Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00395512




Registration number
NCT00395512
Ethics application status
Date submitted
1/11/2006
Date registered
3/11/2006
Date last updated
27/03/2013

Titles & IDs
Public title
Efficacy of Alogliptin With Pioglitazone (Actos®) in Subjects With Type 2 Diabetes Mellitus
Scientific title
A Multicenter, Double-Blind Study to Determine the Efficacy and Safety of SYR-322 Plus Pioglitazone HCl (Actos®), SYR-322 Alone or Pioglitazone HCl Alone in Subjects With Type 2 Diabetes
Secondary ID [1] 0 0
2006-005492-17
Secondary ID [2] 0 0
01-06-TL-322OPI-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Alogliptin
Treatment: Drugs - Pioglitazone
Treatment: Drugs - Placebo

Experimental: Alogliptin 25 mg QD - Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.

Active comparator: Pioglitazone 30 mg QD - Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.

Experimental: Alogliptin 25 mg QD+ Pioglitazone 30 mg QD - Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.

Active comparator: Alogliptin 12.5 mg QD + Pioglitazone 30 mg QD - Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.


Treatment: Drugs: Alogliptin
Alogliptin tablets.

Treatment: Drugs: Pioglitazone
Pioglitazone tablets.

Treatment: Drugs: Placebo
Matching placebo tablets.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c)
Timepoint [1] 0 0
Baseline and Week 26
Secondary outcome [1] 0 0
Change From Baseline in HbA1c Over Time
Timepoint [1] 0 0
Baseline and Weeks 4, 8, 12, 16 and 20.
Secondary outcome [2] 0 0
Change From Baseline in Fasting Plasma Glucose Over Time
Timepoint [2] 0 0
Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Secondary outcome [3] 0 0
Percentage of Participants With Marked Hyperglycemia
Timepoint [3] 0 0
Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Secondary outcome [4] 0 0
Percentage of Participants Meeting Rescue Criteria
Timepoint [4] 0 0
Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [5] 0 0
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%
Timepoint [5] 0 0
Week 26
Secondary outcome [6] 0 0
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%
Timepoint [6] 0 0
Week 26
Secondary outcome [7] 0 0
Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5%
Timepoint [7] 0 0
Week 26
Secondary outcome [8] 0 0
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5%
Timepoint [8] 0 0
Baseline and Week 26
Secondary outcome [9] 0 0
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0%
Timepoint [9] 0 0
Baseline and Week 26
Secondary outcome [10] 0 0
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%.
Timepoint [10] 0 0
Baseline and Week 26
Secondary outcome [11] 0 0
Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0%
Timepoint [11] 0 0
Baseline and Week 26
Secondary outcome [12] 0 0
Change From Baseline in Fasting Proinsulin
Timepoint [12] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [13] 0 0
Change From Baseline in Insulin
Timepoint [13] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [14] 0 0
Change From Baseline in Proinsulin/Insulin Ratio
Timepoint [14] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [15] 0 0
Change From Baseline in C-peptide Levels
Timepoint [15] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [16] 0 0
Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance
Timepoint [16] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [17] 0 0
Change From Baseline in Homeostatic Model Assessment Beta Cell Function
Timepoint [17] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [18] 0 0
Change From Baseline in Body Weight
Timepoint [18] 0 0
Baseline and Weeks 8, 12, 20 and 26.
Secondary outcome [19] 0 0
Change From Baseline in Total Cholesterol Level
Timepoint [19] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [20] 0 0
Change From Baseline in Low-Density Lipoprotein Cholesterol
Timepoint [20] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [21] 0 0
Change From Baseline in High-Density Lipoprotein Cholesterol
Timepoint [21] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [22] 0 0
Change From Baseline in Triglyceride Levels
Timepoint [22] 0 0
Baseline and Weeks 4, 8, 12, 16, 20 and 26.
Secondary outcome [23] 0 0
Change From Baseline in Free Fatty Acids
Timepoint [23] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [24] 0 0
Change From Baseline in Plasminogen Activator Inhibitor-1
Timepoint [24] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [25] 0 0
Change From Baseline in High-sensitivity C-Reactive Protein
Timepoint [25] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [26] 0 0
Change From Baseline in Adiponectin
Timepoint [26] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [27] 0 0
Change From Baseline in Apolipoprotein A1
Timepoint [27] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [28] 0 0
Change From Baseline in Apolipoprotein A2
Timepoint [28] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [29] 0 0
Change From Baseline in Apolipoprotein B
Timepoint [29] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [30] 0 0
Change From Baseline in Apolipoprotein C-III
Timepoint [30] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [31] 0 0
Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides
Timepoint [31] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [32] 0 0
Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles
Timepoint [32] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [33] 0 0
Change From Baseline in VLDL / Chylomicron Triglycerides
Timepoint [33] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [34] 0 0
Change From Baseline in VLDL Particles
Timepoint [34] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [35] 0 0
Change From Baseline in Mean VLDL Particle Size
Timepoint [35] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [36] 0 0
Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles
Timepoint [36] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [37] 0 0
Change From Baseline in Low Density Lipoprotein (LDL) Particles
Timepoint [37] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [38] 0 0
Change From Baseline in Mean LDL Particle Size
Timepoint [38] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [39] 0 0
Change From Baseline in High Density Lipoprotein (HDL) Particles
Timepoint [39] 0 0
Baseline and Weeks 12 and 26.
Secondary outcome [40] 0 0
Change From Baseline in Mean HDL Particle Size
Timepoint [40] 0 0
Baseline and Weeks 12 and 26.

Eligibility
Key inclusion criteria
Inclusion Criteria

* Historical diagnosis of type 2 diabetes.
* Failed treatment with diet and exercise for at least 2 months prior to Screening.
* Is experiencing inadequate glycemic control as defined as glycosylated hemoglobin concentration between 7.5-11%, inclusive.
* Has received any antidiabetic therapy for less than 7 days within 3 months prior to Screening.
* Has a body mass index greater than or equal to 23 kg/m2 and less than or equal to45 kg/m2.
* Fasting C-peptide greater than or equal to 0.8 ng per mL.
* Regular use of other, non-excluded medications is allowed if participant is on a stable dose for at least 4 weeks prior to Screening.
* Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
* Must be willing and able to monitor their blood concentrations with a home glucose monitor.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure greater than or equal to 100 mmHg.
* Hemoglobin less than or equal to 12 g per dL for males and less than or equal to 10 g per dL for females.
* Alanine aminotransferase greater than or equal to 2.5times the upper limit of normal.
* Serum creatinine greater than 2.0 mg per dL.
* Thyroid stimulating hormone level greater than the upper limit of normal range.
* Major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
* Urine albumin to creatinine ratio of greater than 1000 ug per mg at Screening. If elevated, the subject may be rescreened within 1 week.
* History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening
* History of laser treatment for proliferative diabetic retinopathy within 6 months prior to Screening.
* History of gastroparesis.
* Has New York Heart Association Class I to IV heart failure regardless of therapy.
* History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.
* History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.
* History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
* History of a psychiatric disorder that will affect participant's ability to participate in the study.
* History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
* Any alteration in angiotensin-II receptor inhibitors within 2 months prior to Randomization, if applicable.
* History of alcohol (defined as regular or daily consumption of more than 4 alcoholic drinks per day) or substance abuse (defined as illicit drug use) within 2 years prior to Screening.
* Received any investigational drug within 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within 3 months prior to Screening.
* Previously participated in an investigational study of SYR-322.
* Glycosylated hemoglobin concentration between 7.5-11%, inclusive, and a fasting plasma glucose less than 310 mg per dL.
* At least 75% compliant with the single-blind placebo regimen during the run-in/stabilization period.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2008
Sample size
Target
Accrual to date
Final
655
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Kingswood
Recruitment hospital [2] 0 0
- Fitzroy
Recruitment hospital [3] 0 0
- Frankston
Recruitment postcode(s) [1] 0 0
- Kingswood
Recruitment postcode(s) [2] 0 0
- Fitzroy
Recruitment postcode(s) [3] 0 0
- Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Mississippi
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Montana
Country [16] 0 0
United States of America
State/province [16] 0 0
Nevada
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
North Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Oregon
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
South Carolina
Country [25] 0 0
United States of America
State/province [25] 0 0
Tennessee
Country [26] 0 0
United States of America
State/province [26] 0 0
Texas
Country [27] 0 0
United States of America
State/province [27] 0 0
Utah
Country [28] 0 0
United States of America
State/province [28] 0 0
Virginia
Country [29] 0 0
United States of America
State/province [29] 0 0
West Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Wisconsin
Country [31] 0 0
Argentina
State/province [31] 0 0
Buenos Aires
Country [32] 0 0
Argentina
State/province [32] 0 0
Córdoba
Country [33] 0 0
Brazil
State/province [33] 0 0
CE
Country [34] 0 0
Brazil
State/province [34] 0 0
GO
Country [35] 0 0
Brazil
State/province [35] 0 0
PA
Country [36] 0 0
Brazil
State/province [36] 0 0
PR
Country [37] 0 0
Brazil
State/province [37] 0 0
RP
Country [38] 0 0
Brazil
State/province [38] 0 0
SP
Country [39] 0 0
Bulgaria
State/province [39] 0 0
Pleven
Country [40] 0 0
Chile
State/province [40] 0 0
Santiago
Country [41] 0 0
Croatia
State/province [41] 0 0
Slavonski Brod
Country [42] 0 0
Estonia
State/province [42] 0 0
Pärnu
Country [43] 0 0
Guatemala
State/province [43] 0 0
Guatemala
Country [44] 0 0
Hungary
State/province [44] 0 0
Budapest
Country [45] 0 0
Hungary
State/province [45] 0 0
Eger
Country [46] 0 0
Hungary
State/province [46] 0 0
Gyula
Country [47] 0 0
Hungary
State/province [47] 0 0
Mako
Country [48] 0 0
Hungary
State/province [48] 0 0
Nyiregyhaza
Country [49] 0 0
Hungary
State/province [49] 0 0
Pecs
Country [50] 0 0
India
State/province [50] 0 0
Andhra Pradesh
Country [51] 0 0
India
State/province [51] 0 0
Karnataka
Country [52] 0 0
India
State/province [52] 0 0
Maharashtra
Country [53] 0 0
India
State/province [53] 0 0
Tamil Nadu
Country [54] 0 0
Israel
State/province [54] 0 0
Hadera
Country [55] 0 0
Israel
State/province [55] 0 0
Haifa
Country [56] 0 0
Israel
State/province [56] 0 0
Holon
Country [57] 0 0
Israel
State/province [57] 0 0
Jaffa Tel Aviv
Country [58] 0 0
Israel
State/province [58] 0 0
Jerusalem
Country [59] 0 0
Israel
State/province [59] 0 0
Nahariya
Country [60] 0 0
Latvia
State/province [60] 0 0
Riga
Country [61] 0 0
Lithuania
State/province [61] 0 0
Kaunas
Country [62] 0 0
Lithuania
State/province [62] 0 0
Kedainiai
Country [63] 0 0
Mexico
State/province [63] 0 0
Aguascalientes
Country [64] 0 0
Mexico
State/province [64] 0 0
Mexico City
Country [65] 0 0
Mexico
State/province [65] 0 0
Monterrey
Country [66] 0 0
New Zealand
State/province [66] 0 0
Christchurch
Country [67] 0 0
New Zealand
State/province [67] 0 0
Hamilton
Country [68] 0 0
Poland
State/province [68] 0 0
Bialystok
Country [69] 0 0
Poland
State/province [69] 0 0
Bytom
Country [70] 0 0
Poland
State/province [70] 0 0
Gdansk
Country [71] 0 0
Poland
State/province [71] 0 0
Gniewkowo
Country [72] 0 0
Poland
State/province [72] 0 0
Kamieniec Zabkowicki
Country [73] 0 0
Poland
State/province [73] 0 0
Krakow
Country [74] 0 0
Poland
State/province [74] 0 0
Leczyca
Country [75] 0 0
Romania
State/province [75] 0 0
Brasov
Country [76] 0 0
Romania
State/province [76] 0 0
Bucharest
Country [77] 0 0
Romania
State/province [77] 0 0
Galati
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Ekaterinburg
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Kazan
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Moscow
Country [81] 0 0
Serbia
State/province [81] 0 0
Belgrade
Country [82] 0 0
Serbia
State/province [82] 0 0
Kragujevac
Country [83] 0 0
Serbia
State/province [83] 0 0
Nis
Country [84] 0 0
Slovakia
State/province [84] 0 0
Nitra
Country [85] 0 0
Slovakia
State/province [85] 0 0
Banska Bysterica
Country [86] 0 0
Slovakia
State/province [86] 0 0
Lucenec
Country [87] 0 0
Slovakia
State/province [87] 0 0
Riverside
Country [88] 0 0
Slovakia
State/province [88] 0 0
Sahy
Country [89] 0 0
South Africa
State/province [89] 0 0
Eastern Cape
Country [90] 0 0
South Africa
State/province [90] 0 0
Gauteng
Country [91] 0 0
South Africa
State/province [91] 0 0
Kwa-Zulu Natal
Country [92] 0 0
South Africa
State/province [92] 0 0
Pretoria
Country [93] 0 0
South Africa
State/province [93] 0 0
Western Province
Country [94] 0 0
Ukraine
State/province [94] 0 0
Dnipropetrovsk
Country [95] 0 0
Ukraine
State/province [95] 0 0
Kharkiv
Country [96] 0 0
Ukraine
State/province [96] 0 0
Lviv
Country [97] 0 0
Ukraine
State/province [97] 0 0
Odesa

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the combination of alogliptin, once daily (QD), and pioglitazone in patients with type 2 diabetes mellitus who are inadequately controlled with diet and exercise alone.
Trial website
https://clinicaltrials.gov/study/NCT00395512
Trial related presentations / publications
Rosenstock J, Inzucchi SE, Seufert J, Fleck PR, Wilson CA, Mekki Q. Initial combination therapy with alogliptin and pioglitazone in drug-naive patients with type 2 diabetes. Diabetes Care. 2010 Nov;33(11):2406-8. doi: 10.2337/dc10-0159. Epub 2010 Aug 19.
Public notes

Contacts
Principal investigator
Name 0 0
VP, Biological Sciences
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00395512