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Completed

NCT Number: NCT01774968

Study of Human Regular U-500 Insulin in Adult Participants With Type 2 Diabetes

The main purpose of this study is to compare the effectiveness of Human Regular U-500 Insulin three times a day versus twice a day.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

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., Bayamón, Puerto Rico

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Who can participate

Healthy volunteers accepted: No

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

Major Inclusion Criteria:

  • Have type 2 diabetes mellitus (World Health Organization [WHO] Classification of Diabetes)
  • Have a body mass index (BMI) ≥25 kilogram per square meter (kg/m^2)
  • Have Glycated Hemoglobin A1c (HbA1c) ≥7.5% and ≤12.0%, as measured by the central laboratory at entry
  • Current U-100 insulin/analogue users on >200 and ≤600 units per day for ≥3 months at study entry and reconfirmed at randomization
  • Have a history of stable body weight for at least 3 months prior to study entry
  • Concomitant medications may include metformin (MET), dipeptidyl peptidase-4 (DPP-4) inhibitors approved for use with insulin at time of study entry (for example, sitagliptin, saxagliptin, and linagliptin), pioglitazone, and/or sulfonylureas (SUs)/glinides (repaglinide or nateglinide). Participant's oral antihyperglycemic drug (OAD) dose(s) must have been stable for ≥3 months

Major Exclusion Criteria:

  • Have type 1 diabetes mellitus or other types of diabetes mellitus apart from type 2 diabetes mellitus
  • Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase or aspartate aminotransferase levels ≥3 times the upper limit of the reference range
  • Have chronic kidney disease stage 4 and higher or history of renal transplantation
  • Have history of more than 1 episode of severe hypoglycemia within the 6 months prior to study entry
  • Have received insulin by continuous subcutaneous insulin infusion in the 3 months prior to study entry
  • Have received U-500R in the 3 months prior to study entry
  • Have had a blood transfusion or severe blood loss within 3 months prior to study entry or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia
  • Are taking chronic systemic glucocorticoid therapy or have received such therapy within the 4 weeks immediately prior to study entry
  • Have an irregular sleep/wake cycle
  • Have used rosiglitazone, once- or twice-daily glucagon-like peptide-1 (GLP-1) receptor agents, pramlintide, or other injectable or oral antihyperglycemic therapy not listed in the inclusion criteria in the 3 months prior to study entry. Participants may not have used once-weekly GLP-1 receptor agents in the 4 months prior to study entry
  • Have used any weight loss drugs in the 3 months prior to study entry
  • Have a history of bariatric surgery
  • Have a history of malignancy other than basal cell or squamous cell skin cancer
  • Have New York Heart Association (NYHA) Class III or IV per NYHA Cardiac Disease Functional Classification
  • Are breastfeeding or pregnant, or intend to become pregnant during the course of the study, or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable

Treatment and study plan

Human Regular U-500 Insulin

Drug

Other names: LY041001, Humulin R, U-500R

Primary outcomes

  1. Change From Baseline to Week 24 in Glycated Hemoglobin A1c (HbA1c)

    Time frame: Baseline, Week 24

    Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with investigator, baseline total daily dose (TDD; ≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.

Secondary outcomes

  1. Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24

    Time frame: Week 24

    The percentage of participants achieving an HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100.

  2. 30-Day Adjusted Rate of Hypoglycemic Events

    Time frame: Baseline through Week 24

    Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person [accompanied by neurologic/cognitive impairment]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose [PG] ≤70 milligrams per deciliter [mg/dL]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  3. Change From Baseline to Week 24 in Body Weight

    Time frame: Baseline, Week 24

    LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.

  4. Change From Baseline to Week 24 in Total Daily Dose (TDD; Units) of Insulin

    Time frame: Baseline, Week 24

    Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate.

  5. Change From Baseline to Week 24 in Total Daily Dose (TDD; Units/kg) of Insulin

    Time frame: Baseline, Week 24

    Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate.

  6. Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) Levels

    Time frame: Baseline, Week 24

    LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline FPG as a covariate.

  7. Time to Reach HbA1c Target Values

    Time frame: Baseline through 6, 12, 18, and 24 weeks.

    The cumulative number of participants achieving an HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% is summarized at Weeks 6, 12, 18, and 24. The number of participants at risk (n) is also provided for each target value and timepoint.

  8. Percentage of Participants With Hypoglycemic Events

    Time frame: Baseline through Week 24

    Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person [accompanied by neurologic/cognitive impairment]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose [PG] ≤70 milligrams per deciliter [mg/dL]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The percentage of participants with HE at 24 weeks was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  9. Change From Baseline to Week 24 in Number of Insulin Injections

    Time frame: Baseline, Week 24

    The number of insulin injections per day at baseline (Week 0) and at Week 24 are presented.

  10. Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)

    Time frame: Baseline, Week 24

    The 7-point SMBG is a participant self-administered blood glucose test which utilizes measurements at specific time points over a 24-hour period, including pre-morning meal (fasting), 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and 3 AM. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline SMBG as a covariate.

  11. Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg

    Time frame: Baseline, Week 24

    Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or >2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.

  12. Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg

    Time frame: Baseline, Week 24

    Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or >2.0 units/kg). Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person [accompanied by neurologic/cognitive impairment]), documented symptomatic (DS; an event which is associated with signs/symptoms of hypoglycemia and plasma glucose [PG] ≤70 milligrams per deciliter [mg/dL]), or nocturnal (Noc; any documented symptomatic HE that occurred between bedtime and waking). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

  13. Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg

    Time frame: Baseline, Week 24

    Participants were stratified by their baseline TDD insulin (≤2.0 units (U)/kg or >2.0 U/kg). The percentage of participants at risk of developing hypoglycemia (including documented symptomatic, asymptomatic, probable symptomatic, unspecified, or severe hypoglycemia) is presented at Baseline and at Week 24 and was calculated using MMRM fit with options of the binomial distribution and log link function including treatment, TDD (>300 units or ≤300 units), pioglitazone use (yes or no), visit, and treatment-by-visit interaction as fixed effects, and baseline HbA1c value as a covariate.

  14. Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg

    Time frame: Baseline, Week 24

    Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or >2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

Two Treatment Approaches for Human Regular U-500 Insulin (Thrice-Daily Versus Twice-Daily) in Subjects With Type 2 Diabetes Mellitus Not Achieving Adequate Glycemic Control on High-Dose U-100 Insulin Therapy With or Without Oral Agents: A Randomized, Open-Label, Parallel Clinical Trial

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Jan 24, 2013
Registry last updated
Sep 22, 2015

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.

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