A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 1 Diabetes Mellitus
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT03338023
Collaborator
(none)
272
20
2
23.4
13.6
0.6
Study Details
Study Description
Brief Summary
The purpose of this study is to compare long-acting basal insulin analog LY2963016 to Lantus® in combination with mealtime insulin lispro in adult Chinese participants with Type 1 Diabetes Mellitus (T1DM).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
272 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Prospective, Randomized, Open-Label Comparison of a Long-Acting Basal Insulin Analog, LY2963016, to Lantus® in Combination With Mealtime Insulin Lispro in Adult Chinese Patients With Type 1 Diabetes Mellitus
Actual Study Start Date
:
Mar 23, 2018
Actual Primary Completion Date
:
Mar 5, 2020
Actual Study Completion Date
:
Mar 5, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY2963016 + Insulin Lispro Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
Drug: LY2963016
Administered SC
Drug: Insulin Lispro
Administered SC
|
| Active Comparator: Lantus® + Insulin Lispro Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
Drug: Lantus®
Administered SC
Drug: Insulin Lispro
Administered SC
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®) [Baseline, Week 24]
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated using mixed-effects model for repeated measures (MMRM) with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time*Treatment (Type III sum of squares).
Secondary Outcome Measures
- Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016) [Baseline, Week 24]
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was calculated using MMRM with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time*Treatment (Type III sum of squares).
- Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values [Baseline, Week 24]
The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Before Morning Meal Glucose, 2 Hours After Morning Meal Glucose, Before Mid-Day Meal Glucose, 2 Hours After Mid-Day Meal Glucose, Before Evening Meal Glucose, Bedtime Glucose and 0300 Am Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).
- Percentage of Participants With HbA1c <7% [Week 24]
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
- Percentage of Participants With HbA1c ≤6.5% [Week 24]
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
- Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG [Baseline, Week 24]
Change From Baseline in Intrapatient blood glucose (BG). LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).
- Change From Baseline in Glycemic Variability of Fasting Blood Glucose [Baseline, Week 24]
Change From Baseline in Glycemic Variability of Fasting Blood Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares).
- Change From Baseline in Basal Insulin Dose [Baseline, Week 24]
Change from baseline in basal insulin dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.
- Change From Baseline in Prandial Insulin Dose [Baseline, Week 24]
Prandial Insulin Dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.
- Change From Baseline in Body Weight [Baseline, Week 24]
Change from baseline in body weight. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.
- Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) [Baseline, Week 24]
The ITSQ is a validated 22-item questionnaire that was used to assess treatment satisfaction. Items were measured on a 7-point scale, with lower scores reflecting better outcomes. In addition to an overall score, scores were also obtained for 5 domains, including inconvenience of regimen, lifestyle flexibility, glycemic control, hypoglycemic control, and insulin delivery device. Raw domain and overall scores were transformed on a scale from 0 to 100, where a higher score indicated better treatment satisfaction. LS mean was calculated using ANCOVA with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment (Type III sum of squares).
- Number of Participants With Detectable Anti-Glargine Antibodies [Baseline through Week 24]
Number of participants with detectable anti-glargine antibodies
- Rate of Documented Symptomatic Hypoglycemia [Baseline through Week 24]
Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). The overall yearly rates (events/participant/year) of those hypoglycemic events, calculated as, for each participant, the number of episodes times 365.25 and then divided by the participants treatment duration, will be summarized, and analyzed by a Negative-binomial regression model with treatment as fixed effects and log of (patient's treatment duration/365.25) as an offset variable.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have T1DM based on the disease diagnostic criteria (World Health Organization [WHO] Classification).
-
Have duration of T1DM ≥1 year.
-
Have HbA1c ≤11 %.
-
Have been administered with basal-bolus insulins or pre-mixed insulins for at least 90 days prior to screening.
-
Have a body mass index (BMI) ≤35 kilograms per meter squared.
Exclusion Criteria:
-
Exposure to an insulin glargine other than Lantus® within previous 30 days.
-
Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
-
Have had more than one episode of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within 6 months prior to entry into the study.
-
Have known hypersensitivity or allergy to any of the study insulins (Lantus® or insulin lispro) or to excipients of the study insulins.
-
Are pregnant, intend to become pregnant during the course of the study.
-
Women who are breastfeeding.
-
Are currently taking traditional medicine (herbal medicine or patent medicine) with known/specified content of anti-hyperglycemic effects within 3 months before screening.
-
Have congestive heart failure Class III and IV.
-
Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease.
-
Have any active cancer.
-
Have a history or diagnosis of human immunodeficiency virus (HIV) infection.
-
Have presence of clinically significant gastrointestinal disease.
-
Have a history of renal transplantation, or are currently receiving renal dialysis.
-
Are receiving chronic systemic glucocorticoid therapy at pharmacological doses.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University Peoples Hospital | Beijing | Beijing | China | 100044 |
| 2 | Shantou University Medical College No.2 Affiliated Hospital | Shantou | Guang Dong Province | China | 515041 |
| 3 | Guangdong Province People's Hospital | Guangzhou | Guangdong | China | 510080 |
| 4 | The First Affiliated Hospital, Sun-Yat Sen University | Guangzhou | Guangdong | China | 510080 |
| 5 | Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University | Guangzhou | Guangdong | China | 510120 |
| 6 | The 1st Affiliated Hospital of Henan Science and technology | Luoyang | Henan | China | 471003 |
| 7 | Wu Han Tongji Hospital | Wu Han | Hu Bei | China | 430030 |
| 8 | The Second Xiangya Hospital of Central South University | Changsha | Hunan | China | 410011 |
| 9 | Changzhou No.2 People's Hospital | Changzhou | Jiangsu | China | 213003 |
| 10 | The Second Affiliated Hospital of Nanjing Medical University | Nanjing | Jiangsu | China | 210011 |
| 11 | Nanjing First Hospital | Nanjing | Jiangsu | China | 210012 |
| 12 | Affiliated Hospital of Jiangsu University | Zhenjiang | Jiangsu | China | 212001 |
| 13 | No.2 Hospital Affiliated to Jilin University | Changchun City | Jilin | China | 130041 |
| 14 | Dalian Med. Univ. No 2 Affiliate Hospital | Dalian | Liao Ning | China | 116023 |
| 15 | The First Affiliated Hospital with Nanjing Medical Universit | Nanjing | Nanjing | China | 210029 |
| 16 | Shanghai Tenth People's Hospital | Shanghai | Shanghai | China | 200072 |
| 17 | West China Hospital of Sichuan University | Chengdu | Sichuan | China | 610041 |
| 18 | First People's Hospital of Yunnan Province | Kunming | Yunnan | China | 650034 |
| 19 | Peking Union Medical College Hospital | Beijing | China | 88798 | |
| 20 | Shanghai Putuo District Center Hospital | Shanghai | China | 200062 |
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
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT03338023
Other Study ID Numbers:
- 16036
- I4L-GH-ABES
First Posted:
Nov 9, 2017
Last Update Posted:
Mar 29, 2021
Last Verified:
Apr 15, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Period Title: Overall Study | ||
| STARTED | 137 | 135 |
| Received at Least One Dose of Study Drug | 137 | 135 |
| COMPLETED | 128 | 125 |
| NOT COMPLETED | 9 | 10 |
Baseline Characteristics
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro | Total |
|---|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Total of all reporting groups |
| Overall Participants | 137 | 135 | 272 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
41.8
(15.0)
|
41.4
(13.8)
|
41.6
(14.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
77
56.2%
|
66
48.9%
|
143
52.6%
|
| Male |
60
43.8%
|
69
51.1%
|
129
47.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
137
100%
|
135
100%
|
272
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
137
100%
|
135
100%
|
272
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| China |
137
100%
|
135
100%
|
272
100%
|
| Hemoglobin A1c (HbA1c) at Baseline (Percentage of HbA1c) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Percentage of HbA1c] |
7.90
(1.32)
|
7.85
(1.48)
|
7.88
(1.40)
|
| Duration of Diabetes in years (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
10.29
(9.53)
|
10.53
(9.53)
|
10.41
(9.51)
|
| Body Mass Index (BMI) (kilogram per meter square (kg/m²)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilogram per meter square (kg/m²)] |
21.90
(2.54)
|
22.03
(2.32)
|
21.96
(2.43)
|
Outcome Measures
| Title | Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®) |
|---|---|
| Description | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated using mixed-effects model for repeated measures (MMRM) with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time*Treatment (Type III sum of squares). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline HbA1c value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 127 | 125 |
| Least Squares Mean (Standard Error) [Percentage of HbA1c] |
-0.20
(0.071)
|
-0.08
(0.071)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | Noninferiority of LY2963016 to Lantus® was demonstrated at the 0.4% noninferiority margin and over 80 percent power. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 0.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016) |
|---|---|
| Description | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was calculated using MMRM with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time*Treatment (Type III sum of squares). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline HbA1c value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 127 | 125 |
| Least Squares Mean (Standard Error) [Percentage of HbA1c] |
-0.20
(0.071)
|
-0.08
(0.071)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | Noninferiority of Lantus® to LY2963016 was demonstrated at the 0.4% noninferiority margin. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.32 to 0.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values |
|---|---|
| Description | The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Before Morning Meal Glucose, 2 Hours After Morning Meal Glucose, Before Mid-Day Meal Glucose, 2 Hours After Mid-Day Meal Glucose, Before Evening Meal Glucose, Bedtime Glucose and 0300 Am Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline SMBG value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 127 | 124 |
| Before Morning Meal Glucose |
-7.2
(3.64)
|
-0.4
(3.68)
|
| 2 Hours After Morning Meal Glucose |
-10.6
(4.77)
|
-2.8
(4.83)
|
| Before Mid-Day Meal Glucose |
-4.6
(4.13)
|
8.5
(4.21)
|
| 2 Hours After Mid-Day Meal Glucose |
-1.6
(4.76)
|
1.9
(4.76)
|
| Before Evening Meal Glucose |
-6.2
(4.78)
|
4.8
(4.85)
|
| Bedtime Glucose |
-0.4
(4.99)
|
5.0
(5.06)
|
| 0300 Am Glucose |
-4.9
(3.87)
|
2.5
(3.94)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | Before Morning Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.191 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -6.8 | |
| Confidence Interval |
(2-Sided) 95% -17.0 to 3.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | 2 Hours After Morning Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.250 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -7.8 | |
| Confidence Interval |
(2-Sided) 95% -21.2 to 5.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | Before Mid-Day Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.028 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -13.1 | |
| Confidence Interval |
(2-Sided) 95% -24.7 to -1.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | 2 Hours After Mid-Day Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.599 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -3.6 | |
| Confidence Interval |
(2-Sided) 95% -16.8 to 9.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | Before Evening Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.109 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -11.0 | |
| Confidence Interval |
(2-Sided) 95% -24.4 to 2.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | Bedtime Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.452 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -5.4 | |
| Confidence Interval |
(2-Sided) 95% -19.4 to 8.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | 0300 Am Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.180 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -7.4 | |
| Confidence Interval |
(2-Sided) 95% -18.3 to 3.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With HbA1c <7% |
|---|---|
| Description | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had baseline and postbaseline HbA1c value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 127 | 125 |
| Number [percentage of participants] |
30.7
22.4%
|
32.8
24.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.787 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants With HbA1c ≤6.5% |
|---|---|
| Description | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had baseline and postbaseline HbA1c value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 127 | 125 |
| Number [percentage of participants] |
15.7
11.5%
|
22.4
16.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.201 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG |
|---|---|
| Description | Change From Baseline in Intrapatient blood glucose (BG). LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline SMBG value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 122 | 119 |
| Least Squares Mean (Standard Error) [mg/dL] |
-2.9
(1.33)
|
-2.6
(1.34)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.885 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 3.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Glycemic Variability of Fasting Blood Glucose |
|---|---|
| Description | Change From Baseline in Glycemic Variability of Fasting Blood Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline SMBG value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 122 | 119 |
| Morning Pre-meal Standard Deviation |
-9.0
(2.53)
|
-5.5
(2.56)
|
| Daily Mean Standard Deviation |
-10.4
(1.69)
|
-8.6
(1.71)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | Morning Pre-meal Standard Deviation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.328 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -3.5 | |
| Confidence Interval |
(2-Sided) 95% -10.6 to 3.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | Daily Mean Standard Deviation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.467 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -6.5 to 3.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Basal Insulin Dose |
|---|---|
| Description | Change from baseline in basal insulin dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline Basal Insulin dose value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 129 | 127 |
| Least Squares Mean (Standard Error) [Units per Day (U/day)] |
0.7
(0.33)
|
1.5
(0.33)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.090 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to 0.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Prandial Insulin Dose |
|---|---|
| Description | Prandial Insulin Dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline Prandial Insulin dose value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 129 | 127 |
| Least Squares Mean (Standard Error) [U/day] |
0.2
(0.49)
|
1.4
(0.50)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.089 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -2.6 to 0.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Body Weight |
|---|---|
| Description | Change from baseline in body weight. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline weight value. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 128 | 125 |
| Least Squares Mean (Standard Error) [kilograms (kg)] |
0.8
(0.21)
|
0.9
(0.22)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.770 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to 0.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) |
|---|---|
| Description | The ITSQ is a validated 22-item questionnaire that was used to assess treatment satisfaction. Items were measured on a 7-point scale, with lower scores reflecting better outcomes. In addition to an overall score, scores were also obtained for 5 domains, including inconvenience of regimen, lifestyle flexibility, glycemic control, hypoglycemic control, and insulin delivery device. Raw domain and overall scores were transformed on a scale from 0 to 100, where a higher score indicated better treatment satisfaction. LS mean was calculated using ANCOVA with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment (Type III sum of squares). |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had a baseline and postbaseline ITSQ score. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 130 | 131 |
| ITSQ Inconvenience of Regimen Transformed Score |
3.5
(1.30)
|
3.8
(1.29)
|
| ITSQ Lifestyle Flexibility Transformed Score |
1.3
(1.86)
|
2.0
(1.86)
|
| ITSQ Hypoglycemic Control Transformed Score |
3.2
(1.39)
|
3.8
(1.38)
|
| ITSQ Glycemic Control Transformed Score |
6.9
(1.64)
|
6.0
(1.64)
|
| ITSQ Insulin Delivery Device Satisfaction Transformed Score |
3.3
(1.26)
|
2.9
(1.26)
|
| ITSQ Total Transformed Score |
3.3
(1.10)
|
4.1
(1.10)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ITSQ Inconvenience of Regimen Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.879 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -3.9 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ITSQ Lifestyle Flexibility Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.788 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.7 | |
| Confidence Interval |
(2-Sided) 95% -5.9 to 4.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ITSQ Hypoglycemic Control Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.775 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -4.5 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ITSQ Glycemic Control Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.681 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 1.0 | |
| Confidence Interval |
(2-Sided) 95% -3.6 to 5.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ITSQ Insulin Delivery Device Satisfaction Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.819 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 3.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | LY2963016 + Insulin Lispro, Lantus® + Insulin Lispro |
|---|---|---|
| Comments | ITSQ Total Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.605 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.8 | |
| Confidence Interval |
(2-Sided) 95% -3.9 to 2.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Detectable Anti-Glargine Antibodies |
|---|---|
| Description | Number of participants with detectable anti-glargine antibodies |
| Time Frame | Baseline through Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug.Only participants with detected or non-detected insulin antibody levels at baseline and post-baseline were included in analysis. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 136 | 134 |
| Detectable Anti-Glargine Antibodies |
76
55.5%
|
68
50.4%
|
| Detectable Cross Reactive Insulin Antibodies |
67
48.9%
|
58
43%
|
| Treatment Emergent Antibody Response (TEAR) |
42
30.7%
|
35
25.9%
|
| Title | Rate of Documented Symptomatic Hypoglycemia |
|---|---|
| Description | Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). The overall yearly rates (events/participant/year) of those hypoglycemic events, calculated as, for each participant, the number of episodes times 365.25 and then divided by the participants treatment duration, will be summarized, and analyzed by a Negative-binomial regression model with treatment as fixed effects and log of (patient's treatment duration/365.25) as an offset variable. |
| Time Frame | Baseline through Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug. |
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro |
|---|---|---|
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. |
| Measure Participants | 137 | 135 |
| Least Squares Mean (Standard Error) [events/participant/year] |
12.6
(2.42)
|
14.0
(2.64)
|
Adverse Events
| Time Frame | Baseline Up To 28 Weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly. | |||
| Arm/Group Title | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro | ||
| Arm/Group Description | Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | ||
All Cause Mortality |
||||
| LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/137 (0%) | 0/135 (0%) | ||
Serious Adverse Events |
||||
| LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/137 (6.6%) | 8/135 (5.9%) | ||
| Cardiac disorders | ||||
| Coronary artery disease | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Eye disorders | ||||
| Diabetic retinopathy | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Diabetic gastroenteropathy | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Infections and infestations | ||||
| Bronchitis | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Gastroenteritis | 1/137 (0.7%) | 1 | 1/135 (0.7%) | 1 |
| Pneumonia | 0/137 (0%) | 0 | 2/135 (1.5%) | 2 |
| Pulmonary tuberculosis | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Tonsillitis | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Urinary tract infection | 0/137 (0%) | 0 | 1/135 (0.7%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Spinal fracture | 0/137 (0%) | 0 | 1/135 (0.7%) | 1 |
| Metabolism and nutrition disorders | ||||
| Diabetic ketoacidosis | 1/137 (0.7%) | 1 | 1/135 (0.7%) | 1 |
| Hypoglycaemia | 2/137 (1.5%) | 2 | 3/135 (2.2%) | 4 |
| Nervous system disorders | ||||
| Diabetic neuropathy | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Hypoglycaemic coma | 1/137 (0.7%) | 1 | 0/135 (0%) | 0 |
| Renal and urinary disorders | ||||
| Nephritis | 0/137 (0%) | 0 | 1/135 (0.7%) | 1 |
| Perinephritis | 0/137 (0%) | 0 | 1/135 (0.7%) | 1 |
| Ureterolithiasis | 1/137 (0.7%) | 1 | 1/135 (0.7%) | 1 |
| Reproductive system and breast disorders | ||||
| Ovarian disorder | 1/77 (1.3%) | 1 | 0/66 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 84/137 (61.3%) | 77/135 (57%) | ||
| Blood and lymphatic system disorders | ||||
| Lymphadenitis | 1/137 (0.7%) | 1 | 2/135 (1.5%) | 2 |
| Cardiac disorders | ||||
| Palpitations | 0/137 (0%) | 0 | 2/135 (1.5%) | 2 |
| Eye disorders | ||||
| Diabetic retinopathy | 3/137 (2.2%) | 3 | 0/135 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 2/137 (1.5%) | 3 | 1/135 (0.7%) | 1 |
| Abdominal pain upper | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Diarrhoea | 7/137 (5.1%) | 9 | 3/135 (2.2%) | 4 |
| Toothache | 2/137 (1.5%) | 2 | 6/135 (4.4%) | 6 |
| General disorders | ||||
| Chest discomfort | 1/137 (0.7%) | 1 | 2/135 (1.5%) | 2 |
| Chest pain | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Injection site haemorrhage | 2/137 (1.5%) | 2 | 0/135 (0%) | 0 |
| Injection site pain | 4/137 (2.9%) | 4 | 7/135 (5.2%) | 17 |
| Pyrexia | 1/137 (0.7%) | 1 | 3/135 (2.2%) | 3 |
| Hepatobiliary disorders | ||||
| Hepatic function abnormal | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Immune system disorders | ||||
| Hypersensitivity | 2/137 (1.5%) | 3 | 0/135 (0%) | 0 |
| Infections and infestations | ||||
| Bronchitis | 4/137 (2.9%) | 4 | 2/135 (1.5%) | 2 |
| Conjunctivitis | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Gastroenteritis | 0/137 (0%) | 0 | 4/135 (3%) | 4 |
| Influenza | 3/137 (2.2%) | 4 | 2/135 (1.5%) | 2 |
| Nasopharyngitis | 12/137 (8.8%) | 15 | 14/135 (10.4%) | 18 |
| Pharyngitis | 1/137 (0.7%) | 1 | 4/135 (3%) | 5 |
| Upper respiratory tract infection | 34/137 (24.8%) | 43 | 23/135 (17%) | 29 |
| Urinary tract infection | 5/137 (3.6%) | 5 | 2/135 (1.5%) | 2 |
| Injury, poisoning and procedural complications | ||||
| Joint injury | 2/137 (1.5%) | 2 | 0/135 (0%) | 0 |
| Ligament sprain | 0/137 (0%) | 0 | 3/135 (2.2%) | 3 |
| Thermal burn | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Investigations | ||||
| Blood creatinine increased | 2/137 (1.5%) | 2 | 0/135 (0%) | 0 |
| Blood urea increased | 2/137 (1.5%) | 2 | 0/135 (0%) | 0 |
| Platelet count decreased | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Weight increased | 4/137 (2.9%) | 4 | 4/135 (3%) | 4 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 3/137 (2.2%) | 3 | 0/135 (0%) | 0 |
| Electrolyte imbalance | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Hyperuricaemia | 2/137 (1.5%) | 2 | 0/135 (0%) | 0 |
| Hypokalaemia | 0/137 (0%) | 0 | 2/135 (1.5%) | 3 |
| Hypoproteinaemia | 0/137 (0%) | 0 | 2/135 (1.5%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Pain in extremity | 2/137 (1.5%) | 2 | 1/135 (0.7%) | 1 |
| Nervous system disorders | ||||
| Dizziness | 3/137 (2.2%) | 3 | 3/135 (2.2%) | 3 |
| Headache | 2/137 (1.5%) | 2 | 2/135 (1.5%) | 2 |
| Psychiatric disorders | ||||
| Insomnia | 3/137 (2.2%) | 3 | 1/135 (0.7%) | 1 |
| Reproductive system and breast disorders | ||||
| Azoospermia | 1/60 (1.7%) | 1 | 0/69 (0%) | 0 |
| Dysmenorrhoea | 1/77 (1.3%) | 1 | 0/66 (0%) | 0 |
| Prostatitis | 1/60 (1.7%) | 1 | 0/69 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 5/137 (3.6%) | 5 | 3/135 (2.2%) | 3 |
| Oropharyngeal pain | 3/137 (2.2%) | 3 | 2/135 (1.5%) | 2 |
| Rhinorrhoea | 3/137 (2.2%) | 3 | 1/135 (0.7%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 3/137 (2.2%) | 3 | 2/135 (1.5%) | 2 |
| Urticaria | 1/137 (0.7%) | 1 | 2/135 (1.5%) | 2 |
| Vascular disorders | ||||
| Hypertension | 4/137 (2.9%) | 4 | 1/135 (0.7%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| ClinicalTrials.gov@lilly.com |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT03338023
Other Study ID Numbers:
- 16036
- I4L-GH-ABES
First Posted:
Nov 9, 2017
Last Update Posted:
Mar 29, 2021
Last Verified:
Apr 15, 2020