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

September 6, 2019 updated by: Eli Lilly and Company

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • 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
        • 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.
  • United States
    • California
      • Chula Vista, California, United States, 91911
        • Profil Institute For Clinical Research Inc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Predose to 84 Hours Post Double Dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Predose to 12 Hours Post Double Dose
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.
Predose to 12 Hours Post Double Dose and 84 Hours Post Double Dose
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.
Predose to 84 Hours Post Double Dose
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.
Predose to 84 Hours Post Double Dose
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.
Predose to 84 Hours Post Double Dose
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.
Day 1, Day 2, and Day 3 Following Double Dose
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.
Preprandial to 3 Hours Postprandial during the day following the standard dose
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.
Preprandial to 3 Hours Postprandial during the day following the standard dose
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.
0-30 minutes during the meal tolerance test on the day following the standard dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 5, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 7, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 18, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 6, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 14288
  • I2R-MC-BIDD (Other Identifier: Eli Lilly and Company)
  • 2012-005174-56 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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