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A Study of the Safety and Effectiveness of LY3053102 in Participants With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT02020616
Recruitment Status : Terminated (Lack of Efficacy)
First Posted : December 25, 2013
Results First Posted : December 20, 2017
Last Update Posted : December 20, 2017
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The purpose of this study is to investigate the safety and effectiveness of the study drug known as LY3053102 in participants with Type 2 diabetes mellitus. The study drug will be given in different doses as an injection under the skin. The study is expected to last up to 6 months for each participant. Participants may remain on stable-dose metformin as prescribed by their personal physician.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: LY3053102 Drug: Exenatide ER Drug: Placebo Drug: Metformin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety, Tolerability, Pharmacokinetics, and Efficacy of LY3053102 With 12 Weeks of Treatment in Patients With Type 2 Diabetes Mellitus
Study Start Date : December 2013
Actual Primary Completion Date : February 2015
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide
U.S. FDA Resources

Arm Intervention/treatment
Experimental: LY3053102
Stage 1: Escalating dose (7 milligrams [mg] up to 200 mg) of LY3053102 administered once a week by subcutaneous (SC) injection for 12 weeks. Stage 2: LY3053102 administered once a week by SC injection for 12 weeks
Drug: LY3053102
Administered SC
Drug: Metformin
Administered orally (PO)
Placebo Comparator: Placebo
Stage 1 and Stage 2: Placebo to match LY3053102 administered by SC injection once a week for 12 weeks
Drug: Placebo
Administered SC
Drug: Metformin
Administered orally (PO)
Active Comparator: Exenatide Extended-Release (ER)
Stage 1 and Stage 2: Exenatide ER 2 mg given by SC injection once a week for 12 weeks
Drug: Exenatide ER
Administered SC
Drug: Metformin
Administered orally (PO)
Experimental: LY3053102 + Exenatide ER
Stage 2: LY3053102 administered by SC injection once a week for 12 weeks and exenatide ER 2 mg administered by SC injection once a week for 12 weeks
Drug: LY3053102
Administered SC
Drug: Exenatide ER
Administered SC
Drug: Metformin
Administered orally (PO)



Primary Outcome Measures :
  1. Change From Baseline in Hemoglobin A1c (HbA1c) at 12-Week Endpoint [ Time Frame: Baseline, Week 12 ]
    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) analysis adjusting for metformin use, washout of second oral anti-hyperglycemic medication (OAM), treatment, visit, and treatment-by-visit interaction as fixed effects, baseline as a covariate, and participant as a random effect.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving HbA1c <7.0% or HbA1c ≤6.5% at 12-Week Endpoint [ Time Frame: Week 12 ]
    HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

  2. Percentage of Participants That Require Rescue Therapy [ Time Frame: Baseline through Week 12 ]
    Percentage of participants that required >=1 rescue (blood glucose lowering) medications.

  3. Change From Baseline in Body Weight at 12-Week Endpoint [ Time Frame: Baseline, Week 12 ]
    LS means were calculated using MMRM analysis adjusting for baseline HbA1c category, metformin use, washout of second OAM, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline as a covariate, and participant as a random effect (excludes data after rescue therapy).

  4. Change From Baseline in 7-Point Blood Glucose Profile at 12-Week Endpoint [ Time Frame: Baseline, Week 12 ]
    7-Point Self-Monitored Blood Glucose profiles are measures of blood glucose concentration taken 7 times a day at morning pre-prandial, morning 2 hours postprandial, midday pre-prandial, midday 2 hours postprandial, evening pre-prandial, evening 2 hour postprandial, and bedtime. LS means were calculated using MMRM analysis adjusting for baseline HbA1c category, metformin use, washout of second OAM, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline as a covariate, and participant as a random effect (excludes data after rescue therapy).

  5. Change From Baseline in Lipids at 12-Week Endpoint [ Time Frame: Baseline, Week 12 ]
    Lipids includes: High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol (LDL-C), Triglycerides, and Cholesterol. LS means were calculated using MMRM analysis adjusting for metformin use, washout of second OAM, baseline HbA1c category, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline as a covariate, and participant as a random effect (excludes data after rescue therapy).

  6. Percentage of Participants With Anti-Drug Antibodies to LY3053102 [ Time Frame: Baseline through Study Completion (Up to 6 Months) ]
    Percentage of participants with anti-LY3053102 antibody titre changes from baseline to the maximum postbaseline value.

  7. Percentage of Participants With Hypoglycemia [ Time Frame: Baseline through Week 12 ]
    Hypoglycemia was defined as any event meeting the criteria for documented symptomatic hypoglycemia, asymptomatic hypoglycemia, or probable symptomatic hypoglycemia.

  8. Change From Baseline in Bone Metabolism at 12-Week Endpoint (Osteocalcin and Bone-Specific Alkaline Phosphatase [Bone-Specific ALP]) [ Time Frame: Baseline, Week 12 ]
    LS means were calculated using MMRM analysis adjusting for metformin use, washout of second OAM, baseline HbA1c category, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline as a covariate, and participant as a random effect (excludes data after rescue therapy).

  9. Change From Baseline in Bone Metabolism at 12-Week Endpoint (Beta-Crosslaps and Procollagen 1 N-Terminal Propeptide [P1NP]) [ Time Frame: Baseline, Week 12 ]
    LS means were calculated using MMRM analysis adjusting for metformin use, washout of second OAM, baseline HbA1c category, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline as a covariate, and participant as a random effect (excludes data after rescue therapy).

  10. Change From Baseline in Bone Mineral Density Markers at 12-Week Endpoint [ Time Frame: Baseline, Week 12 ]
    LS means were calculated using MMRM analysis adjusting for metformin use, washout of second OAM, baseline HbA1c category, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline as a covariate, and participant as a random effect (excludes data after rescue therapy).

  11. Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC [τ,ss]) of LY3053102 [ Time Frame: Predose, 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 hours post-dose ]
    AUC (τ,ss) = area under the concentration versus time curve during one dosing interval at steady state, where the dosing interval (τ) = 168 hours.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Participants with type 2 diabetes mellitus for at least 6 months before entering the trial based on the disease diagnostic criteria (World Health Organization [WHO]) classification managed with diet or exercise alone or with a stable dose of metformin of at least 1000 mg/day for at least 60 days before screening or on metformin and an eligible second oral anti-hyperglycemic medication after a 60-day washout of the second oral anti-hyperglycemic medication
  • Women not of childbearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause
  • Have a hemoglobin A1c value of ≥7.0% and ≤10.5%, if on diet and exercise or diet, exercise, and metformin (stable dose of at least 1000 mg/day for at least 60 days), or have a hemoglobin A1c value of ≥7.0% and ≤9.5%, and are on an appropriate diet and exercise regimen, a stable dose of metformin and willing to discontinue a second oral anti-hyperglycemic medication
  • Have a body mass index ≥23 and ≤45 kilograms per square meter (kg/m^2)

Exclusion Criteria

  • Have used insulin for diabetic control for more than 6 consecutive days within 1 year prior to screening
  • Have used thiazolidinediones within 3 months, or any other drugs for treatment of hyperglycemia (except metformin) within 2 months, prior to the first week of the study
  • Have hepatitis B and/or positive hepatitis B surface antigen. hepatitis C or human immunodeficiency virus (HIV) and/or positive HIV antibodies
  • Have known or suspected cardiac autonomic neuropathy (for example, resting tachycardia or orthostatic hypotension), based on clinical signs, symptoms, or appropriate diagnostic testing
  • Have cardiac disease with functional status that is New York Heart Association Class II, III, or IV or in the last 6 months have had any of the following: a history of myocardial infarction , unstable angina, coronary artery bypass graft, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack, or cerebrovascular accident (for example, stroke)
  • Have poorly controlled hypertension, malignant hypertension, renal artery stenosis, and/or evidence of labile blood pressure including symptomatic postural hypotension. Doses of antihypertensive medications must be stable for 30 days prior to the first week of the study
  • Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or an alanine transaminase or aspartate aminotransferase levels >2 times the upper limit of the reference range
  • Have evidence of hypothyroidism or hyperthyroidism based on clinical evaluation and/or an abnormal thyroid-stimulating hormone which, in the opinion of the investigator, would pose a risk to participant safety. Participants on a stable dose of thyroid replacement therapy may be eligible if they meet the other criteria
  • Have clinically significant peripheral vascular disease, or clinical evidence of active diabetic proliferative retinopathy, (known significant autonomic neuropathy) as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis
  • Have an active or untreated malignancy or have been in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years
  • Have impaired renal function
  • Have fasting triglycerides >500 milligrams per deciliter (mg/dL) at screening
  • Have experienced a keto-acidotic episode requiring hospitalization in the last 6 months
  • Have an electrocardiogram (ECG) considered to be indicative of cardiac disease
  • Have personal or family history of long QT syndrome, family history of sudden death in a first-degree relative before age 40, or personal history of unexplained syncope within the last year. Use of prescription or over-the-counter medications known to prolong the QT or QTc interval
  • Have a history of bone disease (including osteoporosis or unhealed fractures), evidence of osteoporosis (femoral neck or lumbar spine T-score <-2.5) determined by dual X-ray absorptometry (DXA) scan at screening, evidence of osteopenia (T-score between -1.0 and -2.5 at the femoral neck or lumbar spine) with a high risk of fracture based on risk factors or current active treatment of periodontal disease

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): NCT02020616


Locations
United States, California
Orange County Research Center
Orange, California, United States, 92868
United States, Florida
Miami Research Associates
Miami, Florida, United States, 33143
Compass Research
Orlando, Florida, United States, 32806
United States, New York
Clinilabs, Inc (New York)
New York, New York, United States, 10019
United States, Texas
Dallas Diabetes Endocrine Center
Dallas, Texas, United States, 75230
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM -5PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02020616     History of Changes
Other Study ID Numbers: 14515
I6I-MC-LMRB ( Other Identifier: Eli Lilly and Company )
First Posted: December 25, 2013    Key Record Dates
Results First Posted: December 20, 2017
Last Update Posted: December 20, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.


Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists