Japan Dose Regimen Study of AZD1656 in Japanese Type 2 Diabetes Mellitus Patients

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01152385
• Collaborator: (none)
• Enrollment: 224
• Locations: 3
• Arms: 4
• Duration (Months): 12
• Patients Per Site: 74.7
• Patients Per Site Per Month: 6.2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effect on glucose control of 3 different AZD1656 dosing regimens with placebo in Japanese type 2 diabetes mellitus (T2DM) patients, as evaluated by the change in HbA1c from baseline to the end of treatment at 4 months.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 224 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Change in Haemoglobin A1c (HbA1c) [from baseline to 4 months]

Secondary Outcome Measures

1. Change in Fasting Plasma Glucose (FPG) [from baseline to 4 months]

2. Number of Responders in Terms of HbA1C ≤ 7% [at 4th month]

3. Number of Responders in Terms of HbA1C ≤ 6.5% [at 4th month]

4. Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) [from baseline to 4 months]

5. Percentage Change in High-density Lipoprotein Cholesterol (HDL-C) [from baseline to 4 months]

6. Percentage Change in Triglycerides [from baseline to 4 months]

7. Change in High-sensitivity C-reactive Protein (Hs-CRP) [from baseline to 4 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• women of non-childbearing potential.

• Provision of informed consent prior to any study specific procedures

• Naïve T2DM patients with HbA1c ≥ 7.5% but ≤ 10% or T2DM Patients treated with one or two oral anti-hyperglycaemic agent(s) with HbA1c ≥ 7.5% but ≤ 9.5% at enrolment visit (Visit1)

Exclusion Criteria:

• Clinically relevant medical history or concurrent disease such as cardiovascular disease, renal disease, hepatic disease and haematological disease.

• The investigator(s) judged that the Subject should not participate in the study according to screening test or medical history.

• Participation in another clinical trial and/or intake of another investigational drug within the last 30 days prior to enrolment visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Osaka		Japan
2	Research Site	Suita		Japan
3	Research Site	Tokyo		Japan

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Maria Leonsson-Zachrisson, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01152385
• Other Study ID Numbers: D1020C00016
• First Posted: Jun 29, 2010
• Last Update Posted: Aug 27, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by AstraZeneca: Type 2 diabetes mellitus; Japanese; phase 2; AZD1656; efficacy; dose regimen; pharmacokinetics
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	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 Detail	Wash-out period for patients treated with anti-diabetes treatment at enrolment.

Arm/Group Title	High Dose	Middle Dose	Low Dose	Placebo
Arm/Group Description	200 mg (daily dose)	140 mg (daily dose)	80 mg (daily dose)	Placebo
Period Title: Overall Study
STARTED	55	58	56	55
COMPLETED	46	52	51	50
NOT COMPLETED	9	6	5	5

Baseline Characteristics

Arm/Group Title	High Dose	Middle Dose	Low Dose	Placebo	Total
Arm/Group Description	200 mg (daily dose)	140 mg (daily dose)	80 mg (daily dose)	Placebo	Total of all reporting groups
Overall Participants	55	58	56	55	224
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57 (9)	55 (9)	55 (10)	57 (9)	56 (9)
Sex: Female, Male (Count of Participants)
Female	7 12.7%	8 13.8%	8 14.3%	9 16.4%	32 14.3%
Male	48 87.3%	50 86.2%	48 85.7%	46 83.6%	192 85.7%

Outcome Measures

1. Primary Outcome

Title	Change in Haemoglobin A1c (HbA1c)
Time Frame	from baseline to 4 months

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High Dose	Arm 2 - Middle Dose	Arm 3 - Low Dose	Arm 4 - Placebo Dose
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	54	55
Mean (Standard Deviation) [Percentage]	0.0 (1.2)	-0.3 (1.3)	0.1 (1.2)	0.2 (0.7)

2. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG)
Time Frame	from baseline to 4 months

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High Dose	Arm 2 - Middle Dose	Arm 3 - Low Dose	Arm 4 - Placebo Dose
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	56	55
Mean (Standard Deviation) [mg/dL]	9 (42)	6 (45)	1 (36)	16 (28)

3. Secondary Outcome

Title	Number of Responders in Terms of HbA1C ≤ 7%
Time Frame	at 4th month

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	54	55
Number [Participants]	7 12.7%	16 27.6%	7 12.5%	1 1.8%

4. Secondary Outcome

Title	Number of Responders in Terms of HbA1C ≤ 6.5%
Time Frame	at 4th month

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	54	55
Number [Participants]	2 3.6%	8 13.8%	2 3.6%	0 0%

5. Secondary Outcome

Title	Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C)
Time Frame	from baseline to 4 months

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	56	55
Mean (Standard Deviation) [Percentage]	8.9 (19.9)	7.7 (18.8)	4.0 (15.6)	5.8 (18.4)

6. Secondary Outcome

Title	Percentage Change in High-density Lipoprotein Cholesterol (HDL-C)
Time Frame	from baseline to 4 months

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	56	55
Mean (Standard Deviation) [Percentage]	8.8 (18.0)	8.7 (12.9)	11.6 (12.7)	8.5 (12.5)

7. Secondary Outcome

Title	Percentage Change in Triglycerides
Time Frame	from baseline to 4 months

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	56	55
Mean (Standard Deviation) [Percentage]	10.8 (44.0)	25.0 (58.5)	6.7 (29.4)	18.1 (46.8)

8. Secondary Outcome

Title	Change in High-sensitivity C-reactive Protein (Hs-CRP)
Time Frame	from baseline to 4 months

Outcome Measure Data

Analysis Population Description

The analysis population was prior to rescue treatment (FAS)

Arm/Group Title	Arm 1 - High	Arm 2 - Middle	Arm 3 - Low	Arm 4 - Placebo
Arm/Group Description	AZD1656 titration 40 - 80 - 140 - 200 mg (daily dose)	AZD1656 titration 20 - 40 - 80 - 140 mg (daily dose)	AZD1656 titration 10 - 20 - 40 - 80 mg (daily dose)	Placebo
Measure Participants	55	58	54	55
Mean (Standard Deviation) [mg/dL]	0.058 (0.138)	0.021 (0.117)	0.033 (0.125)	-0.007 (0.115)

Adverse Events

Arm/Group Title	High Dose		Middle Dose		Low Dose		Placebo
Arm/Group Description	200 mg (daily dose)		140 mg (daily dose)		80 mg (daily dose)		Placebo
All Cause Mortality
	High Dose		Middle Dose		Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	High Dose		Middle Dose		Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/23 (0%)		0/28 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	High Dose		Middle Dose		Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/55 (29.1%)		19/58 (32.8%)		16/56 (28.6%)		16/55 (29.1%)
Eye disorders
Asthenopia	0/55 (0%)		0/58 (0%)		2/56 (3.6%)		0/55 (0%)
Gastrointestinal disorders
Diarrhoea	0/55 (0%)		2/58 (3.4%)		0/56 (0%)		0/55 (0%)
Infections and infestations
Nasopharyngitis	6/55 (10.9%)		9/58 (15.5%)		9/56 (16.1%)		11/55 (20%)
Bronchitis	2/55 (3.6%)		1/58 (1.7%)		0/56 (0%)		1/55 (1.8%)
Pharyngitis	2/55 (3.6%)		0/58 (0%)		1/56 (1.8%)		1/55 (1.8%)
Investigations
Aspartate Aminotransferase Increased	2/55 (3.6%)		2/58 (3.4%)		0/56 (0%)		0/55 (0%)
Alanine Aminotransferase Increased	1/55 (1.8%)		2/58 (3.4%)		0/56 (0%)		0/55 (0%)
Blood Triglycerides Increased	0/55 (0%)		2/58 (3.4%)		0/56 (0%)		0/55 (0%)
Electrocardiogram T Wave Inversion	0/55 (0%)		0/58 (0%)		2/56 (3.6%)		0/55 (0%)
Metabolism and nutrition disorders
Diabetes Mellitus	2/55 (3.6%)		2/58 (3.4%)		1/56 (1.8%)		1/55 (1.8%)
Musculoskeletal and connective tissue disorders
Back Pain	2/55 (3.6%)		1/58 (1.7%)		1/56 (1.8%)		1/55 (1.8%)
Nervous system disorders
Headache	2/55 (3.6%)		0/58 (0%)		1/56 (1.8%)		0/55 (0%)
Dizziness	2/55 (3.6%)		0/58 (0%)		0/56 (0%)		0/55 (0%)
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Inflammation	1/55 (1.8%)		2/58 (3.4%)		2/56 (3.6%)		0/55 (0%)
Skin and subcutaneous tissue disorders
Eczema Asteatotic	0/55 (0%)		0/58 (0%)		1/56 (1.8%)		2/55 (3.6%)

Limitations/Caveats

[Not Specified]

More Information

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.