Long-term Safety of Alogliptin in Patients With Type 2 Diabetes Mellitus

February 17, 2013 updated by: Takeda

A Long-Term, Open-Label Extension Study to Investigate the Long-Term Safety of SYR110322 (SYR-322) in Subjects With Type 2 Diabetes

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

3323

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
      • Ciudadd Autonoma de Buenos Aires, Argentina
      • Cordoba, Argentina
      • Mar del Plata, Argentina
    • La Plata
      • Buenos Aires, La Plata, Argentina
    • Moron
      • Buenos Aires, Moron, Argentina
    • Sante Fe
      • Rosario, Sante Fe, Argentina
  • Brazil
      • Sao Paulo, Brazil
    • Ceara
      • Fortaleza, Ceara, Brazil
    • Parana
      • Curitiba, Parana, Brazil
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil
    • Sao Paulo
      • Mogi das Cruzes, Sao Paulo, Brazil
      • Santos, Sao Paulo, Brazil
  • Chile
      • Santiago, Chile
  • Czech Republic
      • Ostrava, Czech Republic
      • Prague, Czech Republic
      • Praha, Czech Republic
      • Sternberk, Czech Republic
      • Zlin, Czech Republic
  • Dominican Republic
      • Santo Domingo Oeste, Dominican Republic
  • Germany
      • Aschaffenburg, Germany
      • Berlin, Germany
      • Frankfurt, Germany
      • Hamburg, Germany
      • Hannover, Germany
      • Munich, Germany
      • Nuremberg, Germany
      • Schwerin, Germany
      • Wiesbaden, Germany
      • Witten, Germany
  • Guatemala
      • Guatemala, Guatemala
  • Netherlands
      • Almere, Netherlands
      • De Bilt, Netherlands
      • Geleen, Netherlands
      • Oud-Beijerland, Netherlands
      • Rotterdam, Netherlands
      • Zwijndrecht, Netherlands
  • Peru
      • Ica, Peru
      • Lima, Peru
    • Lima
      • Bellavista, Lima, Peru
      • San Isidro, Lima, Peru
  • Poland
      • Bytom, Poland
      • Kamieniec Zabkowicki, Poland
      • Krakow, Poland
      • Leczyca, Poland
      • Lodz, Poland
      • Radom, Poland
  • South Africa
      • Durban, South Africa
      • Johannesburg, South Africa
      • Parow, South Africa
    • Gauteng
      • Pretoria, Gauteng, South Africa
    • Western Cape
      • Cape Town, Western Cape, South Africa
      • Somerset West, Western Cape, South Africa
  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • Arizona
      • Peoria, Arizona, United States
      • Phoenix, Arizona, United States
    • California
      • Anaheim, California, United States
      • Artesia, California, United States
      • Fresno, California, United States
      • Los Angeles, California, United States
      • Mission Viejo, California, United States
      • Northridge, California, United States
      • Orange, California, United States
      • San Diego, California, United States
      • Tustin, California, United States
      • Walnut Creek, California, United States
    • Colorado
      • Colorado Springs, Colorado, United States
      • Denver, Colorado, United States
    • Connecticut
      • Norwalk, Connecticut, United States
    • District of Columbia
      • Washington, District of Columbia, United States
    • Florida
      • Clearwater, Florida, United States
      • Hollywood, Florida, United States
      • Kissimmee, Florida, United States
      • Longwood, Florida, United States
      • New Port Richie, Florida, United States
      • Ocala, Florida, United States
      • Ocoee, Florida, United States
      • St. Cloud, Florida, United States
    • Georgia
      • Lawrenceville, Georgia, United States
    • Hawaii
      • Honolulu, Hawaii, United States
    • Idaho
      • Idaho Falls, Idaho, United States
    • Illinois
      • Chicago, Illinois, United States
    • Indiana
      • Avon, Indiana, United States
      • Elkhart, Indiana, United States
      • Evansville, Indiana, United States
      • Lafayette, Indiana, United States
    • Kentucky
      • Erlanger, Kentucky, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Massachusetts
      • Sudbury, Massachusetts, United States
    • Missouri
      • Chesterfield, Missouri, United States
      • St. Louis, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • New Jersey
      • Berlin, New Jersey, United States
    • North Carolina
      • Burlington, North Carolina, United States
      • Charlotte, North Carolina, United States
      • Morehead City, North Carolina, United States
      • Pinehurst, North Carolina, United States
      • Winston-Salem, North Carolina, United States
    • Ohio
      • Cincinnatti, Ohio, United States
      • Dayton, Ohio, United States
    • Oklahoma
      • Tulsa, Oklahoma, United States
    • Oregon
      • Medford, Oregon, United States
    • Pennsylvania
      • Lansdale, Pennsylvania, United States
      • West Grove, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
      • Columbia, South Carolina, United States
      • Simpsonville, South Carolina, United States
    • Tennessee
      • Bristol, Tennessee, United States
      • Cookeville, Tennessee, United States
      • Milan, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • San Antonio, Texas, United States
      • Temple, Texas, United States
      • Texarkana, Texas, United States
    • Vermont
      • Burlington, Vermont, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Alogliptin 12.5 mg
Alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Drug: Alogliptin
Alogliptin tablets.
Other Names:
  • SYR-322
  • SYR110322
Experimental: Alogliptin 25 mg
Alogliptin 25 mg tablet, orally, once daily for up to 4 years.
Drug: Alogliptin
Alogliptin tablets.
Other Names:
  • SYR-322
  • SYR110322

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame: 4 years
Safety was assessed by physical examinations, clinical laboratory parameters, electrocardiogram (ECG) readings, vital sign measurements, oral temperature, and hypoglycemic events. Changes in laboratory values or ECG parameters were considered to be adverse events if they were judged to be clinically significant. A TEAE was any event that started on or after the first dose of open-label study drug and within 14 days after the last dose.
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline Over Time in Glycosylated Hemoglobin
Time Frame: Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45.
The change from Baseline in glycosylated hemoglobin (HbA1c; the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) during the study. Endpoint was defined as the last postbaseline observation collected within 7 days after the last dose of open-label study drug.
Baseline and Month 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45.
Change From Baseline in Fasting Plasma Glucose
Time Frame: Baseline and Year 4
The change from Baseline in fasting plasma glucose (FPG) at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Baseline and Year 4
Percentage of Participants With Marked Hyperglycemia
Time Frame: Randomization up to 4 years.

Marked Hyperglycemia is defined as fasting plasma glucose greater than or equal to 200 mg/dL (≥11.10 mmol/L).

The Month 42 to Month 45 interval includes all marked hyperglycemic episodes occurring on or after Day 1247 (a 203-day visit window).
Randomization up to 4 years.
Change From Baseline in Proinsulin Level
Time Frame: Baseline and Year 4

Proinsulin is a precursor to insulin, and was measured as an indicator of pancreatic function. The change from Baseline in fasting proinsulin to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.

Note: A transcription error occurred in the reporting of 1 proinsulin value for a patient in the alogliptin 25 mg completed group, for whom a partial patient ID number was mistakenly entered as an end-of-treatment proinsulin level.
Baseline and Year 4
Change From Baseline in Insulin Level
Time Frame: Baseline and Year 4
The change from Baseline in fasting insulin at the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Baseline and Year 4
Change From Baseline in C-peptide Level
Time Frame: Baseline and Year 4
C-peptide is a byproduct created when the hormone insulin is produced and is measured by a blood test. Change from Baseline to the last post-baseline observation, collected within 7 days after the last dose of open-label study drug.
Baseline and Year 4
Change From Baseline in Body Weight
Time Frame: Baseline and Year 4
Change from Baseline in body weight to the last post-baseline observation collected within 7 days after the last dose of open-label study drug.
Baseline and Year 4
Percentage of Participants With a Clinical Response
Time Frame: Weeks 2, 4, 8, 12, every 3 months up to 4 years, and 1 Day after final dose.

Clinical response was defined based on the absolute value of HbA1c meeting one of two clinical targets at any post-baseline visit:

  • HbA1c ≤6.5%;
  • HbA1c ≤7.0%.
Weeks 2, 4, 8, 12, every 3 months up to 4 years, and 1 Day after final dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Takeda

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

March 21, 2006

First Submitted That Met QC Criteria

March 21, 2006

First Posted (Estimate)

March 23, 2006

Study Record Updates

Last Update Posted (Estimate)

March 22, 2013

Last Update Submitted That Met QC Criteria

February 17, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SYR-322-OLE-012
  • 2005-004672-20 (EudraCT Number)
  • U1111-1113-8455 (Registry Identifier: WHO)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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