Clinical trial NCT00856284: Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Patients With Type 2 Diabetes Mellitus
Official title: A Multicenter, Randomized, Double-Blind, Active-Controlled Study to Evaluate the Durability of the Efficacy and Safety of Alogliptin Compared to Glipizide When Used in Combination With Metformin in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Mellitus
Drug Therapy
Hyperinsulinism
Hyperglycemia
Glucose Intolerance
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-03-05
Enrollment: 2639
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 safety and effectiveness of adding alogliptin, once daily (QD), compared to glipizide with metformin in diabetic patients.

Detailed description: For patients diagnosed with type 2 diabetes mellitus, metformin is the usual first-line therapy in addition to diet control and exercise. For those patients with inadequate glycemic control with metformin monotherapy or experiencing serious side effects of metformin, sulfonylurea is a popular choice as a second-line oral antidiabetic treatment.

Alogliptin is a dipeptidyl peptidase-4 inhibitor currently being developed by Takeda for use in patients with type 2 diabetes mellitus.

This study is designed to further explore the durability of efficacy and safety of alogliptin compared to glipizide in type 2 diabetes mellitus patients whose blood sugar level is inadequately controlled with metformin therapy.

The duration of this study will be approximately 2 years.

Eligibility criteria: Inclusion Criteria:

* Has a diagnosis of type 2 diabetes mellitus.
* Must meet one of the following:

  * Has been inadequately controlled on a stable daily dose of ≥1500 mg (or documented maximum tolerated dose) of metformin for at least 2 months prior to Screening.
  * Has been inadequately controlled (as defined by a glycosylated hemoglobin 7.5 - 10%, inclusive) on metformin \<1500 mg without documented maximum tolerated dose.
* No treatment with antidiabetic agents other than metformin within 2 months prior to Screening (for Schedule A)/Pre-Screening (for Schedule B).
* Has body mass index within 23 kg/m\^2 and 45 kg/m\^2 unless the patient is Asian or of Asian descent, for whom the allowable body mass index will be ≥ 20 kg/m\^2 and ≤ 35 kg/m\^2, inclusive.
* Has fasting C-peptide concentration at least 0.8 ng.
* If regularly using non-excluded medications, must be on a stable dose at least 4 weeks prior to Screening/Pre-screening.
* Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant, lactating or intends to donate ova from Screening throughout the duration of the study.
* Must be able and willing to monitor their blood glucose concentrations with a home monitor, and comply with protocol requirements including scheduled clinic appointments.

Exclusion Criteria:

* Systolic blood pressure greater than or equal to 150 mmHg and/or diastolic pressure greater than or equal to 90.
* Hemoglobin less than or equal to 12 g/dL for males and less than or equal to 10 g/dL for females at Screening Visit.
* Alanine aminotransferase greater than or equal to 2.5 times the upper limit of normal at Screening Visit.
* Serum creatinine greater than or equal to 1.5 mg/dL for males and 1.4 for females, or calculated creatinine clearance less than 60 L/min.
* Males intending to impregnate others or donate sperm before, during or within 1 month after participating in the study.
* A history of cancer other than squamous or basal cell carcinoma of the skin that has not been in full remission for at least 5 years.
* A history of laser treatment for diabetic retinopathy within 6 months of screening.
* Treated for diabetic gastric paresis, gastric banding, or gastric bypass.
* New York Heart Association Class III or IV heart failure.
* History of coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction, stroke or transient ischemic attack within 3 months prior to screening.
* Known history of human immunodeficiency virus, hepatitis B or C.
* Alcohol or substance abuse within 2 years prior to screening.
* Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  * Any investigational drug within 30 days
  * Any investigational diabetic drug within 3 months
  * Any antidiabetic drug in the dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 mimetics classes within 90 days prior to Screening other than metformin
  * Prior treatment with alogliptin.
  * Weight-loss drugs
  * Oral or systemically injected glucocorticoids
* A hypersensitivity allergy or anaphylactic reaction to any dipeptidyl peptidase-4 drug, metformin or glipizide.
* Has a documented history or concurrent signs of significant thyroid disease (eg, autoimmune thyroid diseases such as Graves disease and Hashimoto thyroiditis or active thyroid nodules).

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 104
timeFrame: Baseline and Week 104
Secondary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin at Other Time Points
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 26, 39, 65, 78, and 91.
measure: Change From Baseline in Fasting Plasma Glucose Over Time
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 26, 39, 52, 65, 78, 91, and 104.
measure: Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%
timeFrame: Weeks 26, 52, 78, and 104.
measure: Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%
timeFrame: Weeks 26, 52, 78, and 104.
measure: Change From Baseline in Body Weight Over Time
timeFrame: Baseline and Weeks 12, 26, 39, 52, 65, 78, 91, and 104.
Other outcomes:
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state: San Juan de Miraflores
city: Ica
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city: Gniewkowo
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city: Krakow
country: Poland
city: Radom
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country: Poland
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country: Romania
city: Arkhangelsk
country: Russian Federation
city: Irkutsk
country: Russian Federation
city: Moscow
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city: Samara
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Singapore
country: Singapore
city: Port Elizabeth
country: South Africa
state: Eastern Cape
city: Johannesburg
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: Kwazulu-Natal
city: Tongaat
country: South Africa
state: Kwazulu-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: Barcelona
country: Spain
state: Cataluña
city: Santiago de Compostela
country: Spain
state: Galicia
city: Alicante
country: Spain
city: Amphure Muang
country: Thailand
city: Bangkok
country: Thailand
city: Chiangmai
country: Thailand
city: Khon Kaen
country: Thailand
city: Dnepropertovsk
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Vinnytsa
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Zaporizhye
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Aintree-Liverpool
country: United Kingdom
city: Bath
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: Dundee
country: United Kingdom
city: London
country: United Kingdom
city: Stevenage
country: United Kingdom
city: Swansea
country: United Kingdom
Study officials:
affiliation: Takeda
name: Medical Director, Clinical Science
role: STUDY_DIRECTOR
References:
citation: Gordon J, McEwan P, Hurst M, Puelles J. The Cost-Effectiveness of Alogliptin Versus Sulfonylurea as Add-on Therapy to Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus. Diabetes Ther. 2016 Dec;7(4):825-845. doi: 10.1007/s13300-016-0206-7. Epub 2016 Oct 27.