Clinical trial NCT00306384: Long-term Safety of Alogliptin in Patients With Type 2 Diabetes Mellitus
Official title: A Long-Term, Open-Label Extension Study to Investigate the Long-Term Safety of SYR110322 (SYR-322) 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: 2006-03-23
Enrollment: 3323
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 long-term safety of alogliptin, once daily (QD), following participation in 1 of 7 controlled studies in patients with type 2 diabetes mellitus.

Detailed description: SYR-322 (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, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes mellitus by prolonging the beneficial effects of glucagon-like peptide-1.

The rising incidence of type 2 diabetes mellitus and the limitations of the currently available treatments suggest the need for new therapies for glycemic control. Studies have been undertaken in humans that evaluated the effects of directly augmenting glucagon-like peptide-1 and glucose-dependent insulinotropic peptide levels and of inhibiting the activity of dipeptidyl peptidase IV.

This study is an extension of 7 controlled phase 3 studies of alogliptin. These phase 3 studies included 1 monotherapy study of alogliptin (SYR-322-PLC-010; NCT00286455); 4 placebo-controlled add-on studies of alogliptin, namely in combination with a sulfonylurea (SYR-322-SULF-007; NCT00286468), metformin (SYR-322-MET-008; NCT00286442), a thiazolidinedione (pioglitazone; SYR-322-TZD-009; NCT00286494), and insulin (SYR-322-INS-011; NCT00286429); 1 coadministration study with pioglitazone in combination with metformin (01-05-TL-322OPI-001; NCT00328627), and 1 coadministration study with pioglitazone (01-06-TL-322OPI-002; NCT00395512).

The end of treatment or early withdrawal visit from the preceding study will be the screening visit for this study, after which enrolled patients will be required to commit to approximately 22 additional visits at the study center.

Eligibility criteria: Inclusion Criteria:

* 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.
* Type 2 diabetes mellitus and was enrolled in one of the following 7 controlled Phase III studies. The study will be open to all patients who completed one of these studies through the end-of-treatment visit:

  * SYR-322-PLC-010 - NCT00286455
  * SYR-322-SULF-007 - NCT00286468
  * SYR-322-MET-008 - NCT00286442
  * SYR-322-TZD-009 - NCT00286494
  * SYR-322-INS-011 - NCT00286429
  * 01-05-TL-322OPI-001 - NCT00328627
  * 01-06-TL-322OPI-002 - NCT00395512
* Alanine aminotransferase less than or equal to 3 times the upper limit of normal and serum creatinine less than or equal to 2.0 mg per dL.
* 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 patient from completing the study.

Exclusion Criteria

* The occurrence of any adverse event or condition during the controlled Phase III studies, which, in the opinion of the investigator, should exclude the patient from participating in the open-label extension.
* 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:

  * Weight-loss drugs
  * Investigational antidiabetics, additional dipeptidyl peptidase-4 (DPP-4) and glucagon-like peptide-1 (GLP 1) inhibitors
  * Incretin Mimetics,
  * Oral or systemically injected glucocorticoids.

Primary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: 4 years
Secondary outcomes:
measure: Change From Baseline Over Time in Glycosylated Hemoglobin
timeFrame: Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45.
measure: Change From Baseline in Fasting Plasma Glucose
timeFrame: Baseline and Year 4
measure: Percentage of Participants With Marked Hyperglycemia
timeFrame: Randomization up to 4 years.
measure: Change From Baseline in Proinsulin Level
timeFrame: Baseline and Year 4
measure: Change From Baseline in Insulin Level
timeFrame: Baseline and Year 4
measure: Change From Baseline in C-peptide Level
timeFrame: Baseline and Year 4
measure: Change From Baseline in Body Weight
timeFrame: Baseline and Year 4
measure: Percentage of Participants With a Clinical Response
timeFrame: Weeks 2, 4, 8, 12, every 3 months up to 4 years, and 1 Day after final dose.
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
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: Los Angeles
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: 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: Hollywood
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Longwood
country: United States
state: Florida
city: New Port Richie
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: 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: 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: Cincinnatti
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: 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: Buenos Aires
country: Argentina
state: La Plata
city: Buenos Aires
country: Argentina
state: Moron
city: Rosario
country: Argentina
state: Sante Fe
city: Buenos Aires
country: Argentina
city: Ciudadd Autonoma de Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: Mar del Plata
country: Argentina
city: Fortaleza
country: Brazil
state: Ceara
city: Curitiba
country: Brazil
state: Parana
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: Mogi das Cruzes
country: Brazil
state: Sao Paulo
city: Santos
country: Brazil
state: Sao Paulo
city: Sao Paulo
country: Brazil
city: Santiago
country: Chile
city: Ostrava
country: Czech Republic
city: Prague
country: Czech Republic
city: Praha
country: Czech Republic
city: Sternberk
country: Czech Republic
city: Zlin
country: Czech Republic
city: Santo Domingo Oeste
country: Dominican Republic
city: Aschaffenburg
country: Germany
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Munich
country: Germany
city: Nuremberg
country: Germany
city: Schwerin
country: Germany
city: Wiesbaden
country: Germany
city: Witten
country: Germany
city: Guatemala
country: Guatemala
city: Almere
country: Netherlands
city: De Bilt
country: Netherlands
city: Geleen
country: Netherlands
city: Oud-Beijerland
country: Netherlands
city: Rotterdam
country: Netherlands
city: Zwijndrecht
country: Netherlands
city: Bellavista
country: Peru
state: Lima
city: San Isidro
country: Peru
state: Lima
city: Ica
country: Peru
city: Lima
country: Peru
city: Bytom
country: Poland
city: Kamieniec Zabkowicki
country: Poland
city: Krakow
country: Poland
city: Leczyca
country: Poland
city: Lodz
country: Poland
city: Radom
country: Poland
city: Pretoria
country: South Africa
state: Gauteng
city: Cape Town
country: South Africa
state: Western Cape
city: Somerset West
country: South Africa
state: Western Cape
city: Durban
country: South Africa
city: Johannesburg
country: South Africa
city: Parow
country: South Africa
Study officials:
affiliation: Takeda
name: VP Biological Sciences
role: STUDY_DIRECTOR
References: