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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Takeda
ClinicalTrials.gov Identifier:
NCT00306384
First received: March 21, 2006
Last updated: February 17, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus
Drug: Alogliptin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Fasting Plasma Glucose [ Time Frame: Baseline and Year 4 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Marked Hyperglycemia [ Time Frame: Randomization up to 4 years. ] [ Designated as safety issue: No ]

    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).


  • Change From Baseline in Proinsulin Level [ Time Frame: Baseline and Year 4 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Insulin Level [ Time Frame: Baseline and Year 4 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in C-peptide Level [ Time Frame: Baseline and Year 4 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Body Weight [ Time Frame: Baseline and Year 4 ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: No ]

    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%.


Enrollment: 3323
Study Start Date: March 2006
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alogliptin 12.5 mg
Alogliptin 12.5 tablet, orally, once daily for up to 4 years.
Drug: Alogliptin
Alogliptin tablets.
Other Names:
  • SYR110322
  • SYR-322
Experimental: Alogliptin 25 mg
Alogliptin 25 mg tablet, orally, once daily for up to 4 years.
Drug: Alogliptin
Alogliptin tablets.
Other Names:
  • SYR110322
  • SYR-322

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00306384

  Show 115 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Study Director: VP Biological Sciences Takeda
  More Information

No publications provided

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT00306384     History of Changes
Other Study ID Numbers: SYR-322-OLE-012, 2005-004672-20, U1111-1113-8455
Study First Received: March 21, 2006
Results First Received: February 17, 2013
Last Updated: February 17, 2013
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
Czech Republic: State Institute for Drug Control
Estonia: The State Agency of Medicine
Latvia: State Agency of Medicines
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Takeda:
Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus,
Lipoatrophic
Dyslipidemia
Drug Therapy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Alogliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014