Efficacy of Alogliptin and With Pioglitazone in Patients With Type 2 Diabetes.

Tracking Information
First Submitted Date ICMJE	April 4, 2008
First Posted Date ICMJE	April 10, 2008
Results First Submitted Date	February 17, 2013
Results First Posted Date	May 27, 2013
Last Update Posted Date	May 27, 2013
Study Start Date ICMJE	July 2007
Actual Primary Completion Date	December 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 23, 2013)	Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 16. [ Time Frame: Baseline and Week 16. ]; The change in postprandial (after eating a meal) incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC (0-8h)) postdose at week 16 relative to baseline.
Original Primary Outcome Measures ICMJE; (submitted: April 9, 2008)	To evaluate the change from Baseline in postprandial incremental area under the curve for triglycerides at Week 16. [ Time Frame: 16 weeks ]
Change History	Complete list of historical versions of study NCT00655863 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 23, 2013)	Change From Baseline in Postprandial Incremental Area Under the Curve for Total Triglycerides at Week 4. [ Time Frame: Baseline and Week 4. ]The change in postprandial incremental area under the plasma concentration-time curve from 0 to 8 hours (AUC(0-8h)) postdose at week 4 relative to baseline.; Change From Baseline in Postprandial Incremental Area Under the Curve Changes for Lipid Parameters. [ Time Frame: Baseline, Week 4 and Week 16. ]The change in postprandial incremental area under the plasma concentration-time curve for very-low-density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL2 cholesterol, VLDL2 triglycerides, chylomicron cholesterol, chylomicron triglycerides, intermediate-density lipoprotein (IDL) cholesterol, and IDL triglycerides from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.; Change From Baseline in Postprandial Incremental Area Under the Curve for Lipoprotein Parameters. [ Time Frame: Baseline, Week 4 and Week 16. ]Postprandial incremental area under the curve changes for very-low-density lipoprotein (VLDL) Apo B-48, VLDL Apo B 100, VLDL2 Apo B-48, VLDL2 Apo B 100, chylomicron Apo B-48, chylomicron Apo B 100, and intermediate density lipoprotein (IDL) Apo B-48, IDL Apo B 100, and triglyceride-rich remnant (TRR) lipoproteins from 0 to 8 hours postdose at week 4 and week 16 relative to baseline.; Postprandial Changes Over Time From Baseline for Glucagon-like Peptide-1 (GLP-1) [ Time Frame: Baseline, Week 4 and Week 16. ]Postprandial changes over time at each week indicated relative to baseline.; Postprandial Changes Over Time From Baseline for Glucose [ Time Frame: Baseline, Week 4 and Week 16. ]Postprandial changes over time at each week indicated relative to baseline.; Postprandial Changes Over Time From Baseline for Insulin [ Time Frame: Baseline, Week 4 and Week 16. ]Postprandial changes over time at each week indicated relative to baseline.; Postprandial Changes Over Time From Baseline for Glucagon [ Time Frame: Baseline, Week 4 and Week 16. ]Postprandial changes over time at each week indicated relative to baseline.; Change From Baseline in Glycosylated Hemoglobin [ Time Frame: Baseline, Week 8 and Week 16. ]The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated relative to baseline.; Change From Baseline in Fasting Plasma Glucose [ Time Frame: Baseline, Week 4, Week 8 and Week 16. ]The change in fasting plasma glucose collected at each week indicated relative to baseline.; Change From Baseline in Postprandial C-Peptide [ Time Frame: Baseline, Week 4 and Week 16. ]The change in postprandial C-peptide collected at each week indicated relative to baseline.; Change From Baseline in Postprandial Proinsulin [ Time Frame: Baseline, Week 4 and Week 16. ]The change in postprandial proinsulin collected at each week indicated relative to baseline.; Change From Baseline in High-sensitive C-reactive Protein (Hs-CRP) [ Time Frame: Baseline, Week 4 and Week 16. ]The change in hs-CRP collected at each week indicated relative to baseline.; Change From Baseline in Adiponectin [ Time Frame: Baseline, Week 4 and Week 16. ]The change in adiponectin collected at each week indicated relative to baseline.; Change From Baseline in Anti-Vascular Cell Adhesion Molecule (VCAM) [ Time Frame: Baseline, Week 4 and Week 16. ]The change in VCAM collected at each week indicated relative to baseline.; Change From Baseline in Anti-Intercellular Adhesion Molecule (ICAM) [ Time Frame: Baseline, Week 4 and Week 16. ]The change in ICAM collected at each week indicated relative to baseline.; Change From Baseline in e-Selectin [ Time Frame: Baseline, Week 4 and Week 16. ]The change in e-Selectin collected at each week indicated relative to baseline.; Change From Baseline in Endothelial Function Through Pulse Wave Tonometry [ Time Frame: Baseline and Week 16. ]Pulse wave tonometry performed before the meal and 2 hours postmeal using one recording consisting of 15 to 20 sequentially recorded radial artery waveforms collected at each assessment.
Original Secondary Outcome Measures ICMJE; (submitted: April 9, 2008)	Efficacy: Postprandial incremental AUC changes for triglycerides at Week 4. [ Time Frame: 16 weeks ]; Postprandial incremental AUC changes for lipid parameters. [ Time Frame: 16 weeks ]; Postprandial incremental AUC changes for lipoprotein parameters. [ Time Frame: 16 weeks ]; Postprandial changes over time [ Time Frame: 16 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy of Alogliptin and With Pioglitazone in Patients With Type 2 Diabetes.
Official Title ICMJE	Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing SYR-322 Alone and Combination SYR-322 With Pioglitazone Versus Placebo on Postprandial Lipids in Subjects With Type 2 Diabetes
Brief Summary	The purpose of this study is to compare the efficacy of Alogliptin, once daily (QD), taken by itself and with pioglitazone on postprandial lipid measures in type 2 diabetes.
Detailed Description	SYR-322 (alogliptin) is a selective, orally available inhibitor of dipeptidyl peptidase IV being developed as a treatment for type 2 diabetes mellitus. Dipeptidyl peptidase IV is the primary enzyme involved in the in vivo degradation of at least 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Pioglitazone HCl (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan). Pioglitazone HCl depends on the presence of insulin for its mechanism of action. This study will assess the effects of alogliptin and alogliptin coadministered with pioglitazone HCl on postprandial lipid and lipoprotein metabolism in participants with type 2 diabetes. Individuals who participate in this study will be required to commit to a screening visit and up to 6 additional visits at the study center. Study participation is anticipated to be about 20 weeks (or approximately 5 months). Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations and electrocardiograms. At 3 of the visits a meal will be served that must be eaten within 10 minutes.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Diabetes Mellitus
Intervention ICMJE	Drug: Alogliptin and Pioglitazone Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 16 weeks. Other Names: alogliptin SYR110322 Actos AD-4833 SYR-322; Drug: Alogliptin Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. Other Names: SYR110322 SYR-322; Drug: Placebo Alogliptin placebo-matching tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 16 weeks. Other Names: Actos AD-4833 SYR-322
Study Arms	Placebo Comparator: Placebo QD Intervention: Drug: Placebo; Experimental: Alogliptin 25 mg QD Intervention: Drug: Alogliptin; Experimental: Alogliptin 25 mg QD + Pioglitazone 30 mg QD Intervention: Drug: Alogliptin and Pioglitazone
Publications *	Eliasson B, Möller-Goede D, Eeg-Olofsson K, Wilson C, Cederholm J, Fleck P, Diamant M, Taskinen MR, Smith U. Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study. Diabetologia. 2012 Apr;55(4):915-25. doi: 10.1007/s00125-011-2447-3. Epub 2012 Jan 12.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 8, 2010)	71
Original Estimated Enrollment ICMJE; (submitted: April 9, 2008)	75
Actual Study Completion Date	December 2009
Actual Primary Completion Date	December 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria; Diagnosis of type 2 diabetes; 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.; Either failed treatment with diet and exercise for 3 months prior to Screening or has been receiving a stable dose of metformin, sulfonylurea, nateglinide, or repaglinide for more than 3 months prior to Screening.; Inadequate glycemic control as defined by glycosylated hemoglobin concentration between 6.5 and 9.0%, inclusive.; Fasting plasma glucose less than 13.3 mmol per L.; Fasting serum triglyceride level of 1.7 to 5.0 mmol per L, inclusive.; Has not been receiving any lipid-lowering therapy within 3 months prior to Screening or on a stable statin and/or ezetimibe therapy (same drug and dose) for at least 3 months.; Body mass index greater than 23 kg/m2 and less than 45 kg/m2.; If has regular use of other, non-excluded medications, must be on a stable dose for at least 4 weeks prior to Screening. Use of as needed prescription medications and over-the-counter medications is allowed at the discretion of the investigator.; Is to be Apolipoprotein E 3/3 or Apolipoprotein E 3/4 phenotype positive prior to baseline. Exclusion Criteria; History of type 1 diabetes.; History of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within the past 2 years.; Diastolic blood pressure greater than 100 mm Hg or a systolic blood pressure of greater than 160 mm Hg.; History of cancer, other than basal cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study medication.; Hemoglobin less than 120 g per L for males and less than100 g per L for females.; Alanine transaminase level greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.; Serum creatinine level greater than 133 μmol per L.; Fasting total cholesterol greater than 6.5 mmol per L.; New York Heart Association heart failure of any Class (I-IV) regardless of therapy.; History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within 6 months prior to Screening.; History of acute metabolic diabetic complications.; History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.; History of infection with human immunodeficiency virus.; History of diabetic gastro paresis.; History of gastric bypass surgery.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 70 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Netherlands, Sweden
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00655863
Other Study ID Numbers ICMJE	SYR-322_301; 2007-000486-38 ( EudraCT Number ); U1111-1113-2081 ( Registry Identifier: WHO ); NL22649.029.08 ( Registry Identifier: CCMO )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Takeda
Study Sponsor ICMJE	Takeda
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Medical Director Takeda
PRS Account	Takeda
Verification Date	May 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP