Clinical trial NCT00707993: Efficacy and Safety of Alogliptin Compared to Glipizide in Elderly Diabetics
Official title: A Multicenter, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Alogliptin Compared to Glipizide in Elderly 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: 2008-07-02
Enrollment: 441
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: 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), compared to glipizide in elderly diabetic patients who have not received treatment or are on a single oral medication.

Detailed description: Type 2 diabetes is among the most common chronic condition in adults 65 years of age or older. A recent National Health and Nutrition Examination Survey reported that more than 20% of adults aged 65 years or older have diabetes. These individuals are often under-treated with respect to glucose-lowering medications, and their care is complicated by the extent of their clinical and functional status. Age-related changes in physiology, diabetes-associated illnesses and other illnesses (such as renal, cardiac, and hepatic insufficiency), as well as use of multiple medications make standard oral anti-hyperglycemic therapy and insulin use problematic. In addition, hypoglycemia is more common and severe in older rather than younger patients taking oral antidiabetic drugs which can precipitate serious events such as falls and hip fractures. While avoidance of hypoglycemia is paramount in elderly diabetic patients, many commonly used medications are associated with a substantial risk for hypoglycemia. New classes of drug which avoid such complications in the elderly population are of increasing interest as this population continues to expand.

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.

This study will compare the effectiveness and safety of alogliptin with that of glipizide (a commonly used diabetes medication) in adults who are 65 to 90 years of age with Type 2 diabetes. Individuals who participate in this study will either have failed diet and exercise therapy alone during the 2 months before Screening, or will have been receiving a single oral antidiabetic medication without obtaining good blood glucose (sugar) control.

Each participant will be required to commit to screening visits. Study participation is anticipated to be up to 59 weeks.

Eligibility criteria: Inclusion Criteria:

* Has a diagnosis of type 2 diabetes mellitus with either:

  * Failed diet and exercise therapy alone as demonstrated by inadequate glycemic control while receiving no antidiabetic treatment within the two months prior to Screening, or
  * Failed treatment with oral monotherapy alone (may include treatment with two or more antidiabetic agents if for less than 7 days) as demonstrated by inadequate glycemic control within the two months prior to Screening.
* Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2.
* If regularly using other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening.
* Females of childbearing potential who are sexually active must agree to use a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of 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 participant from completing the study.

Exclusion Criteria:

* Systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic pressure greater than or equal to 100 mm Hg.
* Hemoglobin less than or equal to 12 g/dL for males or less than or equal to 10 g/dL for females.
* Alanine aminotransferase greater than or equal to 3 times the upper limit of normal.
* Calculated creatinine clearance less than or equal to 50 mL/min.
* Thyroid-stimulating hormone level outside of the normal range.
* 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 the 6 months prior to Screening.
* History of treated diabetic gastroparesis, gastric banding, or gastric bypass surgery.
* New York Heart Association Class III or IV heart failure regardless of therapy.
* 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 Human Immunodeficiency Virus.
* History of a psychiatric disorder that will affect the 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.
* History of alcohol or substance abuse within the 2 years prior to Screening.
* History of treatment with any weight-loss drugs or oral or systemically injected glucocorticoids within the 3 months prior to Screening.
* Receipt of any investigational drug within the 30 days prior to Screening.
* Prior treatment in an investigational study of alogliptin.
* Clinically significant medical abnormality or disease or clinically significant abnormal findings at Screening (other than type 2 diabetes) that, in the opinion of the investigator, should exclude the participant from the study.
* Has donated more than 400 mL of blood within the 90 days preceding their participation in the study.
* Has hypersensitivity or has had an anaphylactic reaction(s) to any DPP-4 inhibitor drug.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin at Week 52.
timeFrame: Baseline and Week 52.
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34 and Week 42.
measure: Incidence of Hypoglycemia
timeFrame: On occurrence (up to 52 weeks).
measure: Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL).
timeFrame: On Occurrence (up to 52 weeks).
measure: Incidence of Hyperglycemic Rescue
timeFrame: On Occurrence (up to 52 weeks).
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34, Week 42 and Week 52.
measure: Change From Baseline in 2-hour Postprandial Glucose
timeFrame: Baseline and Week 52.
measure: Change From Baseline in Fasting Proinsulin
timeFrame: Baseline, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in Insulin
timeFrame: Baseline, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in Proinsulin/Insulin Ratio
timeFrame: Baseline, Week 12, Week 26, Week 42 and Week 52.
measure: Homeostasis Model Assessment of Beta Cell Function
timeFrame: Baseline, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in Serum Lipids (Total Cholesterol)
timeFrame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol)
timeFrame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol)
timeFrame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in Serum Lipids (Triglycerides)
timeFrame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
measure: Change From Baseline in High Sensitivity C-reactive Protein
timeFrame: Baseline, Week 12, Week 26, Week 42 and Week 52.
measure: Incidence of Subjects Achieving Glycosylated Hemoglobin <=7%
timeFrame: Baseline and Week 52.
measure: Incidence of Glycosylated Hemoglobin Decrease From Baseline.
timeFrame: Baseline and Week 52.
Other outcomes:
Locations:
city: Alexander City
country: United States
state: Alabama
city: Foothill Ranch
country: United States
state: California
city: Huntington Park
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Redlands
country: United States
state: California
city: Prospect
country: United States
state: Connecticut
city: Bradenton
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Ormond Beach
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Roswell
country: United States
state: Georgia
city: Aurora
country: United States
state: Illinois
city: LaPorte
country: United States
state: Indiana
city: South Bend
country: United States
state: Indiana
city: Salisbury
country: United States
state: Maryland
city: Clarkston
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: Hamilton
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Beachwood
country: United States
state: Ohio
city: Westlake
country: United States
state: Ohio
city: Zanesville
country: United States
state: Ohio
city: Bensalem
country: United States
state: Pennsylvania
city: Aiken
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Greer
country: United States
state: South Carolina
city: Taylors
country: United States
state: South Carolina
city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Pasadena
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Tomball
country: United States
state: Texas
city: Ogden
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Budapest
country: Hungary
city: Miskoic
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Karnal
country: India
state: Haryana
city: Bangalore
country: India
state: Karnataka
city: Belgaum
country: India
state: Karnataka
city: Mumbai
country: India
state: Maharashrta
city: Ashkelon
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Nahariya
country: Israel
city: Rishon Le-Zion
country: Israel
city: Zefat
country: Israel
city: Saltillo
country: Mexico
state: Coahuila
city: Pachuca
country: Mexico
state: Hidalgo
city: Morelia
country: Mexico
state: Michoacan
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Aguascalientes
country: Mexico
city: Durango
country: Mexico
city: Guadalajara
country: Mexico
city: Mexico DF
country: Mexico
city: Nezahualcoyotl
country: Mexico
city: Arequipa
country: Peru
city: Lima
country: Peru
city: Piura
country: Peru
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Warszawa
country: Poland
city: Baia Mare
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Galati
country: Romania
city: Satu Mare
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Irkutsk
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Cape Town
country: South Africa
city: Centurion
country: South Africa
city: Durban
country: South Africa
city: Johannesburg
country: South Africa
city: Port Elizabeth
country: South Africa
city: Pretoria
country: South Africa
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
Study officials:
affiliation: Takeda
name: VP Biological Sciences
role: STUDY_DIRECTOR
References: