Clinical trial NCT01792284: A Study of LY2605541 in Participants With Type 1 Diabetes Mellitus
Official title: A Comparison of LY2605541 Once Daily at a Fixed Time With LY2605541 Variable Time of Dosing in Participants With Type 1 Diabetes Mellitus: An Open Label, Randomized, Crossover Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-02-15
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary purpose of participation in this study is to compare the safety and efficacy of different dosing schedules of LY2605541 and how different dosing schedules of LY2605541 affect Hemoglobin A1c (HbA1c). Participants will be treated for up to 36 weeks with LY2605541 (one 12-week Lead-in period and two 12-week Randomization periods) and will participate in a total of 42 weeks of total study enrollment, including a 2-week Screening period and a 4-week Follow-up period.

Detailed description: This study involved a comparison of LY2605541 regimens, each administered with bolus insulin lispro. Eligible participants were switched to a fixed evening LY2605541dosing regimen at the beginning of the 12-week lead-in period. LY2605541 was administered SQ once-daily using a prefilled insulin device. The LY2605541dose was adjusted using a dosing algorithm adapted from Bartley and Bolli (Bartley et al. 2008, Bolli et al. 2009) based on the participant's blood glucose (BG) values and documented hypoglycemia during the previous week. Participants not already receiving insulin lispro for prandial dosing were switched to insulin lispro at the beginning of the 12-week lead-in period. Adjustments to insulin lispro doses were based on the insulin dosing algorithms adapted from Riddle and Bergenstal (Riddle et al. 2003, Bergenstal et al. 2008). At the time of randomization, participants were randomized to begin either the fixed evening dosing regimen or the variable time dosing regimen. Each participant was crossed over to the alternate regimen after 12 weeks. The insulin device (prefilled pen) remained the same throughout the study.

Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes mellitus for at least 1 year
* Have an HbA1c value \<9.0%
* Have a body mass index (BMI) ≤35.0 kilogram per square meter (kg/m\^2)
* Currently using basal/ bolus insulin
* Women of childbearing potential are not breastfeeding and must use methods to prevent pregnancy

Exclusion Criteria:

* Have excessive insulin resistance
* Are taking medications other than insulin for diabetes
* High triglycerides
* Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia as determined by the investigator) within 6 months prior to entry into the study
* Have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemia or diabetic ketoacidosis) in the past 6 months
* Have cardiac disease with functional status that is New York Heart Association (NYHA) Class III or IV (per NYHA Cardiac Disease Classification)
* Have impaired renal function
* Have impaired liver function
* Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with HbA1c measurement
* Have cancer, recent cancer, or risk of cancer
* Have a known hypersensitivity or allergy to any of the study insulins or their excipients
* Have chronic systemic glucocorticoid users
* Have clinically significant diabetic autonomic neuropathy
* Have irregular sleep/wake cycle
* Have been treated with a drug within the last 30 days that has not received regulatory approval at the time of study entry
* Prior study participation
* Are using or have used niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening

Primary outcomes:
measure: Hemoglobin A1c (HbA1c) at 12 Weeks
timeFrame: At 12 Week in Each Randomization Period
Secondary outcomes:
measure: 30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events
timeFrame: Baseline (Day 1) of Randomization Period through 24 Weeks (12 weeks in each Randomization Period)
measure: Percentage of Participants With Total and Nocturnal Hypoglycemic Events
timeFrame: Baseline (Day 1) of Randomization Period through 24 weeks (12 weeks in each Randomization Period)
measure: Fasting Blood Glucose (FBG) Measured by Self-Monitored Blood Glucose
timeFrame: At 12 Weeks in Each Randomization Period
measure: Intra-Participant Variability of FBG at 12 Weeks
timeFrame: At 12 Weeks in Each Randomization Period
measure: Fasting Serum Glucose (FSG) at 12 Weeks
timeFrame: At 12 Weeks in Each Randomization Period
measure: Change From Randomization to 12 Weeks in 9-Point SMBG
timeFrame: Randomization, 12 Weeks in Each Randomization Period
measure: Self-Monitored Blood Glucose (SMBG) at 12 Weeks
timeFrame: At 12 Week in Each Randomization Period
measure: Intra-participant Variability in SMBG at 12 Weeks
timeFrame: At 12 Week in Each Randomization Period
measure: Change From Randomization to 12 Weeks in Body Weight
timeFrame: Randomization, 12 Weeks in Each Randomization Period
measure: Change From Day 1 of Lead-In Period to 36 Weeks in Body Weight
timeFrame: Day 1 of Lead-In Period, 36 Weeks
measure: Change From Randomization to 12 Weeks in HbA1c
timeFrame: Randomization, 12 Weeks in Each Randomization Period
measure: Participants With Treatment-Emergent Anti-LY2605541 Antibody Response
timeFrame: Day 1 of Lead-in Period through 36 Weeks
measure: Basal, Bolus, and Total Insulin Doses at 12 Weeks
timeFrame: At 12 Weeks in Each Randomization Period
measure: Proportion of Bolus to Total Insulin Doses at 12 Weeks
timeFrame: At 12 Weeks in Each Randomization Period
measure: 0300-Hour Blood Glucose to Fasting Blood Glucose Excursion
timeFrame: At 12 Week in Each Randomization Period
measure: Change From Day 1 of Lead-in to 36 Weeks in Triglycerides, Total Cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C)
timeFrame: Day 1 of Lead-In Period, 36 Weeks
measure: Percentage of Participants With HbA1c <7.0% and ≤6.5% at 12 Weeks
timeFrame: At 12 Weeks in Each Randomization Period
Other outcomes:
Locations:
city: Concord
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: Escondido
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: Fresno
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: Aurora
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: Colorado
city: Roswell
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: Georgia
city: Idaho Falls
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: Idaho
city: Crystal Lake
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: Illinois
city: Des Moines
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: Iowa
city: Topeka
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: Kansas
city: Lexington
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: Kentucky
city: Oklahoma City
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: Oklahoma
city: Greer
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: South Carolina
city: Chattanooga
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: Tennessee
city: Austin
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
city: Dallas
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
city: Round Rock
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
city: Bayamon
country: Puerto Rico
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.
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: