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A Study to Compare the Effect of a Double Dose of Two Long-acting Insulin Therapies in Participants With Type 2 Diabetes (IMAGINE 8)

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ClinicalTrials.gov Identifier: NCT02132637
Recruitment Status : Completed
First Posted : May 7, 2014
Results First Posted : April 20, 2018
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The primary purpose of this study is to compare the effect of a double dose of a study drug known as insulin peglispro to a double dose of insulin glargine in participants who have type 2 diabetes. Participants will be treated with study insulin daily, in two 4-week study periods. Each participant will receive insulin peglispro during one treatment period and insulin glargine during the other treatment period.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Insulin Peglispro Drug: Insulin Glargine Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Comparison of Pharmacodynamics When Receiving a Double Dose of Insulin Peglispro or Insulin Glargine in Patients With Type 2 Diabetes Mellitus: A Double-Blind, Crossover Design Study
Study Start Date : May 2014
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Insulin Peglispro
Standard dose of insulin peglispro administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin peglispro administered once, SQ on day 3 of the inpatient stay.
Drug: Insulin Peglispro
Administered SQ
Other Name: LY2605541
Experimental: Insulin Glargine
Standard dose of insulin glargine administered subcutaneously (SQ) once daily for 4 weeks in one of two study periods. Double dose of insulin glargine administered once, SQ on day 3 of the inpatient stay.
Drug: Insulin Glargine
Administered SQ



Primary Outcome Measures :
  1. Percentage of Participants With Clinically Significant Hypoglycemia [ Time Frame: Predose to 84 Hours Post Double Dose ]
    The percentage was calculated by dividing the number of participants with clinically significant hypoglycemia events defined as blood glucose <54 milligrams per deciliter (mg/dL) (3.0 millimole per liter [mmol/L]) or symptoms of severe hypoglycemia by the total number of participants analyzed, multiplied by 100.


Secondary Outcome Measures :
  1. Percentage of Participants With Clinically Significant Hypoglycemia 12 Hours Post Double Dose [ Time Frame: Predose to 12 Hours Post Double Dose ]
    The percentage was calculated by dividing the number of participants with clinically significant hypoglycemia events defined as blood glucose <54 mg/dL (3.0 mmol/L) or symptoms of severe hypoglycemia by the total number of participants analyzed, multiplied by 100.

  2. Percentage of Participants With Hypoglycemia [ Time Frame: Predose to 12 Hours Post Double Dose and 84 Hours Post Double Dose ]
    The percentage was calculated by dividing the number of participants with hypoglycemia events defined as blood glucose ≤70 mg/dL (3.9 mmol/L) by the total number of participants analyzed, multiplied by 100.

  3. Nadir Glucose [ Time Frame: Predose to 84 Hours Post Double Dose ]
    Nadir glucose was defined as the lowest blood glucose for a participant with blood glucose ≤70 mg/dL (3.9 mmol/L). Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

  4. Time to the Nadir Glucose [ Time Frame: Predose to 84 Hours Post Double Dose ]
    Nadir glucose was defined as the lowest blood glucose for a participant with blood glucose ≤70 mg/dL (3.9 mmol/L). The average time was calculated by dividing the sum of time from double dose to the nadir glucose for participants with blood glucose ≤70 mg/dL (3.9 mmol/L) by the number of participants with blood glucose ≤70 mg/dL (3.9 mmol/L) during the first 84 hours after the double dose.

  5. Duration of Glucose ≤70 mg/dL [ Time Frame: Predose to 84 Hours Post Double Dose ]
    The duration in minutes of each hypoglycemia episode with glucose ≤70 mg/dL (3.9 mmol/L) was calculated from start time to end time. The duration for a participant was the sum of the durations over the multiple hypoglycemia episodes. LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

  6. Fasting Blood Glucose [ Time Frame: Day 1, Day 2, and Day 3 Following Double Dose ]
    Fasting blood glucose (FBG) was measured by self-monitored blood glucose. LS means were calculated by MMRM analysis with fixed effects of treatment, dosing day, sequence, period, interaction of treatment and dosing day, baseline basal insulin dose stratification factor, and baseline FBG.

  7. Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) [ Time Frame: Preprandial to 3 Hours Postprandial during the day following the standard dose ]
    Glucose AUC within 3 hours after each meal assessed by the AUC of glucose from preprandial to 3 hours postprandial. LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

  8. Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Excursion [ Time Frame: Preprandial to 3 Hours Postprandial during the day following the standard dose ]
    Glucose AUC excursion within 3 hours after each meal assessed by the AUC of adjusted glucose (= observed glucose - preprandial glucose) from preprandial to 3 hours postprandial. LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.

  9. Beta Cell Function [ Time Frame: 0-30 minutes during the meal tolerance test on the day following the standard dose ]
    Beta cell function assessed by the change between pre meal tolerance test and 30 minutes post meal tolerance test in C-peptide corrected insulin/Glucose (ΔC-peptide corrected insulin/ΔGlucose). LS means were calculated using an MMRM analysis including the following fixed effects: treatment, period, sequence, and baseline basal insulin dose stratification factor.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have type 2 diabetes mellitus (T2DM), based on the World Health Organization (WHO) classification, for ≥1 year.
  • Use any type of basal insulin (except degludec), including once-or twice-daily human insulin neutral protamine Hagedom (NPH), insulin detemir, or insulin glargine.
  • Have hemoglobin A1c (HbA1c) levels ≤9.0% according to local laboratory testing at screening.
  • Have body mass index (BMI) ≤40.0 kilograms/square meter (kg/m^2).
  • Have been treated with stable doses of insulin for at least 30 days before screening with:

    • Basal insulin with daily doses ±30% of mean during the last 4 weeks.
    • Doses of a basal insulin must be between 0.3 unit/kg/day and 1 unit/kg/day.
  • If on metformin, thiazolidinediones (TZDs), sodium glucose co-transporter 2 (SGLT-2) inhibitors, or dipeptidyl peptidase (DPP4) inhibitors, must be on stable doses for the last 30 days.

Exclusion Criteria:

  • Are using prandial, self-mixed, or premixed insulin. Participants using prandial insulin may be switched to everyday (qd) glargine if investigator judges that the participant will still meet fasting glucose requirements for randomization.
  • Are using insulin pump therapy.
  • Have excessive insulin resistance: Defined as >1.0 unit/kg/day as baseline treatment.
  • If being treated with sulfonylureas (SUs) before screening, then must have SUs washed out between screening and randomization.
  • Use any of these concomitant medications: morphine, codeine, antidiuretics, glucagon-like peptide-1 (GLP-1) receptor agonists (for example, exenatide, exenatide once weekly, lixisenatide or liraglutide), or pramlintide, used concurrently or within 90 days before screening.
  • Have hypoglycemia unawareness, defined as confirmed by laboratory test results or by historical episodes of hypoglycemia <54 mg/dL (3.0 mmol/L) without symptoms.
  • Have fasting hypertriglyceridemia >400 mg/dL (>4.5 mmol/L) at screening, as determined by the local laboratory.
  • Have had any episode of severe hypoglycemia (defined by requiring assistance due to neurologically disabling hypoglycemia) within 6 months before entry into the study.
  • Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months.
  • Have had a previous clinically significant episode of ketoacidosis as determined by the investigator (ketone bodies at fasting and without acidosis is acceptable) in the past 6 months.
  • Have history of renal transplantation, are currently receiving renal dialysis, or have estimated Glomerular Filtration Rate (eGFR) <60 milliliters/minute.
  • Have obvious clinical signs or symptoms of liver disease (excluding nonalcoholic fatty liver disease), acute or chronic hepatitis, nonalcoholic steatohepatitis, or elevated liver enzyme measurements.
  • 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 in the opinion of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02132637


Locations
United States, California
Profil Institute for Clinical Research Inc
Chula Vista, California, United States, 91911
Germany
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.
Mainz, Germany, 55116
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.
Neuss, Germany, 41460
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02132637     History of Changes
Other Study ID Numbers: 14288
I2R-MC-BIDD ( Other Identifier: Eli Lilly and Company )
2012-005174-56 ( EudraCT Number )
First Posted: May 7, 2014    Key Record Dates
Results First Posted: April 20, 2018
Last Update Posted: April 20, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.


Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs