Clinical trial NCT00286429: Efficacy and Safety Study of Alogliptin and Insulin in the Treatment of Type 2 Diabetes.
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 Insulin in Subjects With Type 2 Diabetes
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: 390
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 determine the efficacy and safety of alogliptin, once daily (QD), taken in combination with insulin for the treatment of Type 2 Diabetes.

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 alogliptin (SYR-322) for 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 insulin in subjects who are inadequately controlled on insulin alone (with or without metformin). 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 and currently treated with insulin alone (with or without metformin), and is inadequately controlled. Metformin dose must be stable for at least 8 weeks prior to Randomization.
* No treatment with antidiabetic agents other than insulin and metformin within the 8 weeks prior to Randomization.
* 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 greater than or equal to 1.5 ng per mL after a challenge test).
* Glycosylated hemoglobin concentration greater than or equal to 8.0% at Screening.
* Using a stable dose of insulin of at least 15 units but not more than 100 units per day for at least 8 weeks prior to Randomization. A dose of insulin that varies by up to 15% of the mean will be considered as stable.
* 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 to180 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 3 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 (confirmed by laboratory testing in females of childbearing potential) 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 own blood glucose concentrations with a home glucose monitor
* No major illness or debility that in the investigator's opinion prohibits the individual 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. (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 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 insulin and metformin is not allowed within the 8 weeks prior to Randomization and through the completion of the end-of treatment or early termination procedures. (Exception: if has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.)
  * 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 or early termination procedures. Inhaled corticosteroids are allowed.
  * 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 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: 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: Tustin
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Cocoa Beach
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: 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: Avon
country: United States
state: Indiana
city: Evansville
country: United States
state: Indiana
city: Lafayette
country: United States
state: Indiana
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: Winston Salem
country: United States
state: North Carolina
city: Cincinnati
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: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Simpsonville
country: United States
state: South Carolina
city: Cookeville
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: Chile
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: Poland
city: Multiple Cities
country: South Africa
Study officials:
affiliation: Takeda
name: VP Biological Sciences
role: STUDY_DIRECTOR
References:
citation: Rosenstock J, Rendell MS, Gross JL, Fleck PR, Wilson CA, Mekki Q. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab. 2009 Dec;11(12):1145-52. doi: 10.1111/j.1463-1326.2009.01124.x. Epub 2009 Sep 16.
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.