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

NCT02020616 | Terminated Phase 1 Results

• 2 other identifiers: 14515I6I-MC-LMRB
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hemoglobin A1c (HbA1c) at 12-Week Endpoint

  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.

  Baseline, Week 12

Secondary Outcomes (11)

• Percentage of Participants Achieving HbA1c <7.0% or HbA1c ≤6.5% at 12-Week Endpoint

  Week 12

• Percentage of Participants That Require Rescue Therapy

  Baseline through Week 12

• Change From Baseline in Body Weight at 12-Week Endpoint

  Baseline, Week 12

• Change From Baseline in 7-Point Blood Glucose Profile at 12-Week Endpoint

  Baseline, Week 12

• Change From Baseline in Lipids at 12-Week Endpoint

  Baseline, Week 12

Study Arms (4)

LY3053102

EXPERIMENTAL

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; Drug: Metformin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Metformin

Exenatide Extended-Release (ER)

ACTIVE COMPARATOR

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

Drug: Exenatide ER; Drug: Metformin

LY3053102 + Exenatide ER

EXPERIMENTAL

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; Drug: Exenatide ER; Drug: Metformin

Interventions

LY3053102 DRUG

Administered SC

LY3053102; LY3053102 + Exenatide ER

Exenatide ER DRUG

Administered SC

Exenatide Extended-Release (ER); LY3053102 + Exenatide ER

Placebo DRUG

Administered SC

Placebo

Metformin DRUG

Administered orally (PO)

Exenatide Extended-Release (ER); LY3053102; LY3053102 + Exenatide ER; Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

Orange County Research Center

Orange, California, 92868, United States

Location

Miami Research Associates

Miami, Florida, 33143, United States

Location

Compass Research

Orlando, Florida, 32806, United States

Location

Clinilabs, Inc (New York)

New York, New York, 10019, United States

Location

Dallas Diabetes Endocrine Center

Dallas, Texas, 75230, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Stage 2, which was to evaluate participants stratified by HbA1c, metformin therapy, and washout of a second oral anti-hyperglycemic medication (OAM) was not conducted because of inadequate efficacy at well-tolerated doses in Stage 1.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 25, 2013
• Study Start: December 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: October 8, 2019
• Results First Posted: December 20, 2017

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (5)