Japan dose Regimen study of AZD1656 in Japanese type 2 diabetes mellitus patients

Study identifier:D1020C00016

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A 4-month treatment, Randomized, Double-blind, Placebo-Controlled, Multi-centre, Parallel-Group Phase 2 study to Evaluate Efficacy, Safety and Tolerability of Different Dosing Regimens of AZD1656 as Monotherapy in Japanese Type 2 Diabetes Mellitus Patients

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 2

Healthy volunteers

Study drug

AZD1656, Placebo

Sex

All

Actual Enrollment

224

Study type

Interventional

Age

20 Years +

Date

Study Start Date: 01 May 2010

Primary Completion Date: 01 May 2011

Study Completion Date: 01 May 2011

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Tokyo, Japan

Location

Research Site

Osaka, Japan

Location

Research Site

Suita, Japan

Arms	Assigned Interventions
Experimental: high AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	Drug: AZD1656 Oral tablet administered twice daily during 4 months
Experimental: Middle AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	Drug: AZD1656 Oral tablet administered twice daily during 4 months
Experimental: low AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Drug: AZD1656 Oral tablet administered twice daily during 4 months
Placebo Comparator: 4	Drug: Placebo administered twice daily during 4 months

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment: 224 Study Start Date: May 2010 Study Completion Date: May 2011 Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Wash-out period for patients treated with anti-diabetes treatment at enrolment.

Reporting Groups

	Description
High dose	200 mg (daily dose)
Middle Dose	140 mg (daily dose)
Low Dose	80 mg (daily dose)
Placebo	Placebo

Participant Flow: Overall Study

	High dose	Middle Dose	Low Dose	Placebo
STARTED	55	58	56	55
COMPLETED	46	52	51	50
NOT COMPLETED	9	6	5	5
Withdrawal by Subject	3	1	1	1
Protocol Violation	0	0	0	1
Adverse Event	1	1	0	0
Study-specific withdrawal criteria	1	1	2	0
Unspecified	4	3	2	3

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
High dose	200 mg (daily dose)
Middle Dose	140 mg (daily dose)
Low Dose	80 mg (daily dose)
Placebo	Placebo

Baseline Measures

	High dose	Middle Dose	Low Dose	Placebo	Total
Number of Participants [units: Participants]	55	58	56	55	224
Age Continuous [units: Years] Mean ± Standard Deviation	57 ± 9	55 ± 9	55 ± 10	57 ± 9	56 ± 9
Gender, Male/Female [units: Participants]
Female	7	8	8	9	32
Male	48	50	48	46	192

Outcome Measures

1. Primary Outcome Measure: Change in Haemoglobin A1c (HbA1c) [ Time Frame: from baseline to 4 months ]

Measure Type	Primary
Measure Name	Change in Haemoglobin A1c (HbA1c)
Measure Description
Time Frame	from baseline to 4 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High dose	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle dose	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low dose	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo dose	Placebo

Measured Values

	Arm 1 - High dose	Arm 2 - Middle dose	Arm 3 - Low dose	Arm 4 - Placebo dose
Number of Participants Analyzed [units:participants]	55	58	54	55
Change in Haemoglobin A1c (HbA1c) [units: Percentage] Mean (Standard Deviation)	0.0 (1.2)	-0.3 (1.3)	0.1 (1.2)	0.2 (0.7)

No statistical analysis provided for Change in Haemoglobin A1c (HbA1c)

2. Secondary Outcome Measure: Change in fasting plasma glucose (FPG) [ Time Frame: from baseline to 4 months ]

Measure Type	Secondary
Measure Name	Change in fasting plasma glucose (FPG)
Measure Description
Time Frame	from baseline to 4 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High dose	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle dose	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low dose	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo dose	Placebo

Measured Values

	Arm 1 - High dose	Arm 2 - Middle dose	Arm 3 - Low dose	Arm 4 - Placebo dose
Number of Participants Analyzed [units:participants]	55	58	56	55
Change in fasting plasma glucose (FPG) [units: mg/dL] Mean (Standard Deviation)	9 (42)	6 (45)	1 (36)	16 (28)

No statistical analysis provided for Change in fasting plasma glucose (FPG)

3. Secondary Outcome Measure: Number of responders in terms of HbA1C ≤ 7% [ Time Frame: at 4th month ]

Measure Type	Secondary
Measure Name	Number of responders in terms of HbA1C ≤ 7%
Measure Description
Time Frame	at 4th month
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo	Placebo

Measured Values

	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Number of Participants Analyzed [units:participants]	55	58	54	55
Number of responders in terms of HbA1C ≤ 7% [units: Participants]	7	16	7	1

No statistical analysis provided for Number of responders in terms of HbA1C ≤ 7%

4. Secondary Outcome Measure: Number of responders in terms of HbA1C ≤ 6.5% [ Time Frame: at 4th month ]

Measure Type	Secondary
Measure Name	Number of responders in terms of HbA1C ≤ 6.5%
Measure Description
Time Frame	at 4th month
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo	Placebo

Measured Values

	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Number of Participants Analyzed [units:participants]	55	58	54	55
Number of responders in terms of HbA1C ≤ 6.5% [units: Participants]	2	8	2	0

No statistical analysis provided for Number of responders in terms of HbA1C ≤ 6.5%

5. Secondary Outcome Measure: Percentage change in low-density lipoprotein cholesterol (LDL-C) [ Time Frame: from baseline to 4 months ]

Measure Type	Secondary
Measure Name	Percentage change in low-density lipoprotein cholesterol (LDL-C)
Measure Description
Time Frame	from baseline to 4 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo	Placebo

Measured Values

	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Number of Participants Analyzed [units:participants]	55	58	56	55
Percentage change in low-density lipoprotein cholesterol (LDL-C) [units: Percentage] Mean (Standard Deviation)	8.9 (19.9)	7.7 (18.8)	4.0 (15.6)	5.8 (18.4)

No statistical analysis provided for Percentage change in low-density lipoprotein cholesterol (LDL-C)

6. Secondary Outcome Measure: Percentage change in high-density lipoprotein cholesterol (HDL-C) [ Time Frame: from baseline to 4 months ]

Measure Type	Secondary
Measure Name	Percentage change in high-density lipoprotein cholesterol (HDL-C)
Measure Description
Time Frame	from baseline to 4 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo	Placebo

Measured Values

	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Number of Participants Analyzed [units:participants]	55	58	56	55
Percentage change in high-density lipoprotein cholesterol (HDL-C) [units: Percentage] Mean (Standard Deviation)	8.8 (18.0)	8.7 (12.9)	11.6 (12.7)	8.5 (12.5)

No statistical analysis provided for Percentage change in high-density lipoprotein cholesterol (HDL-C)

7. Secondary Outcome Measure: Percentage change in triglycerides [ Time Frame: from baseline to 4 months ]

Measure Type	Secondary
Measure Name	Percentage change in triglycerides
Measure Description
Time Frame	from baseline to 4 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo	Placebo

Measured Values

	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Number of Participants Analyzed [units:participants]	55	58	56	55
Percentage change in triglycerides [units: Percentage] Mean (Standard Deviation)	10.8 (44.0)	25.0 (58.5)	6.7 (29.4)	18.1 (46.8)

No statistical analysis provided for Percentage change in triglycerides

8. Secondary Outcome Measure: Change in high-sensitivity C-reactive protein (hs-CRP) [ Time Frame: from baseline to 4 months ]

Measure Type	Secondary
Measure Name	Change in high-sensitivity C-reactive protein (hs-CRP)
Measure Description
Time Frame	from baseline to 4 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population was prior to rescue treatment (FAS)

Reporting Groups

	Description
Arm 1 - High	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)
Arm 2 - Middle	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)
Arm 3 - Low	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)
Arm 4 - Placebo	Placebo

Measured Values

	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Number of Participants Analyzed [units:participants]	55	58	54	55
Change in high-sensitivity C-reactive protein (hs-CRP) [units: mg/dL] Mean (Standard Deviation)	0.058 (0.138)	0.021 (0.117)	0.033 (0.125)	-0.007 (0.115)

No statistical analysis provided for Change in high-sensitivity C-reactive protein (hs-CRP)

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
High dose	200 mg (daily dose)
Middle Dose	140 mg (daily dose)
Low Dose	80 mg (daily dose)
Placebo	Placebo

Serious Adverse Events

	High dose	Middle Dose	Low Dose	Placebo
Total, serious adverse events
# participants affected / at risk	0/22 (0.00%)	0/23 (0.00%)	0/28 (0.00%)	0/23 (0.00%)

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	3%

Reporting Groups

	Description
High dose	200 mg (daily dose)
Middle Dose	140 mg (daily dose)
Low Dose	80 mg (daily dose)
Placebo	Placebo

Other Adverse Events

High dose

Middle Dose

Low Dose

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

16/55 (29.09%)

19/58 (32.76%)

16/56 (28.57%)

16/55 (29.09%)

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

6/55 (10.91%)

9/58 (15.52%)

9/56 (16.07%)

11/55 (20.00%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

2/55 (3.64%)

1/58 (1.72%)

0/56 (0.00%)

1/55 (1.82%)

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

2/55 (3.64%)

0/58 (0.00%)

1/56 (1.79%)

1/55 (1.82%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

0/55 (0.00%)

2/58 (3.45%)

0/56 (0.00%)

0/55 (0.00%)

Musculoskeletal and connective tissue disorders

Back Pain²,^†

# participants affected / at risk

2/55 (3.64%)

1/58 (1.72%)

1/56 (1.79%)

1/55 (1.82%)

Investigations

Aspartate Aminotransferase Increased¹,^†

# participants affected / at risk

2/55 (3.64%)

2/58 (3.45%)

0/56 (0.00%)

0/55 (0.00%)

Investigations

Alanine Aminotransferase Increased¹,^†

# participants affected / at risk

1/55 (1.82%)

2/58 (3.45%)

0/56 (0.00%)

0/55 (0.00%)

Investigations

Blood Triglycerides Increased¹,^†

# participants affected / at risk

0/55 (0.00%)

2/58 (3.45%)

0/56 (0.00%)

0/55 (0.00%)

Investigations

Electrocardiogram T Wave Inversion¹,^†

# participants affected / at risk

0/55 (0.00%)

0/58 (0.00%)

2/56 (3.57%)

0/55 (0.00%)

Metabolism and nutrition disorders

Diabetes Mellitus¹,^†

# participants affected / at risk

2/55 (3.64%)

2/58 (3.45%)

1/56 (1.79%)

1/55 (1.82%)

Respiratory, thoracic and mediastinal disorders

Upper Respiratory Tract Inflammation¹,^†

# participants affected / at risk

1/55 (1.82%)

2/58 (3.45%)

2/56 (3.57%)

0/55 (0.00%)

Skin and subcutaneous tissue disorders

Eczema Asteatotic¹,^†

# participants affected / at risk

0/55 (0.00%)

0/58 (0.00%)

1/56 (1.79%)

2/55 (3.64%)

Eye disorders

Asthenopia¹,^†

# participants affected / at risk

0/55 (0.00%)

0/58 (0.00%)

2/56 (3.57%)

0/55 (0.00%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

2/55 (3.64%)

0/58 (0.00%)

1/56 (1.79%)

0/55 (0.00%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

2/55 (3.64%)

0/58 (0.00%)

0/56 (0.00%)

0/55 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 14.0
2	Term from vocabulary, MedDRA14.0
3	Term from vocabulary,

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
Phone	+44 1625 518062
E-mail:	[email protected]

Documents available

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CSP-D1020C00016.pdf
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CSR-D1020C00016.pdf
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Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Maria Leonsson-Zachrisson

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=247&filename=CSP-D1020C00016.pdf

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CSP-D1020C00016.pdf

CSR-D1020C00016.pdf

Trial Results Summaries