Clinical trial NCT00286494: Study of Alogliptin Combined With Pioglitazone in Subjects With Type 2 Diabetes Mellitus
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of SYR110322 (SYR-322) When Used in Combination With Pioglitazone in Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus
Keywords: Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus
Lipoatrophic
Dyslipidemia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2006-02-03
Enrollment: 493
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of alogliptin, once daily (QD), combined with pioglitazone in adults with type 2 diabetes mellitus

Detailed description: There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% are type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected.

Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes.

The aim of the current study is to evaluate the efficacy of alogliptin in combination with pioglitazone in subjects who are inadequately controlled on a thiazolidinedione (pioglitazone or rosiglitazone) alone or in combination with metformin or a sulfonylurea. Individuals who participate in this study will be required to commit to a screening visit and up to 14 additional visits at the study center. Study participation is anticipated to be about 34 weeks (or 8.5 months).

Eligibility criteria: Inclusion Criteria

* Diagnosis of type 2 diabetes mellitus currently treated with a thiazolidinedione either alone or in combination with metformin or a sulfonylurea but who are experiencing inadequate glycemic control. The subject should have received the thiazolidinedione therapy (rosiglitazone or pioglitazone) either alone or in combination with metformin or a sulfonylurea for at least the 3 months prior to Screening and must have been on a stable dose for all their antidiabetic treatments for at least the month prior to Screening.
* No treatment with antidiabetic agents other than a thiazolidinedione alone or in combination with either metformin or a sulfonylurea within the 3 months prior to Screening. (Exception: if a subject has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.)
* Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2
* Fasting C-peptide concentration greater than or equal to 0.8 ng per mL. (If this screening criterion is not met, the subject still qualifies if C-peptide is greater than or equal to 1.5 ng per mL after a challenge test.)
* Glycosylated hemoglobin concentration between 7.0% and 10.0%, inclusive.
* If regular use of other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
* Systolic blood pressure less than or equal to 180 mm Hg and diastolic pressure less than or equal to 110 mm Hg.
* Hemoglobin greater than or equal to 12 g per dL for males and greater than or equal to10 g per dL for females.
* Alanine aminotransferase less than or equal to 2.5 times the upper limit of normal.
* Serum creatinine less than or equal to 2.0 mg per dL.
* Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject is clinically euthyroid.
* Neither pregnant nor lactating.
* Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study.
* Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.
* No major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
* Able and willing to provide written informed consent.

Exclusion Criteria

* Urine albumin to creatinine ratio of greater than 1000 μg 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. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.)
* History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
* History of treated diabetic gastric paresis.
* New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study.
* History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 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 the subject's ability to participate in the study.
* History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
* History of alcohol or substance abuse within the 2 years prior to Screening.
* Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening.
* Prior treatment in an investigational study of alogliptin.
* Excluded Medications:

  * Treatment with antidiabetic agents other than a thiazolidinedione alone or in combination with either metformin or a sulfonylurea is not allowed within the 3 months prior to Screening and through the completion of the end-of-treatment/early termination procedures.
  * Treatment with weight-loss drugs, any investigational antidiabetics, or oral or systemically injected glucocorticoids is not allowed from 3 months prior to randomization through the completion of the end-of-treatment/early termination procedures. Inhaled corticosteroids are allowed.

Subjects must not take any medications, including over-the-counter products, without first consulting with the investigator.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26.
timeFrame: Baseline and Week 26.
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in Glycosylated Hemoglobin (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Fasting Plasma Glucose (Week 1).
timeFrame: Baseline and Week 1.
measure: Change From Baseline in Fasting Plasma Glucose (Week 2).
timeFrame: Baseline and Week 2.
measure: Change From Baseline in Fasting Plasma Glucose (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Fasting Plasma Glucose (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Fasting Plasma Glucose (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Fasting Plasma Glucose (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in Fasting Plasma Glucose (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Fasting Plasma Glucose (Week 26).
timeFrame: Baseline and Week 26.
measure: Number of Participants With Marked Hyperglycemia (Fasting Plasma Glucose ≥ 200 mg Per dL).
timeFrame: 26 Weeks.
measure: Number of Participants Requiring Rescue.
timeFrame: 26 Weeks.
measure: Change From Baseline in Fasting Proinsulin (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Fasting Proinsulin (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Fasting Proinsulin (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Fasting Proinsulin (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in Fasting Proinsulin (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Fasting Proinsulin (Week 26).
timeFrame: Baseline and Week 26.
measure: Change From Baseline in Insulin (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Insulin (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Insulin (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Insulin (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in Insulin (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Insulin (Week 26).
timeFrame: Baseline and Week 26.
measure: Change From Baseline in Proinsulin/Insulin Ratio (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in Proinsulin/Insulin Ratio (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Proinsulin/Insulin Ratio (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Proinsulin/Insulin Ratio (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in Proinsulin/Insulin Ratio (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Proinsulin/Insulin Ratio (Week 26).
timeFrame: Baseline and Week 26.
measure: Change From Baseline in C-peptide (Week 4).
timeFrame: Baseline and Week 4.
measure: Change From Baseline in C-peptide (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in C-peptide (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in C-peptide (Week 16).
timeFrame: Baseline and Week 16.
measure: Change From Baseline in C-peptide (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in C-peptide (Week 26).
timeFrame: Baseline and Week 26.
measure: Number of Participants With Glycosylated Hemoglobin ≤ 6.5%.
timeFrame: Baseline and Week 26.
measure: Number of Participants With Glycosylated Hemoglobin ≤ 7.0%.
timeFrame: Baseline and Week 26.
measure: Number of Participants With Glycosylated Hemoglobin ≤ 7.5%.
timeFrame: Baseline and Week 26.
measure: Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 0.5%.
timeFrame: Baseline and Week 26.
measure: Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.0%.
timeFrame: Baseline and Week 26.
measure: Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 1.5%.
timeFrame: Baseline and Week 26.
measure: Number of Participants With Glycosylated Hemoglobin Decrease From Baseline ≥ 2.0%.
timeFrame: Baseline and Week 26.
measure: Change From Baseline in Body Weight (Week 8).
timeFrame: Baseline and Week 8.
measure: Change From Baseline in Body Weight (Week 12).
timeFrame: Baseline and Week 12.
measure: Change From Baseline in Body Weight (Week 20).
timeFrame: Baseline and Week 20.
measure: Change From Baseline in Body Weight (Week 26).
timeFrame: Baseline and Week 26.
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Anaheim
country: United States
state: California
city: Artesia
country: United States
state: California
city: Fresno
country: United States
state: California
city: Mission Viejo
country: United States
state: California
city: Northridge
country: United States
state: California
city: Orange
country: United States
state: California
city: San Diego
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Colorado Springs
country: United States
state: Colorado
city: Denver
country: United States
state: Colorado
city: Norwalk
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Clearwater
country: United States
state: Florida
city: Cocoa Beach
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Longwood
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Ocoee
country: United States
state: Florida
city: St. Cloud
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Lawrenceville
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Idaho Falls
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Avon
country: United States
state: Indiana
city: Elkhart
country: United States
state: Indiana
city: Evansville
country: United States
state: Indiana
city: Lafayette
country: United States
state: Indiana
city: Erlanger
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Sudbury
country: United States
state: Massachusetts
city: Chesterfield
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Berlin
country: United States
state: New Jersey
city: Burlington
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: Morehead City
country: United States
state: North Carolina
city: Pinehurst
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Dayton
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Medford
country: United States
state: Oregon
city: Lansdale
country: United States
state: Pennsylvania
city: West Grove
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Simpsonville
country: United States
state: South Carolina
city: Bristol
country: United States
state: Tennessee
city: Cookeville
country: United States
state: Tennessee
city: Milan
country: United States
state: Tennessee
city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Texarkana
country: United States
state: Texas
city: Burlington
country: United States
state: Vermont
city: Multiple Cities
country: Argentina
city: Multiple Cities
country: Australia
city: Multiple Cities
country: Brazil
city: Multiple Cities
country: Czech Republic
city: Multiple Cities
country: Germany
city: Multiple Cities
country: Guatemala
city: Multiple Cities
country: Hungary
city: Multiple Cities
country: India
city: Multiple Cities
country: Mexico
city: Multiple Cities
country: Netherlands
city: Multiple Cities
country: New Zealand
city: Multiple Cities
country: Peru
city: Multiple Cities
country: South Africa
Study officials:
affiliation: Takeda
name: VP Biological Sciences
role: STUDY_DIRECTOR
References:
citation: Pratley RE, Reusch JE, Fleck PR, Wilson CA, Mekki Q; Alogliptin Study 009 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin. 2009 Oct;25(10):2361-71. doi: 10.1185/03007990903156111.
citation: Pratley RE, McCall T, Fleck PR, Wilson CA, Mekki Q. Alogliptin use in elderly people: a pooled analysis from phase 2 and 3 studies. J Am Geriatr Soc. 2009 Nov;57(11):2011-9. doi: 10.1111/j.1532-5415.2009.02484.x. Epub 2009 Sep 30.