Skip to main content
OpenTrials
Completed

NCT Number: NCT02132637

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

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

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Insulin Peglispro

Drug

Administered SQ

Other names: LY2605541

insulin glargine

Drug

Administered SQ

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study 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

Acronym: IMAGINE 8

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
May 7, 2014
Registry last updated
Sep 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.