Comparison of Two Basal Insulin Therapies for Patients With Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

— IOOZ  

Official title:

Comparison of Two Basal Insulin Analogs (Insulin Lispro Protamine Suspension and Insulin Detemir) in Basal-Bolus Therapy for Patients With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00487240
• Other study ID #: 10937
• Secondary ID: F3Z-MC-IOOZ
• Status: Completed
• Phase: Phase 3
• First received: June 14, 2007
• Last updated: October 20, 2010
• Start date: June 2007
• Est. completion date: August 2008

Study information

• Verified date: October 2010
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the efficacy and safety of insulin lispro protamine suspension (ILPS) as compared to insulin detemir as basal insulin combined with mealtime insulin therapy in patients with type 1 diabetes. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.

Description:

Phase 3b, randomized, multicenter, multinational, open-label, two-arm, active control, parallel study to determine safety, efficacy, and noninferiority of basal analog insulin lispro protamine suspension (ILPS, also referred to as NPL [neutral protamine Hagedorn]), injected two times a day, compared with basal analog insulin detemir, injected two times a day, as measured by change in hemoglobin A1c (HbA1c) from baseline (Visit 2) to 32 weeks in adult patients with type 1 diabetes when used in combination with bolus insulin lispro, injected three times a day.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 387
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis of type 1 diabetes for one year or more

• Age 18 years or older

• Body mass index (BMI) less than or equal to 35 kilograms per square meter (kg/m2)

• Have a hemoglobin A1c (HbA1c) 1.2 to 2.0 times the upper limit of the normal (ULN) reference range within 30 days prior to Visit 1 or collected and analyzed at a local laboratory at Visit 1

• As determined by the investigator, are capable and willing to do the following:

• perform self monitoring of blood glucose (SMBG),

• complete patient diaries as required for this protocol,

• use the insulin injection device(s) according to the instructions provided,

• are receptive to diabetes education,

• comply with the required study visits.

Exclusion Criteria:

• Have taken any oral antihyperglycemic medications (OAMs) within 3 months prior to Visit 1.

• Have had more than one episode of severe hypoglycemia, as defined in the Abbreviations and Definitions section of the protocol, within 6 months prior to entry into the study

• Are 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 or women who are breastfeeding

• Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, intraocular, and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding Visit 1.

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1

Intervention

Drug:
• Insulin Lispro Protamine Suspension
Patient specific dose, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks.
• Insulin Levemir
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks

Locations

Country	Name	City	State
Argentina	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.	Buenos Aires
Argentina	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 Plata
Australia	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.	Box Hill	Victoria
Australia	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.	Wollongong	New South Wales
Brazil	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.	Fortaleza
Brazil	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.	São Paulo
Greece	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.	Athens
Greece	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.	Thessaloniki
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.	Budapest
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.	Mosonmagyarovar
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.	Pecs
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.	Szentes
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.	Zalaegerszeg
Mexico	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.	Guadalajara
Mexico	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.	Pachuca
Mexico	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.	Puebla
Romania	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.	Baia Mare
Romania	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.	Brasov
Romania	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.	Bucharest
Romania	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.	Iasi
Russian Federation	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.	Arkhangelsk
Russian Federation	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.	Moscow
Russian Federation	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.	Rostov-On-Don
Russian Federation	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.	Saint Petersburg
United States	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.	Idaho Falls	Idaho
United States	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.	San Antonio	Texas
United States	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.	Springfield	Illinois
United States	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.	Topeka	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Greece,  Hungary,  Mexico,  Romania,  Russian Federation, 

References & Publications (1)

Chacra AR, Kipnes M, Ilag LL, Sarwat S, Giaconia J, Chan J; COMPLETE T1D investigators. Comparison of insulin lispro protamine suspension and insulin detemir in basal-bolus therapy in patients with Type 1 diabetes. Diabet Med. 2010 May;27(5):563-9. doi: 1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint		baseline and 32 weeks	No
Secondary	Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values	The summary statistics represents the mean of all subjects. Change from baseline is calculated for each individual subject for the specific visit and then the "mean change from baseline" is calculated by averaging out for all subjects. [Sum over all (i) {A1c at Week 8 for Subject(i) minus A1c Baseline for Subject (i)}/Total Subjects]. Therefore, for example, the Change from Baseline is not equal to the difference of Mean A1c for Week 8 minus Mean A1c for baseline.	Baseline, 8,16, 24, 32 Weeks	No
Secondary	Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%		32 Weeks	No
Secondary	7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint	Actual daily mean blood glucose levels at endpoint. The SMBG excursion is the difference between the postprandial and preprandial blood glucose concentration taken at the morning, midday and evening meals.	32 Weeks	No
Secondary	Glycemic Variability at Endpoint	Glycemic variability was measured by standard deviation (SD) value of fasting blood glucose as measured by intra-patient glycemic variability (determined by the 7-point self-monitored blood glucose [SMBG] profiles at endpoint); mean value (M-value), which was the mean of the intra-days self-monitored blood glucose values, and by the mean of daily difference (MODD), which was the mean of the between-days self-monitored blood glucose values.	32 Weeks	No
Secondary	Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint	Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of <2.8 mmol/L (<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.	Baseline to 32 Weeks	Yes
Secondary	1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint	Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of <2.8 mmol/L (<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.	baseline to 32 weeks	Yes
Secondary	30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint		baseline to 32 weeks	No
Secondary	Change From Baseline in Absolute Body Weight at 32 Week Endpoint		Baseline, 32 Weeks	No
Secondary	Insulin Dose Per Body Weight (Total and By Component [Basal and Bolus])	Total daily insulin dose adjusted for body weight (U/kg/day) was assessed.	32 Weeks	No
Secondary	Insulin Dose (Total and By Component [Basal and Bolus])	Total daily insulin dose (U/day) was assessed.	32 weeks	No

External Links

•   Lilly Clinical Trial Registry