A Study of LY2189265 Compared to Sitagliptin in Patients With Type 2 Diabetes Mellitus on Metformin


Tracking Information

Start Date  ICMJEAugust 2008
Estimated Primary Completion DateDecember 2011   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: August 12, 2008)		HbA1c change from baseline [ Time Frame: over 12 months ] [ Designated as safety issue: No ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT00734474 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: August 12, 2008)
  • Fasting blood glucose change from baseline [ Time Frame: over 6, 12, and 24 months ] [ Designated as safety issue: No ]
  • Fasting insulin change from baseline [ Time Frame: over 12 and 24 months ] [ Designated as safety issue: No ]
  • Body weight change from baseline [ Time Frame: over 6, 12 and 24 months ] [ Designated as safety issue: Yes ]
  • Waist circumference change from baseline [ Time Frame: over 12 and 24 months ] [ Designated as safety issue: Yes ]
  • Proportion of patients who achieve an HbA1c <7% or < or = 6.5% [ Time Frame: over 12 and 24 months ] [ Designated as safety issue: No ]
  • Incidence of hypoglycemic episodes [ Time Frame: over 6, 12 and 24 months ] [ Designated as safety issue: Yes ]
  • Beta cell function and insulin sensitivity (HOMA2) [ Time Frame: over 12 and 24 months ] [ Designated as safety issue: No ]
  • Safety: laboratory tests, lipids parameter, TEAEs, vital signs, and ECG parameters [ Time Frame: over 6, 12 and 24 months ] [ Designated as safety issue: Yes ]
  • Patient-reported outcomes (IWQoL-Lite) [ Time Frame: over 12 and 24 months ] [ Designated as safety issue: No ]
  • Patient-reported outcomes (EQ-5D) [ Time Frame: over 12 and 24 months ] [ Designated as safety issue: No ]
  • Resource utilization [ Time Frame: over 12 and 24 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of LY2189265 [ Time Frame: over 24 months ] [ Designated as safety issue: Yes ]
  • Antibodies to LY2189265 [ Time Frame: over 24 months ] [ Designated as safety issue: Yes ]
  • HbA1c change from baseline [ Time Frame: over 6 and 24 months ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures  ICMJESame as current

Descriptive Information

Brief Title  ICMJEA Study of LY2189265 Compared to Sitagliptin in Patients With Type 2 Diabetes Mellitus on Metformin
Official Title  ICMJEA Phase 2/3, Placebo-Controlled, Efficacy and Safety Study of Once-Weekly, Subcutaneous LY2189265 Compared to Sitagliptin in Patients With Type 2 Diabetes Mellitus on Metformin
Brief Summary

This is an adaptive dose finding study and a phase 3 efficacy study to evaluate the effects of once weekly injection of LY2189265 compared to sitagliptin on glucose by measuring HbA1c change from baseline after twelve months in patients with type 2 diabetes mellitus on metformin.

Detailed Description 
Study PhasePhase II, Phase III
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study
Condition  ICMJEDiabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: LY2189265
    Subcutaneous injection once-weekly for up to 24 months
  • Drug: Sitagliptin 100mg, 24 months
    One tablet by mouth daily for up to 24 months
  • Drug: Placebo solution
    Subcutaneous injection once weekly for up to 24 months
  • Drug: Placebo tablet, 6 months
    One tablet by mouth daily for up to 6 months
  • Drug: Placebo tablet, 24 months
    One tablet by mouth daily for up to 24 months
  • Drug: Sitagliptin 100 mg, 18 months
    One tablet by mouth daily for up to 18 months
Study Arms / Comparison Groups
  • 1: Experimental
    0.25 mg LY2189265 Subcutaneous (SC) once weekly (QW) and placebo tablet 1 po qd
    Interventions:
    • Drug: LY2189265
    • Drug: Placebo tablet, 24 months
  • 2: Experimental
    0.50 mg LY2189265 SC QW and placebo tablet 1 po qd
    Interventions:
    • Drug: LY2189265
    • Drug: Placebo tablet, 24 months
  • 3: Experimental
    0.75 mg LY2189265 SC QW and placebo tablet 1 po qd
    Interventions:
    • Drug: LY2189265
    • Drug: Placebo tablet, 24 months
  • 4: Experimental
    1.00 mg LY2189265 SC QW and placebo tablet 1 po qd
    Interventions:
    • Drug: LY2189265
    • Drug: Placebo tablet, 24 months
  • 5: Experimental
    1.50 mg LY2189265 SC QW and placebo tablet 1 po qd
    Interventions:
    • Drug: LY2189265
    • Drug: Placebo tablet, 24 months
  • 6: Experimental
    2.00 mg LY2189265 SC QW and placebo tablet 1 po qd
    Interventions:
    • Drug: LY2189265
    • Drug: Placebo tablet, 24 months
  • 7: Experimental
    3.00 mg LY2189265 SC QW and placebo tablet 1 po qd
    Interventions:
    • Drug: LY2189265
    • Drug: Placebo tablet, 24 months
  • 8: Active Comparator
    Sitagliptin 100 mg one tablet po qd and placebo solution injected SC QW
    Interventions:
    • Drug: Sitagliptin 100mg, 24 months
    • Drug: Placebo solution
  • 9: Placebo Comparator
    Placebo tablet 1 po qd and placebo solution injected SC QW then after 6 months sitagliptin 100 mg one tablet po qd and placebo solution injected SC QW
    Interventions:
    • Drug: Placebo solution
    • Drug: Placebo tablet, 6 months
    • Drug: Sitagliptin 100 mg, 18 months

Recruitment Information

Estimated Enrollment  ICMJE1566
Estimated Completion DateAugust 2012
Estimated Primary Completion DateDecember 2011   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diabetes mellitus, type 2 for at least 6 months
  • Treatment regimens: diet and exercise, metformin as monotherapy or in combination with another oral antihyperglycemic medication (OAM), or another OAM as monotherapy. Must be able to tolerate metformin at a dose of at least 1500 mg daily for 6 weeks prior to randomization.
  • HbA1c value of ≥7.0% to ≤9.5%
  • Body mass index (BMI) between 25 and 40 kg/m2, inclusive
  • Stable weight for 3 months prior to screening
  • Females of childbearing potential must test negative for pregnancy and agree to use a reliable birth control method

Exclusion Criteria:

  • Diabetes mellitus, type 1
  • Use of a GLP-1 analog (for example, exenatide) within 6 months prior to screening or are being treated with insulin
  • Gastric emptying abnormality, history of bariatric surgery or chronic use of drugs that affect gastrointestinal motility
  • Use of medications to promote weight loss
  • Cardiovascular event within 6 months prior to screening
  • Poorly controlled hypertension
  • ECG reading considered outside the normal limits or indicating cardiac disease
  • Liver disease, hepatitis, chronic pancreatitis, idiopathic acute pancreatitis, or alanine transaminase (ALT) levels >3.0 times the upper limit of normal
  • Serum creatinine ≥1.5 mg/dL or a creatinine clearance < 60 ml/minute
  • Uncontrolled diabetes
  • Uncontrolled endocrine or autoimmune abnormality
  • History of a transplanted organ
  • Chronic use of systemic glucocorticoid therapy
  • Active or untreated malignancy
  • Use of CNS stimulants
GenderBoth
Ages18 Years to 75 Years
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY(1-877-285-4559) or1-317-615-4559
Location Countries  ICMJEUnited States,   Canada,   France,   Germany,   India,   Korea, Republic of,   Mexico,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Spain,   Taiwan,   United Kingdom

Administrative Information

NCT ID  ICMJENCT00734474
Responsible PartyChief Medical Officer, Eli Lilly and Company
Study ID Numbers  ICMJE11422, H9X-MC-GBCF, CTRI/2009/091/000969
Study Sponsor  ICMJEEli Lilly and Company
Collaborators  ICMJE
  • United BioSource Corporation
  • Tessella Inc.
  • Berry Consultants
Investigators  ICMJE
Study Chair: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
Information Provided ByEli Lilly and Company