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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01027871




Trial ID
NCT01027871
Ethics application status
Date submitted
8/12/2009
Date registered
8/12/2009
Date last updated
4/05/2018

Titles & IDs
Public title
A Study for Patients With Type 2 Diabetes
Scientific title
A Phase 2 Study of LY2605541 Compared With Insulin Glargine in the Treatment of Type 2 Diabetes Mellitus
Secondary ID [1] 0 0
I2R-MC-BIAC
Secondary ID [2] 0 0
12149
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY2605541
Treatment: Drugs - insulin glargine

Experimental: LY2605541 Dosing Algorithm 1 - Participants took both LY2605541 and their pre-study insulin for first several days

Experimental: LY2605541 Dosing Algorithm 2 - Participants took only LY2605541 with first dose doubled

Active Comparator: Insulin glargine -


Treatment: Drugs: LY2605541
subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks

Treatment: Drugs: insulin glargine
subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles - 8-point SMBG profiles are measured at morning FBG, midday and evening pre-meal blood glucose (BG), 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. Least squares (LS) mean of the FBG is from mixed-model repeated measures (MMRM) approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-interim analysis [IA], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline hemoglobin A1c [HbA1c] group); visit; visit and treatment interaction; random effect for participant.
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and random effect for participant.
Timepoint [1] 0 0
Baseline, Week 12
Secondary outcome [2] 0 0
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint - HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 dose algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.
Timepoint [2] 0 0
Baseline, Week 12
Secondary outcome [3] 0 0
Percentage of Participants With HbA1c <7.0% and =6.5% at Week 12 Endpoint - HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Percentage of Participants With HbA1c <7.0% and HbA1c =6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment - HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of =3.9 millimole/Liter (mmol/L) (=70 milligram/deciliter [mg/dL]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - 8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Daily Basal Insulin Dose at Week 2 and Week 12 - LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Timepoint [6] 0 0
Week 2 and Week 12
Secondary outcome [7] 0 0
Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of =3.9 mmol/L (=70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Timepoint [7] 0 0
Baseline through Week 12
Secondary outcome [8] 0 0
Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of =3.9 mmol/L (=70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk*30.
Timepoint [8] 0 0
Baseline through Week 12
Secondary outcome [9] 0 0
Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 - Negative is defined as either 'negative' from lab or percent binding <1.16%. Positive is defined as the percent binding is =1.16%. The antibody status change is from negative to positive or positive to negative.
Timepoint [9] 0 0
Week 12 and Week 16
Secondary outcome [10] 0 0
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Timepoint [10] 0 0
Baseline and Week12
Secondary outcome [11] 0 0
Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 12 Endpoint - The drug (LY2605541) concentration at steady state (Css) is calculated from the clearance (Liter/hour) and the final dose of the participants. Clearance was estimated using population-based approaches.
Timepoint [11] 0 0
Week 12
Secondary outcome [12] 0 0
Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms - FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Timepoint [12] 0 0
Baseline, Week 12
Secondary outcome [13] 0 0
Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms - HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.
Timepoint [13] 0 0
Baseline, Week 12
Secondary outcome [14] 0 0
Percentage of Participants With HbA1c <7.0% and =6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms - HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Timepoint [14] 0 0
Week 12
Secondary outcome [15] 0 0
Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c =6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms - HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of =3.9 mmol/L (=70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Timepoint [15] 0 0
Week 12
Secondary outcome [16] 0 0
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms - 8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Timepoint [16] 0 0
Week 12
Secondary outcome [17] 0 0
Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms - LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Timepoint [17] 0 0
Week 2 and Week 12
Secondary outcome [18] 0 0
Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms - Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of =3.9 mmol/L (=70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Timepoint [18] 0 0
Baseline through Week 12
Secondary outcome [19] 0 0
Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms - Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of =3.9 mmol/L (=70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk*30.
Timepoint [19] 0 0
Baseline through Week 12
Secondary outcome [20] 0 0
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms - Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant.
Timepoint [20] 0 0
Baseline and Week 12

Eligibility
Key inclusion criteria
- Type 2 diabetes mellitus (T2DM) for at least 1 year

- At least 18 years of age

- Using metformin and/or sulfonylurea(s) with once daily glargine or NPH for at least 3
months prior to the study. Prestudy dose requirements: insulin dose maximum 1.0
unit/kilogram/day (U/kg/day). Oral antihyperglycemic medications (OAMs): Metformin
dose at least 1500 milligram/day (mg/day) and/or sulfonylurea dose at least half the
maximum daily dose specified in the local package insert. OAM doses stable for 6 weeks
prior to the study.

- Hemoglobin A1c (HbA1c) less than or equal to 10.5% before randomization

- Body Mass Index (BMI) 19 to 45 kilogram/square meter (kg/m²)

- Capable and willing to prepare and inject insulin with a syringe while continuing to
use the prestudy OAMs, monitor own blood glucose; complete the study diary; be
receptive to diabetes education; comply with study visits and receive telephone calls
between visits

- Women of childbearing potential must test negative for pregnancy before receiving
treatment and agree to use reliable birth control until completing the follow-up visit
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Long-term use of short- or rapid-acting or premixed insulin within the 6 months before
the study. Short-term insulin therapy or occasional use are permitted

- Use of any glucose-lowering medications not allowed by the inclusion criteria in the 3
months before entry into the study

- Use of prescription or over-the-counter medications to promote weight loss within 3
months before entry into the study

- Current participation in a weight loss program, or plans to do so during the study

- Treatment with any antibody-based therapy within 6 months prior to the study

- Use of chronic (>14 consecutive days) systemic glucocorticoid therapy currently or
within 4 weeks prior to the study

- More than 1 episode of severe hypoglycemia within 6 months prior to the study, or
currently diagnosed with hypoglycemia unawareness

- 2 or more emergency room visits or hospitalizations due to poor glucose control in the
6 months preceding the study

- Liver disease

- History of renal transplantation, current renal dialysis, or creatinine >2.0
milligram/deciliter (mg/dL) (177 micromole/Liter [µmol]/L)

- Cardiac disease with a marked impact on physical functioning

- Clinically significant electrocardiogram (ECG) abnormalities at screening

- Malignancy other than basal cell or squamous cell skin cancer

- Fasting triglycerides >500 mg/dL

- Known diabetic autonomic neuropathy

- Known hypersensitivity or allergy to study insulin or its excipients

- Blood transfusion or severe blood loss within 3 months prior to entry into the study
or known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other
traits of hemoglobin abnormalities known to interfere with the HbA1c methodology

- Irregular sleep/wake cycle

- Women who are breastfeeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
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. - Coffs Harbour
Recruitment hospital [2] 0 0
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. - Keswick
Recruitment hospital [3] 0 0
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. - Ringwood East
Recruitment hospital [4] 0 0
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. - Fremantle
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
5035 - Keswick
Recruitment postcode(s) [3] 0 0
3135 - Ringwood East
Recruitment postcode(s) [4] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Idaho
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Hungary
State/province [4] 0 0
Budapest
Country [5] 0 0
Hungary
State/province [5] 0 0
Gyula
Country [6] 0 0
Hungary
State/province [6] 0 0
Veszprem
Country [7] 0 0
Poland
State/province [7] 0 0
Bialystok
Country [8] 0 0
Poland
State/province [8] 0 0
Lublin
Country [9] 0 0
Puerto Rico
State/province [9] 0 0
Hato Rey
Country [10] 0 0
Puerto Rico
State/province [10] 0 0
Manati
Country [11] 0 0
Puerto Rico
State/province [11] 0 0
San Juan
Country [12] 0 0
Romania
State/province [12] 0 0
Cluj-Napoca
Country [13] 0 0
Romania
State/province [13] 0 0
Iasi
Country [14] 0 0
Romania
State/province [14] 0 0
Targu Mures
Country [15] 0 0
Russian Federation
State/province [15] 0 0
Arkhangelsk
Country [16] 0 0
Russian Federation
State/province [16] 0 0
Moscow
Country [17] 0 0
Russian Federation
State/province [17] 0 0
Rostov-On-Don
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Saint Petersburg
Country [19] 0 0
Spain
State/province [19] 0 0
Alicante
Country [20] 0 0
Spain
State/province [20] 0 0
Dos Hermanas
Country [21] 0 0
Spain
State/province [21] 0 0
Malaga

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Comparison of fasting blood glucose levels in patients with Type 2 diabetes after 12 weeks of
treatment with a new basal insulin analog or with insulin glargine.
Trial website
https://clinicaltrials.gov/show/NCT01027871
Trial related presentations / publications
Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005 May;28(5):1245-9. Review.
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries