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

Lilly

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: LY3053102; Drug: Exenatide ER; Drug: Metformin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02020616

14515

I6I-MC-LMRB (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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60 participants in 4 patient groups, including a placebo group

LY3053102

Experimental group

Description:

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

Treatment:

Drug: LY3053102

Drug: Metformin

Placebo

Placebo Comparator group

Description:

Stage 1 and Stage 2: Placebo to match LY3053102 administered by SC injection once a week for 12 weeks

Treatment:

Drug: Placebo

Drug: Metformin

Exenatide Extended-Release (ER)

Active Comparator group

Description:

Stage 1 and Stage 2: Exenatide ER 2 mg given by SC injection once a week for 12 weeks

Treatment:

Drug: Exenatide ER

Drug: Metformin

LY3053102 + Exenatide ER

Experimental group

Description:

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

Treatment:

Drug: LY3053102

Drug: Exenatide ER

Drug: Metformin