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A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02111096
Recruitment Status : Terminated (The overall benefit-risk profile did not support continued development of LY2409021 for type 2 diabetes.)
First Posted : April 10, 2014
Results First Posted : April 24, 2018
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The intent of this study is to assess the safety of LY2409021 in participants with Type 2 diabetes mellitus taking metformin and sulfonylurea as prescribed by their personal physician. The study treatment is expected to last 12 months (52 weeks).

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: LY2409021 Drug: Sitagliptin Drug: Placebo Drug: Metformin Drug: Sulfonylurea Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 2, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of LY2409021 Compared to Sitagliptin in Subjects With Type 2 Diabetes Mellitus
Study Start Date : April 2014
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LY2409021
20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Drug: LY2409021
Administered orally

Drug: Metformin
Administered orally

Drug: Sulfonylurea
Administered orally

Active Comparator: Sitagliptin
100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Drug: Sitagliptin
Administered orally

Drug: Metformin
Administered orally

Drug: Sulfonylurea
Administered orally

Placebo Comparator: Placebo
Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Drug: Placebo
Administered orally

Drug: Metformin
Administered orally

Drug: Sulfonylurea
Administered orally




Primary Outcome Measures :
  1. Change From Baseline to 6 Months in Hepatic Fat Fraction [ Time Frame: Baseline, 6 months ]
    The hepatic fat fraction (HFF) was calculated by a core imaging laboratory from noncontrast magnetic resonance imaging (MRI) of the liver. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.


Secondary Outcome Measures :
  1. Change From Baseline to 6 Months in Alanine Aminotransferase Levels [ Time Frame: Baseline, 6 months ]
    Alanine aminotransferase (ALT) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

  2. Number of Participants With Hepatobiliary Adverse Events of Special Interest (AESI) [ Time Frame: Baseline, 6 months ]
    Number of participants with ALT or AST greater than 3 times the upper limit of normal at a post-baseline visit. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

  3. Change From Baseline to 6 Months in Fasting Lipids Levels [ Time Frame: Baseline, 6 months ]
    Lipid values (cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

  4. Change From Baseline to 6 Months in Fasting Blood Glucagon [ Time Frame: Baseline, 6 months ]
    Glucagon values assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

  5. Change From Baseline to 6 Months in Body Weight [ Time Frame: Baseline, 6 months ]
    Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

  6. Change From Baseline to 6 Months in Hemoglobin A1c (HbA1c) [ Time Frame: Baseline, 6 months ]
    HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, visit, baseline score, and treatment-by-visit.

  7. Change From Baseline to 6 Months in Fasting Plasma Glucose [ Time Frame: Baseline, 6 months ]
    Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

  8. Change From Baseline to 6 Months in Blood Pressure [ Time Frame: Baseline, 6 months ]
    Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured in triplicate throughout the study. At each visit, all available blood pressure measurements for a subject were averaged to provide the blood pressure for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

  9. Change From Baseline to 6 Months in Pulse Rate [ Time Frame: Baseline, 6 months ]
    Seated pulse rate was measured in triplicate throughout the study. At each visit, all available pulse measurements for a subject were averaged to provide the pulse for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

  10. Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) [ Time Frame: Baseline, 6 months ]
    7-point profile consists of pre-meal and 2-hour postprandial SMBG measurements for the morning, midday, and evening meals in 1 day and at 3 AM (nocturnal blood glucose measurement). Pre-meal measurements were taken before the subject began eating the meal. Participants recorded their glucose measurements in their study diaries.

  11. Population Pharmacokinetics: Apparent Clearance of LY2409021 [ Time Frame: Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose, ]
    Reported as a Population Estimate with % Standard Errors of Estimation (SEE), 5th-95th confidence interval.

  12. Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021 [ Time Frame: Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose, ]
  13. Rate of Hypoglycemic Events Adjusted Per 30 Days [ Time Frame: Baseline through 6 months ]
    Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L),is presented. Rate: (30 days) is calculated as: (number of episodes during the time period divided by the number of days during the time period) multiplied by 30.

  14. Number of Participants With Hypoglycemic Events [ Time Frame: Baseline through 6 months ]
    Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L), is presented. The number of subjects with an event are subjects who had at least one episode of documented symptomatic hypoglycemia during the time period.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have been treated with a stable dose of metformin for at least 3 months and have been treated with an optimally effective and stable dose of an sulfonylurea for at least 6 months prior to screening.
  • HbA1c value between 7.0% and 10.0%, inclusive.
  • Body mass index (BMI) between 20 and 45 kilograms/square meter (kg/m^2), inclusive.

Exclusion Criteria:

  • Known type 1 diabetes mellitus.
  • More than 1 episode of severe hypoglycemia within 6 months prior to screening.
  • Two or more emergency room visits or hospitalizations due to poor glucose control in the 6 months prior to screening.
  • Severe gastrointestinal disease that may significantly impact gastric emptying or motility or having undergone gastric bypass or gastric banding surgery.
  • Previous history or active diagnosis of pancreatitis.
  • Positive hepatitis B surface antigen or hepatitis C antibody.
  • Clinical signs or symptoms of liver disease, or hepatic aminotransferases (aminotransferase or alanine aminotransferase) greater than 2.0× upper limit of normal (ULN) or elevated alkaline phosphatase (greater than ULN) unrelated to bone metabolic disease.
  • Elevated total bilirubin level (greater than ULN), clinically suspicious signs/symptoms of cirrhosis or history of cirrhosis.
  • Current diagnosis, personal history of neuroendocrine tumors, family history of any type of multiple endocrine neoplasia (MEN), or Von Hippel-Lindau.
  • Contraindications for magnetic resonance imaging.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02111096


Locations
Show Show 33 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02111096    
Other Study ID Numbers: 15286
I1R-MC-GLDJ ( Other Identifier: Eli Lilly and Company )
2013-004275-12 ( EudraCT Number )
First Posted: April 10, 2014    Key Record Dates
Results First Posted: April 24, 2018
Last Update Posted: October 9, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action