Clinical trial NCT02132637: A Study to Compare the Effect of a Double Dose of Two Long-acting Insulin Therapies in Participants With Type 2 Diabetes
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2014-05-07
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Clinically Significant Hypoglycemia
timeFrame: Predose to 84 Hours Post Double Dose
Secondary outcomes:
measure: Percentage of Participants With Clinically Significant Hypoglycemia 12 Hours Post Double Dose
timeFrame: Predose to 12 Hours Post Double Dose
measure: Percentage of Participants With Hypoglycemia
timeFrame: Predose to 12 Hours Post Double Dose and 84 Hours Post Double Dose
measure: Nadir Glucose
timeFrame: Predose to 84 Hours Post Double Dose
measure: Time to the Nadir Glucose
timeFrame: Predose to 84 Hours Post Double Dose
measure: Duration of Glucose ≤70 mg/dL
timeFrame: Predose to 84 Hours Post Double Dose
measure: Fasting Blood Glucose
timeFrame: Day 1, Day 2, and Day 3 Following Double Dose
measure: Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC)
timeFrame: Preprandial to 3 Hours Postprandial during the day following the standard dose
measure: Pharmacodynamics: Three-Hour Postprandial Glucose Area Under the Concentration Time Curve (AUC) Excursion
timeFrame: Preprandial to 3 Hours Postprandial during the day following the standard dose
measure: Beta Cell Function
timeFrame: 0-30 minutes during the meal tolerance test on the day following the standard dose
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research Inc
state: California
city: Mainz
country: Germany
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.
city: Neuss
country: Germany
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 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: