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

• ClinicalTrials.gov Identifier: NCT02020616
• Recruitment Status: Terminated
• First Posted: December 25, 2013
• Results First Posted: December 20, 2017
• Last Update Posted: October 8, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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 Design

• 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

Arms and Interventions

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)

Outcome Measures

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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• 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

Contacts and Locations

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

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02020616
• Other Study ID Numbers: 14515; I6I-MC-LMRB ( Other Identifier: Eli Lilly and Company )
• First Posted: December 25, 2013
• Results First Posted: December 20, 2017
• Last Update Posted: October 8, 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:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metformin; Exenatide; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Obesity Agents; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists