Clinical trial NCT02020616: A Study of the Safety and Effectiveness of LY3053102 in Participants With Type 2 Diabetes
Official title: Safety, Tolerability, Pharmacokinetics, and Efficacy of LY3053102 With 12 Weeks of Treatment in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-12-25
Enrollment: 60
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at 12-Week Endpoint
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving HbA1c <7.0% or HbA1c ≤6.5% at 12-Week Endpoint
timeFrame: Week 12
measure: Percentage of Participants That Require Rescue Therapy
timeFrame: Baseline through Week 12
measure: Change From Baseline in Body Weight at 12-Week Endpoint
timeFrame: Baseline, Week 12
measure: Change From Baseline in 7-Point Blood Glucose Profile at 12-Week Endpoint
timeFrame: Baseline, Week 12
measure: Change From Baseline in Lipids at 12-Week Endpoint
timeFrame: Baseline, Week 12
measure: Percentage of Participants With Anti-Drug Antibodies to LY3053102
timeFrame: Baseline through Study Completion (Up to 6 Months)
measure: Percentage of Participants With Hypoglycemia
timeFrame: Baseline through Week 12
measure: Change From Baseline in Bone Metabolism at 12-Week Endpoint (Osteocalcin and Bone-Specific Alkaline Phosphatase [Bone-Specific ALP])
timeFrame: Baseline, Week 12
measure: Change From Baseline in Bone Metabolism at 12-Week Endpoint (Beta-Crosslaps and Procollagen 1 N-Terminal Propeptide [P1NP])
timeFrame: Baseline, Week 12
measure: Change From Baseline in Bone Mineral Density Markers at 12-Week Endpoint
timeFrame: Baseline, Week 12
measure: Pharmacokinetics: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC [τ,ss]) of LY3053102
timeFrame: Predose, 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168 hours post-dose
Other outcomes:
Locations:
city: Orange
country: United States
facility: Orange County Research Center
state: California
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: New York
country: United States
facility: Clinilabs, Inc (New York)
state: New York
city: Dallas
country: United States
facility: Dallas Diabetes Endocrine Center
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM -5PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: