Clinical trial NCT01869959: A Study of LY2405319 in Participants With Type 2 Diabetes
Official title: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2405319 With 28 Days of Subcutaneous Injections in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-06-05
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through Day 56
Secondary outcomes:
measure: Change From Baseline to Day 28 in Fasting Glucose
timeFrame: Baseline, Day 28
measure: 7 Point Self-monitored Blood Glucose (SMBG)
timeFrame: Baseline (Day -5, -4, or -3) and Week 4 (Days 24, 25, or 26)
measure: Change From Baseline to Week 4 in Glucose Area Under the Curve (AUC)
timeFrame: Predose and 2 hours postdose (Baseline, Week 4)
measure: Change From Baseline to Week 4 in Insulin Area Under the Curve (AUC)
timeFrame: Predose and 2 hours postdose (Baseline, Week 4)
measure: Change From Baseline to Week 4 in C-peptide Area Under the Curve (AUC)
timeFrame: Predose and 2 hours postdose (Baseline, Week 4)
measure: Change From Baseline to Day 28 in Fasting Lipid Profile
timeFrame: Baseline, Day 28
measure: Change From Baseline to Day 28 in Body Weight
timeFrame: Baseline, Day 28
measure: Change From Baseline to Day 28 in Adiponectin
timeFrame: Baseline, Day 28
measure: Change From Baseline to Day 28 in C-Reactive Protein
timeFrame: Baseline, Day 28
measure: Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2405319
timeFrame: Predose through Day 28 (48 hours postdose)
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY2405319
timeFrame: Predose through Day 28 (48 hours postdose)
measure: The Number of Participants With Anti-LY2405319 Antibodies
timeFrame: Day 1 through Day 56
measure: Change From Baseline to Day 28 in Eating Inventory for Cognitive Restraint of Eating, Disinhibition, and Hunger
timeFrame: Baseline, Day 28
measure: Change From Baseline to Day 28 in the Food Preference Questionnaire (FPQ) Score
timeFrame: Baseline, Day 28
measure: Change From Baseline to Day 28 in The Patient Health Questionnaire (PHQ-9) Score
timeFrame: Baseline, Day 28
Other outcomes:
Locations:
city: Cypress
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: California
city: Tustin
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: California
city: Deland
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Florida
city: Miramar
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Florida
city: Cincinnati
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Ohio
city: Portland
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Oregon
city: San Antonio
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: