A Study of LY2405319 in Participants With Type 2 Diabetes

Lilly

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: LY2405319; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01869959

12708

I1K-MC-GLUG (Other Identifier)

Details and patient eligibility

About

The main purpose of this study was to evaluate the safety and tolerability of LY2405319. It was given as a daily injection under the skin to participants with type 2 diabetes mellitus (T2DM) for 28 days. This study determined how long the drug stays in the body and how it affects blood sugar levels. After screening, the study lasted about 2 months for each participant. Participants continued their prestudy regimen of diet and exercise alone or in combination with metformin.

Enrollment: 47 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a diagnosis of T2DM.
• Are on diet and exercise or diet, exercise, and metformin (stable dose of at least 1000 mg/day for at least 60 days) regimen.
• Have a glycosylated hemoglobin A1c (HbA1c) value of 7.0% to 10.0%, inclusive, or are on metformin and an additional oral antidiabetic medication (OAM) with an HbA1c value of 6.5% to 9.5%, inclusive.
• Participants on another OAM in addition to metformin therapy may be randomized if removed from treatment of the other OAM ≥14 days prior to study drug administration and fasting blood glucose is ≥145 mg per deciliter (mg/dL) and ≤270 mg/dL.
• Are females not of child-bearing potential due to surgical sterilization or are postmenopausal.
• Have a body mass index (BMI) ≥25 and ≤40.
• Have clinical laboratory test results within normal reference range for the population.

Exclusion criteria

• Use insulin, thiazolidinediones (TZDs), dipeptidyl peptidase (DPP) IV inhibitors, or exenatide during the 3 months prior to screening.
• Have had more than 1 episode of severe hypoglycemia requiring assistance of another person to administer a resuscitative action within 6 months prior to entry into the study or are currently diagnosed with having hypoglycemia unawareness.
• Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.
• Have any abnormality of the electrocardiogram (ECG) that will, in the opinion of the investigator, impair the ability to measure the QT (a corrected QC [QTc] [Bazett's correction] interval >450 milliseconds [msec] for men and >470 msec for women or a PR interval >220 msec are specifically excluded) or have conduction abnormalities that may confound the QTc analysis.
• Have a personal or family history of long QT syndrome, family history of sudden death, personal history of unexplained syncope within the last year; or use prescription or over-the-counter medications known to prolong the QT or QTc interval.
• Have diastolic blood pressure (DBP) ≥95 millimeters of mercury (mm Hg) and/or systolic blood pressure (SBP) ≥160 mm Hg.
• Have an active or untreated malignancy or have been in remission from a clinically significant malignancy for <5 years.
• Have a history of a transplanted organ.
• Evidence of a significant active, uncontrolled endocrine or autoimmune abnormality, as judged by the investigator, at screening.
• Have a history of human immunodeficiency virus (HIV).
• Have a known allergy to yeast or yeast proteins, history of anaphylaxis with bronchospasm, or atopic dermatitis with chronic urticaria.
• Have any other condition (including known drug or alcohol abuse or psychiatric disorder within the last 6 months) that may preclude the participant from following and completing the protocol.
• Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (including pancreatitis), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
• Are women who are breastfeeding.
• Have had a significant change in weight, defined as a gain or loss of at least 4 kilograms (kg) (9 pounds) in the 90 days prior to randomization.
• Have taken in the 30 days prior to randomization, a medication, herbal product, or nutritional supplement that affects adipose mass or distribution or energy balance.
• Are receiving chronic (>2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received such therapy within 4 weeks immediately prior to second screening appointment.
• Have current or recent (within the past 3 months) use of gemfibrozil or fenofibrate, niacin, ezetimibe, or bile acid binding resins (for example, cholestyramines). Stable statin therapy of ≥3 months will be allowed.
• Are currently taking central nervous system (CNS) stimulant.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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47 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo-matching LY2405319 injected subcutaneously (SC) once daily for 28 days.

Treatment:

Drug: Placebo

3 mg LY2405319

Experimental group

Description:

Participants received 3 milligrams (mg) LY2405319 injected SC once daily for 28 days.

Treatment:

Drug: LY2405319

10 mg LY2405319

Experimental group

Description:

Participants received 10 mg LY2405319 injected SC once daily for 28 days.

Treatment:

Drug: LY2405319

20 mg LY2405319

Experimental group

Description:

Participants received 20 mg LY2405319 injected SC once daily for 28 days.

Treatment:

Drug: LY2405319