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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01454284




Registration number
NCT01454284
Ethics application status
Date submitted
14/10/2011
Date registered
18/10/2011
Date last updated
17/04/2018

Titles & IDs
Public title
A Study in Participants With Type I Diabetes Mellitus
Scientific title
The Impact of LY2605541 Versus Insulin Glargine for Patients With Type 1 Diabetes Mellitus Treated With Preprandial Insulin Lispro: a Double-Blind, Randomized, 52-week Study
Secondary ID [1] 0 0
I2R-MC-BIAO
Secondary ID [2] 0 0
12147
Universal Trial Number (UTN)
Trial acronym
IMAGINE 3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: LY2605541 + Insulin Lispro - LY2605541 titrated based on blood glucose readings, administered subcutaneously (SC) once daily at bedtime for 52 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered SC at meal times for 52 weeks.

Active comparator: Glargine + Insulin Lispro - Glargine dose titrated based on blood glucose readings, administered SC once daily at bedtime for 52 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered SC at meal times for 52 weeks.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Hemoglobin A1c (HbA1c)
Timepoint [1] 0 0
52 weeks
Secondary outcome [1] 0 0
Hemoglobin A1c (HbA1c)
Timepoint [1] 0 0
26 weeks
Secondary outcome [2] 0 0
Change From Baseline to 52 Weeks in HbA1c
Timepoint [2] 0 0
Baseline, 52 weeks
Secondary outcome [3] 0 0
Total Hypoglycemia Events
Timepoint [3] 0 0
Baseline through 26 weeks, Baseline through 52 weeks
Secondary outcome [4] 0 0
Percentage of Participants With Total Hypoglycemic Events
Timepoint [4] 0 0
Baseline through 26 weeks, Baseline through 52 weeks
Secondary outcome [5] 0 0
Percentage of Participants With HbA1c Equal to or Less Than 6.5% and Less Than 7.0%
Timepoint [5] 0 0
up to 26 weeks, up to 52 weeks
Secondary outcome [6] 0 0
Percentage of Participants With HbA1c Less Than 7.0% and Without Nocturnal Hypoglycemia
Timepoint [6] 0 0
up to 26 weeks, up to 52 weeks
Secondary outcome [7] 0 0
Nocturnal Hypoglycemia Rates
Timepoint [7] 0 0
Baseline through 26 weeks, Baseline through 52 weeks
Secondary outcome [8] 0 0
Percentage of Participants With Nocturnal Hypoglycemic Events
Timepoint [8] 0 0
Baseline through 26 weeks, Baseline through 52 weeks
Secondary outcome [9] 0 0
Change in Body Weight
Timepoint [9] 0 0
Baseline, 26 weeks, 52 weeks
Secondary outcome [10] 0 0
9 Point Self-monitored Blood Glucose (SMBG)
Timepoint [10] 0 0
26 weeks and 52 weeks
Secondary outcome [11] 0 0
Fasting Serum Glucose (by Laboratory Measurement)
Timepoint [11] 0 0
26 weeks and 52 weeks
Secondary outcome [12] 0 0
Fasting Blood Glucose (by Participant Self Monitored Blood Glucose Readings)
Timepoint [12] 0 0
26 weeks and 52 weeks
Secondary outcome [13] 0 0
Intra-participant Variability of Fasting Blood Glucose (FBG)
Timepoint [13] 0 0
26 weeks and 52 weeks
Secondary outcome [14] 0 0
0300 Hours Blood Glucose (BG) to Fasting BG Excursion
Timepoint [14] 0 0
26 weeks and 52 weeks
Secondary outcome [15] 0 0
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
Timepoint [15] 0 0
26 weeks and 52 weeks
Secondary outcome [16] 0 0
Percentage of Participants With Change in Anti-LY2605541 Antibodies
Timepoint [16] 0 0
26 weeks, 52 weeks
Secondary outcome [17] 0 0
Basal, Meal Time, and Total Insulin Dose Per Body Weight
Timepoint [17] 0 0
26 weeks and 52 weeks
Secondary outcome [18] 0 0
Insulin Treatment Satisfaction Questionnaire
Timepoint [18] 0 0
up to 52 weeks
Secondary outcome [19] 0 0
European Quality of Life -5 Dimension (EQ-5D-3L)
Timepoint [19] 0 0
up to 52 weeks
Secondary outcome [20] 0 0
Adult Low Blood Sugar Survey
Timepoint [20] 0 0
26 weeks and 52 weeks
Secondary outcome [21] 0 0
Rapid Assessment of Physical Activity (RAPA)
Timepoint [21] 0 0
52 weeks

Eligibility
Key inclusion criteria
* Type 1 diabetes for at least 1 year
* HbA1c value less than 12 percent according to the central laboratory at screening
* Body mass index of less than or equal to 35.0 kilograms per square meter (kg/m^2)
* Have been treated for at least 90 days prior to screening with

* insulin detemir, insulin glargine, or Neutral Protamine Hagedorn (NPH) in combination with pre-meal insulin, or
* self-mixed or pre-mixed insulin regimens with any basal and bolus insulin combination administered at least twice daily, or
* continuous SC insulin infusion therapy
* Women who are not breast feeding and test negative for pregnancy before receiving treatment and agree to use reliable birth control until 2 weeks after last treatment with study drug
* Are capable and willing to adhere to multiple daily injections, inject with a vial and syringe and prefilled pen and perform self-monitored blood glucose (SMBG) readings and record keeping
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Are using twice daily insulin glargine having been inadequately controlled on single daily dose of glargine prior to screening
* Excessive insulin resistance defined as having received a total daily dose of insulin greater than 1.5 units per kilogram (U/kg) at the time of randomization
* Receiving any oral or injectable medication (other than insulins or metformin for treatment of polycystic ovarian disease) intended for the treatment of diabetes mellitus in the 90 days prior to screening
* Lipid lowering medications:

* are using niacin preparations as lipid lowering medication and/or bile acid sequestrants within 90 days prior to screening; or,
* are using lipid lowering medication at a dose that has not been stable for 90 days or more prior to screening
* Have fasting hypertriglyceridemia (defined as greater than 4.5 millimoles per liter [mmol/L], greater than 400 milligrams per deciliter [mg/dL]) at screening, as determined by the central laboratory.
* Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within 6 months prior to screening
* Have had 2 or more emergency room visits or hospitalizations due to poor glucose control within 6 months prior to screening
* Have cardiac disease with functional status that is New York Heart Association Class III or IV
* Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than 2.5 mg/dL
* Have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non-alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements as indicated below:

* total bilirubin 2 times or more than the upper limit of normal (ULN) as defined by the central laboratory, or
* alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT) more than 2.5 times ULN as defined by the central laboratory, or
* aspartate aminotransferase (AST)/(serum glutamic oxaloacetic transaminase (SGOT) more than 2.5 times ULN as defined by the central laboratory
* Have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or are at increased risk for developing cancer or a recurrence of cancer
* Diagnosed clinically significant diabetic autonomic neuropathy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2014
Sample size
Target
Accrual to date
Final
1114
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
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. - Merewether
Recruitment hospital [2] 0 0
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. - Keswick
Recruitment hospital [3] 0 0
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. - Box Hill
Recruitment hospital [4] 0 0
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. - Parkville
Recruitment postcode(s) [1] 0 0
2291 - Merewether
Recruitment postcode(s) [2] 0 0
5035 - Keswick
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
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Huddinge
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Karlstad
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Avon
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Hampshire
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Scotland
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Suffolk
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Northampton
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Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is:

* To compare blood sugar control on LY2605541 with insulin glargine after 52 weeks of treatment.
* To compare the rate of nocturnal low blood sugar episodes on LY2605541 with insulin glargine during 52 weeks of treatment.
* To compare the number of participants on LY2605541 reaching blood sugar targets without low blood sugar episodes at night to those taking insulin glargine after 52 weeks of treatment.
* To compare the rate of low blood sugar episodes on LY2605541 with insulin glargine during 52 weeks of treatment
Trial website
https://clinicaltrials.gov/study/NCT01454284
Trial related presentations / publications
Sanyal A, Cusi K, Hartman ML, Zhang S, Bastyr EJ 3rd, Bue-Valleskey JM, Chang AM, Haupt A, Jacober SJ, Konrad RJ, Zhang Q, Hoogwerf BJ. Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes and effects of two different insulins. J Investig Med. 2018 Mar;66(3):661-668. doi: 10.1136/jim-2017-000609. Epub 2017 Nov 21.
Orchard TJ, Cariou B, Connelly MA, Otvos JD, Zhang S, Antalis CJ, Ivanyi T, Hoogwerf BJ. The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes. Cardiovasc Diabetol. 2017 Jun 6;16(1):73. doi: 10.1186/s12933-017-0555-1.
Cusi K, Sanyal AJ, Zhang S, Hartman ML, Bue-Valleskey JM, Hoogwerf BJ, Haupt A. Non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes. Diabetes Obes Metab. 2017 Nov;19(11):1630-1634. doi: 10.1111/dom.12973. Epub 2017 Jun 22.
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01454284