Insulin Lispro 6 Days Versus Insulin Aspart 6 Days in Pump Use

• ClinicalTrials.gov Identifier: NCT01134107
• Recruitment Status: Completed
• First Posted: May 31, 2010
• Results First Posted: October 26, 2012
• Last Update Posted: April 11, 2013
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

Patients will continue to use their current insulin pump for this study. Patients will receive insulin lispro and insulin aspart during this study. One medication will be taken for 12 weeks and then the other medication for 12 weeks. Neither the patient nor the study doctor will know which medication is being taken at any time. The order in which the two medications are taken will be determined by chance.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 1	Drug: Insulin Lispro 6 Day (6D); Drug: Insulin Aspart 6 Day (6D)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Crossover Trial of CSII Reservoir In-use Comparing Insulin Lispro Formulation to Insulin Aspart in Patients With Type 1 Diabetes Mellitus
• Study Start Date: November 2010
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Insulin Lispro 6 Day (6D)	Drug: Insulin Lispro 6 Day (6D); Administered by infusion pump for 12 week treatment period; Other Names: Insulin Lispro Formulation; Humalog; LY275585
Active Comparator: Insulin Aspart 6 Day (6D)	Drug: Insulin Aspart 6 Day (6D); Administered by infusion pump for 12 week treatment period

Outcome Measures

Primary Outcome Measures :

1. Mean of Last Six 7-point Self Monitored Blood Glucose (SMBG) Taken on Day 6 for Insulin Lispro 6D and Insulin Aspart 6D Pump Reservoir In-use [ Time Frame: Day 6 of each reservoir cycle for the last 6 weeks of each 12-week treatment period (Week 7 through Week 12) ]

Secondary Outcome Measures :

1. Mean SMBG [ Time Frame: Days 1-6 and Day 2 and Day 6 for each reservoir cycle throughout each 12-week treatment period ]
   Mean SMBG for combined periods; all reported SMBG values on Days 1-6, Day 2, and Day 6 for Insulin Lispro 6D and Insulin Aspart 6D.
2. Mean Daily Insulin Dose (Total, Basal, and Bolus) [ Time Frame: Days 1-6 for each reservoir cycle throughout each 12-week treatment period ]
3. Change From Baseline to 12 Weeks for Each Treatment in Glycated Hemoglobin A1c (HbA1c) Values [ Time Frame: Baseline, endpoint for each 12-week treatment period ]
4. Number of Participants Who Achieve or Maintain a Glycated Hemoglobin A1c (HbA1c) Less Than or Equal to 6.5% and Less Than 7% [ Time Frame: Endpoint for each 12-week treatment period ]

Other Outcome Measures:

1. Change From Baseline to 12 Weeks for Daily Insulin Dose (Total, Basal, and Bolus) [ Time Frame: Baseline, endpoint for each 12-week treatment period ]
2. Percentage of Participants Having a Hyperglycemic Episode [ Time Frame: Days 1-6 for each reservoir cycle throughout each 12-week treatment period ]
   A hyperglycemic episode was defined as an event with (1) a measured blood glucose concentration >250 milligrams per deciliter (mg/dL) (13.9 millimoles per liter [mmol/L]) and ≥3 hours after eating, or (2) a measured blood glucose concentration >300 mg/dL (16.7 mmol/L) and <3 hours after eating
3. Hyperglycemic Episode Rate Per 30 Days [ Time Frame: Days 1-6 for each reservoir cycle throughout each 12-week treatment period ]
   Hyperglycemia was defined as an episode with (1) a measured blood glucose concentration >250 milligrams per deciliter [mg/dL] (13.9 millimoles per liter [mmol/L]) and ≥3 hours after eating, or (2) a measured blood glucose concentration >300 mg/dL (16.7 mmol/L) and <3 hours after eating. Rate is presented as the number of hyperglycemic episodes adjusted for 30 days.
4. Percentage of Participants With Pump Complications [ Time Frame: Days 1-6 for each reservoir cycle throughout each 12-week treatment period ]
   Overall pump complications are defined as any combination of the following, reported by the participant: tubing clogged, tubing kinked, tubing disconnect, tubing pulled out, blood in tubing, too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm, skin abscess at site, excessive redness at site, swelling (not nodule) at site, bleeding at site, bruising at site, reservoir change (infusion set change reason only), and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether the change occurred early (prior to 6 days). If he/she responded 'yes', then the reported change was recorded as a premature change.
5. Pump Complications Rate Per 30 Days [ Time Frame: Days 1-6 for each reservoir cycle throughout each 12-week treatment period ]
   Overall pump complications are defined as any combination of the following reported by the participant: tubing clogged, tubing kinked, tubing disconnect, tubing pulled out, blood in tubing, too much heat, too much cold, empty reservoir, low battery, occlusion alarm, no delivery alarm, skin abscess at site, excessive redness at site, swelling (not nodule) at site, bleeding at site, bruising at site, reservoir change (infusion set change reason only), and other. When either a reservoir change or an infusion set change was reported, participants were questioned whether the change occurred early (prior to 6 days). If he/she responded 'yes', then the reported change was recorded as a premature change.
6. Percentage of Participants Having a Hypoglycemic Episode [ Time Frame: All days for each reservoir cycle throughout each 12-week treatment period ]

   A Documented Hypoglycemic Episode is defined as an event which is associated with a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L).

   All Reported Hypoglycemic Episodes are defined as an event which is associated with

   1. reported signs and symptoms of hypoglycemia, and/or
   2. a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L)
7. Hypoglycemic Episode Rate Per 30 Days [ Time Frame: All days for each reservoir cycle throughout each 12-week treatment period ]

   All Reported Hypoglycemic Episodes are defined as an event which is associated with

   1. reported signs and symptoms of hypoglycemia, and/or
   2. a documented blood glucose (BG) concentration of <= 70 mg/dL (3.9 mmol/L)
8. Change From Baseline to 12 Week Endpoint for Each Treatment in Weight [ Time Frame: Baseline, endpoint for each 12-week treatment period ]
9. Change From Baseline to 12 Weeks Endpoint for Each Treatment in Blood Pressure [ Time Frame: Baseline, endpoint for each 12-week treatment period ]

Eligibility Criteria

• Ages Eligible for Study: 13 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosed with type 1 diabetes (World Health Organization criteria) for at least 24 months
• Treated with continuous subcutaneous insulin infusion (CSII) therapy for the previous 6 months
• Mean total daily insulin dose for 3 days prior to screening less than or equal to 46 units/day if using a 300-Unit reservoir, less than or equal to 30 units/day if using a 200 unit reservoir, or less than or equal to 26 units/day if using a 180 unit reservoir
• Baseline body mass index (BMI) less than or equal to 35.0 kilograms per meter squared (kg/m2)
• Baseline glycated hemoglobin A1c (HbA1c) 5% to 9%

Exclusion Criteria:

• Impaired renal function (serum creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL))
• Legal blindness
• Have had any episode in the 12 months prior to screening of hypoglycemic coma, seizures, or disorientation
• Have had hypoglycemia unawareness (routinely asymptomatic at blood glucose less than 45 mg/dL [2.5 millimoles per liter (mmol/L)]) in the 12 months prior to screening.
• Have had any emergency room visits or hospitalizations due to poor glucose control in the 12 months prior to screening.
• Have had a pump-related infusion site abscess in the 12 months prior to screening.
• Have had multiple, clinically significant occlusions as judged by the investigator.
• Have had any infection with Staphylococcus aureus in the past 5 years
• Have one of the following concomitant diseases: presence of clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease, or any other serious disease considered by the investigator to be exclusionary.
• Participants with malignancy other than basal cell or squamous cell skin cancer who have not yet been treated, are currently being treated, or who were diagnosed less than 5 years ago.
• Have had a blood transfusion or severe blood loss within the 3 months prior to screening or have known hemoglobinopathy, hemolytic or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with HbA1c methodology.
• Are receiving chronic systemic glucocorticoid therapy, or have received such therapy within the 4 weeks preceding screening.
• Have an irregular sleep/wake cycle in the investigator's opinion.
• Have a known hypersensitivity or allergy to any of the study insulins or their excipients
• 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.
• Are currently enrolled in, or discontinued within the last 30 days from a clinical trial involving off-label use of an investigational drug or device, or currently enrolled in any other type of medical research not to be scientifically or medically compatible with this study.
• Are unwilling or unable to comply with the use of a data collection device to directly record data from the participant.

Contacts and Locations

Locations

France

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.

Caen, France, 14033

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.

Corbeil-Essonnes, France, 91106

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.

La Rochelle, France, 17019

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.

Marseille, France, 13009

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.

Montpellier, France, 34295

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.

Narbonne, France, 11108

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.

Ludwigshafen, Germany, 67059

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.

Münster, Germany, 48145

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.

Neuwied, Germany, 56564

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.

Potsdam, Germany, 14469

Hungary

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.

Bekescsaba, Hungary, 5600

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.

Budapest, Hungary, 1023

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.

Nyiregyhaza, Hungary, 4400

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.

Zalaegerszeg, Hungary, 8900

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 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01134107
• Other Study ID Numbers: 12175; F3Z-MC-IOPW ( Other Identifier: Eli Lilly and Company )
• First Posted: May 31, 2010
• Results First Posted: October 26, 2012
• Last Update Posted: April 11, 2013
• Last Verified: April 2013

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Lispro; Hypoglycemic Agents; Physiological Effects of Drugs