14)

Adverse Events

Time Frame	Baseline - 6 month
Adverse Event Reporting Description	Safety was collected in 6 month
Arm/Group Title	Higher Dose		Lower Dose		40 mg Fixed Dose		20 mg Fixed Dose		Placebo		Glipizide		Open Label
Arm/Group Description	20-200 mg AZD1656 add on to metformin, titrated dose		10-140 mg AZD1656 add on to metformin, titrated dose		40 mg AZD1656 add on to metformin, fixed dose		20 mg AZD1656 add on to metformin, fixed dose		Placebo add on to metformin		5-20 mg Glipizide add on to metformin, titrated dose		Open label, 20-200 mg AZD1656 add on to metformin, titrated dose
All Cause Mortality
	Higher Dose		Lower Dose		40 mg Fixed Dose		20 mg Fixed Dose		Placebo		Glipizide		Open Label
	Affected / at Risk (%)	# Events	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)		/ (NaN)
Serious Adverse Events
	Higher Dose		Lower Dose		40 mg Fixed Dose		20 mg Fixed Dose		Placebo		Glipizide		Open Label
	Affected / at Risk (%)	# Events	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	2/92 (2.2%)		1/90 (1.1%)		1/50 (2%)		1/40 (2.5%)		2/87 (2.3%)		3/93 (3.2%)		1/71 (1.4%)
Cardiac disorders
Angina Unstable	0/92 (0%)	0	0/90 (0%)	0	0/50 (0%)	0	1/40 (2.5%)	1	0/87 (0%)	0	0/93 (0%)	0	0/71 (0%)	0
Acute myocardial infarction	0/92 (0%)	0	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	1/93 (1.1%)	1	0/71 (0%)	0
Angina pectoris	0/92 (0%)	0	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	1/93 (1.1%)	1	0/71 (0%)	0
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic	0/92 (0%)	0	0/90 (0%)	0	1/50 (2%)	1	0/40 (0%)	0	0/87 (0%)	0	0/93 (0%)	0	0/71 (0%)	0
Infections and infestations
Anal abscess	0/92 (0%)	0	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	0/93 (0%)	0	1/71 (1.4%)	1
Injury, poisoning and procedural complications
Subdural haematoma	0/92 (0%)	0	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	1/87 (1.1%)	1	0/93 (0%)	0	0/71 (0%)	0
Investigations
Blood Creatine Phosphokinase Increased	1/92 (1.1%)	1	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	0/93 (0%)	0	0/71 (0%)	0
Metabolism and nutrition disorders
Diabetic foot	0/92 (0%)	0	1/90 (1.1%)	1	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	0/93 (0%)	0	0/71 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	0/92 (0%)	0	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	1/93 (1.1%)	1	0/71 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/92 (1.1%)	1	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	0/93 (0%)	0	0/71 (0%)	0
Renal and urinary disorders
Renal failur acute	0/92 (0%)	0	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	1/87 (1.1%)	1	0/93 (0%)	0	0/71 (0%)	0
Vascular disorders
Hypertensive emergency	1/92 (1.1%)	1	0/90 (0%)	0	0/50 (0%)	0	0/40 (0%)	0	0/87 (0%)	0	0/93 (0%)	1	0/71 (0%)	0
Other (Not Including Serious) Adverse Events
	Higher Dose		Lower Dose		40 mg Fixed Dose		20 mg Fixed Dose		Placebo		Glipizide		Open Label
	Affected / at Risk (%)	# Events	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	22/92 (23.9%)		36/90 (40%)		20/50 (40%)		10/40 (25%)		14/87 (16.1%)		35/93 (37.6%)		9/71 (12.7%)
Gastrointestinal disorders
Diarrhoea	4/92 (4.3%)		7/90 (7.8%)		3/50 (6%)		3/40 (7.5%)		3/87 (3.4%)		3/93 (3.2%)		0/71 (0%)
Nausea	2/92 (2.2%)		2/90 (2.2%)		4/50 (8%)		0/40 (0%)		1/87 (1.1%)		1/93 (1.1%)		1/71 (1.4%)
Vomiting	0/92 (0%)		2/90 (2.2%)		5/50 (10%)		0/40 (0%)		0/87 (0%)		1/93 (1.1%)		0/71 (0%)
Gastritis	1/92 (1.1%)		1/90 (1.1%)		1/50 (2%)		2/40 (5%)		0/87 (0%)		2/93 (2.2%)		0/71 (0%)
General disorders
Asthenia	2/92 (2.2%)		4/90 (4.4%)		1/50 (2%)		0/40 (0%)		0/87 (0%)		7/93 (7.5%)		0/71 (0%)
Infections and infestations
Nasopharyngitis	4/92 (4.3%)		9/90 (10%)		2/50 (4%)		1/40 (2.5%)		6/87 (6.9%)		3/93 (3.2%)		3/71 (4.2%)
Gastroenteritis	2/92 (2.2%)		0/90 (0%)		0/50 (0%)		2/40 (5%)		2/87 (2.3%)		0/93 (0%)		0/71 (0%)
Nervous system disorders
Tremor	4/92 (4.3%)		4/90 (4.4%)		1/50 (2%)		1/40 (2.5%)		0/87 (0%)		10/93 (10.8%)		1/71 (1.4%)
Dizziness	2/92 (2.2%)		3/90 (3.3%)		2/50 (4%)		0/40 (0%)		2/87 (2.3%)		6/93 (6.5%)		2/71 (2.8%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/92 (1.1%)		4/90 (4.4%)		1/50 (2%)		1/40 (2.5%)		0/87 (0%)		10/93 (10.8%)		2/71 (2.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.