A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 2 Diabetes Mellitus
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT03338010
Collaborator
(none)
536
32
2
23.9
16.8
0.7
Study Details
Study Description
Brief Summary
The purpose of this study is to compare long-acting basal insulin analog LY2963016 to Lantus® in insulin naïve adult Chinese participants with Type 2 Diabetes Mellitus (T2DM) on 2 or more oral antihyperglycemic medications (OAMs). Participants will continue their OAMs throughout the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
536 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 Adult Chinese Patients With Type 2 Diabetes Mellitus
Actual Study Start Date
:
Mar 22, 2018
Actual Primary Completion Date
:
Mar 18, 2020
Actual Study Completion Date
:
Mar 18, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY2963016 Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the fasting blood glucose (FBG) ≤100 milligram per deciliter (mg/dL) (5.6 millimoles per litre [mmol/L]) while avoiding hypoglycemia. Participants were allowed to continue oral antihyperglycemic medication (OAM). |
Drug: LY2963016
Administered SC
|
| Active Comparator: Lantus® Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
Drug: Lantus®
Administered SC
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 to Lantus®) [Baseline, Week 24]
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated by mixed-effects model for repeated measures (MMRM) with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model.
Secondary Outcome Measures
- Change From Baseline in HbA1c (Lantus® 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 by MMRM with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model.
- Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values [Baseline, Week 24]
Seven-point SMBG are completed at the following timepoints: Before Morning Meal, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, 2 Hours After Evening Meal and Bed Time. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.
- Percentage of Participants With HbA1c <7% at Week 24 [Week 24]
The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
- Percentage of Participants With HbA1c ≤6.5% at Week 24 [Week 24]
The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
- Change From Baseline in Glycemic Variability of Fasting Blood Glucose [Baseline, Week 24]
Glycemic variability is measured by the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning and daily pre-meal blood glucose value from the 7-point self-monitoring blood glucose [SMBG] profiles. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.
- Basal Insulin Dose Units Per Day [At Week 24]
Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.
- Change From Baseline in Basal Insulin Dose Units Per Day [Baseline, Week 24]
Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.
- Change From Baseline in Body Weight [Baseline, Week 24]
Change from baseline in body weight was evaluated. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.
- Insulin Treatment Satisfaction Questionnaire (ITSQ) [At Week 24]
ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items divided into 5 domains of satisfaction: Inconvenience of Regimen [(IR) 5 items: domain scores range (DSR) 5-35], Lifestyle Flexibility [(LF) 3 items: DSR 3-21], Glycemic Control [(GC) 3 items: DSR 3-21], Hypoglycemic Control [(HC) 5 items: DSR 5-35], Insulin Delivery Device [(IDD) 6 items: DSR 6-42]. All items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. ITSQ Total Overall Raw Scores range from 22-154. Both raw domain and overall scores are transformed on a scale of 0-100, where transformed score=100*[(7-mean raw score)/6]. Higher scores indicate better treatment satisfaction. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model.
- Number of Participants With Detectable Anti-Glargine Antibodies [Baseline through 24 weeks]
Number of participants with detectable anti-glargine antibodies were reported.
- Rate of Total Symptomatic and Nocturnal Hypoglycemia Events (Adjusted by 1 Year) [Baseline through 24 weeks]
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 (participant's treatment duration/365.25) as an offset variable. A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have T2DM based on the disease diagnostic criteria World Health Organization (WHO) classification.
-
Have been receiving 2 or more OAMs at stable doses for the 12 weeks prior to screening.
-
Have a HbA1c ≥7.0% and ≤11.0%.
-
Body mass index (BMI) ≤35 kilograms per meter squared.
Exclusion Criteria:
-
Have used insulin therapy (outside of pregnancy) anytime in the past 1 year, except for short-term treatment of acute conditions, and up to a maximum of 4 continuous weeks.
-
Have used any glucagon like peptide (GLP-1) receptor agonists within the previous 90 days.
-
Are currently taking traditional medicine (herbal medicine or patent medicine) with known/specified content of anti-hyperglycemic effects within 3 months before screening.
-
Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
-
Have had ≥2 emergency room visits or hospitalizations due to poor glucose control.
-
Have known hypersensitivity or allergy to Lantus® or its excipients.
-
Are receiving chronic systemic glucocorticoid therapy at pharmacological doses or have received such therapy within 4 weeks immediately preceding screening.
-
Have obvious signs or symptoms, or laboratory evidence, of liver disease.
-
Have one of the following concomitant diseases: significant cardiac or gastrointestinal disease.
-
Have a history of renal transplantation, are currently receiving renal dialysis or have a serum creatinine greater than 2.0 milligrams per deciliter.
-
Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia.
-
Participants with active cancer or personal history of cancer within the previous 5 years.
-
Are pregnant or intend to become pregnant during the course of the study.
-
Are women who are breastfeeding.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anhui Provincial Hospital | Hefei | Anhui | China | 230001 |
| 2 | The First Affiliated Hospital of Lanzhou University | Lanzhou | Gansu | China | 730000 |
| 3 | Shantou University Medical College No.2 Affiliated Hospital | Shantou | Guang Dong Province | China | 515041 |
| 4 | Guangdong Province People's Hospital | Guangzhou | Guangdong | China | 510080 |
| 5 | The First Affiliated Hospital, Sun-Yat Sen University | Guangzhou | Guangdong | China | 510080 |
| 6 | Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University | Guangzhou | Guangdong | China | 510120 |
| 7 | The 1st Affiliated Hospital of Henan Science and technology | Luoyang | Henan | China | 471003 |
| 8 | Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech | Wu Han | Hubei | China | 430030 |
| 9 | Wuhan Central Hospital | Wuhan | Hubei | China | 430014 |
| 10 | The First People Hospital of Yueyang | Yueyang | Hunan | China | 414000 |
| 11 | Changzhou No.2 People's Hospital | Changzhou | Jiangsu | China | 213003 |
| 12 | The Affliated Jiangyin Hospital of Southeast University Medical College | Jiangyin | Jiangsu | China | 214400 |
| 13 | Nanjing Drum Tower Hosp Affiliated Hosp of Nanjing Univ Med | Nanjing | Jiangsu | China | 210008 |
| 14 | The Second Affiliated Hospital of Nanjing Medical University | Nanjing | Jiangsu | China | 210011 |
| 15 | Nanjing First Hospital | Nanjing | Jiangsu | China | 210012 |
| 16 | Nanjing Jiangning Hospital | Nanjing | Jiangsu | China | 211199 |
| 17 | Wuxi People's Hospital | Wuxi | Jiangsu | China | 214023 |
| 18 | Xuzhou central Hospital | Xuzhou | Jiangsu | China | 221009 |
| 19 | Affiliated Hospital of Jiangsu University | Zhenjiang | Jiangsu | China | 212001 |
| 20 | No.2 Hospital Affiliated to Jilin University | Changchun City | Jilin | China | 130041 |
| 21 | Siping central people's hospital | Siping | Jilin | China | 136000 |
| 22 | Dalian Med. Univ. No 2 Affiliate Hospital | Dalian | Liao Ning | China | 116023 |
| 23 | Shengjing Hospital of China Medical University | Shenyang | Liaoning | China | 110022 |
| 24 | The First Affiliated Hospital with Nanjing Medical Universit | Nanjing | Nanjing | China | 210029 |
| 25 | General Hospital of Ningxia Medical University | Yinchuan | Ningxia | China | 750004 |
| 26 | 1st affiliated Hospital of Shanxi Medical University | Tai Yuan | Shan XI | China | 030001 |
| 27 | Jinan Central Hospital | Jinan | Shandong | China | 250013 |
| 28 | West China Hospital of Sichuan University | Chengdu | Sichuan | China | 610041 |
| 29 | Peking Union Medical College Hospital | Beijing | China | 88798 | |
| 30 | Chongqing General Hospital | Chongqing | China | 400013 | |
| 31 | Shanghai Putuo District Center Hospital | Shanghai | China | 200062 | |
| 32 | Tianjin Medical University General Hospital | Tianjin | China | 300052 |
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:
NCT03338010
Other Study ID Numbers:
- 16037
- I4L-GH-ABET
First Posted:
Nov 9, 2017
Last Update Posted:
May 25, 2021
Last Verified:
May 1, 2021
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 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the fasting blood glucose (FBG) ≤ 100 milligram per deciliter (mg/dL) (5.6 millimoles per litre [mmol/L]) while avoiding hypoglycemia. Participants were allowed to continue oral antihyperglycemic medication (OAM). | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Period Title: Overall Study | ||
| STARTED | 359 | 177 |
| Received at Least One Dose of Study Drug | 359 | 177 |
| COMPLETED | 336 | 159 |
| NOT COMPLETED | 23 | 18 |
Baseline Characteristics
| Arm/Group Title | LY2963016 | Lantus® | Total |
|---|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. | Total of all reporting groups |
| Overall Participants | 359 | 177 | 536 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.3
(9.6)
|
59.5
(8.9)
|
58.7
(9.4)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
150
41.8%
|
79
44.6%
|
229
42.7%
|
| Male |
209
58.2%
|
98
55.4%
|
307
57.3%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
359
100%
|
177
100%
|
536
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 |
359
100%
|
177
100%
|
536
100%
|
| Baseline Hemoglobin A1c (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Percentage of HbA1c] |
8.42
(1.04)
|
8.39
(0.92)
|
8.41
(1.00)
|
| Duration of Diabetes (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
10.09
(5.47)
|
10.69
(5.94)
|
10.29
(5.63)
|
Outcome Measures
| Title | Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 to Lantus®) |
|---|---|
| Description | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated by mixed-effects model for repeated measures (MMRM) with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study drug and had a baseline and at least one non-missing post-baseline HbA1c value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 334 | 158 |
| Least Squares Mean (Standard Error) [Percentage of HbA1c] |
-1.27
(0.043)
|
-1.23
(0.062)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | 0.40% noninferiority margin was used. | |
| Statistical Test of Hypothesis | p-Value | 0.545 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.19 to 0.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in HbA1c (Lantus® 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 by MMRM with baseline, insulin secretagogues at study entry, treatment, visit and treatment*visit in the model. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study drug and had a baseline and at least one non-missing post-baseline HbA1c value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 334 | 158 |
| Least Squares Mean (Standard Error) [Percentage of HbA1c] |
-1.27
(0.043)
|
-1.23
(0.062)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | 0.40% noninferiority margin was used. | |
| Statistical Test of Hypothesis | p-Value | 0.545 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.19 to 0.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values |
|---|---|
| Description | Seven-point SMBG are completed at the following timepoints: Before Morning Meal, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, 2 Hours After Evening Meal and Bed Time. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. |
| Time Frame | Baseline, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study drug and had a baseline and at least one non-missing post-baseline SMBG value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 337 | 159 |
| Before Morning Meal Glucose |
-48.7
(1.09)
|
-49.7
(1.59)
|
| 2 Hours After Morning Meal Glucose |
-56.3
(2.34)
|
-52.7
(3.39)
|
| Before Mid-Day Meal Glucose |
-43.2
(2.03)
|
-39.9
(2.93)
|
| 2 Hours After Mid-Day Meal Glucose |
-31.0
(2.31)
|
-35.9
(3.33)
|
| Before Evening Meal Glucose |
-32.1
(2.21)
|
-33.0
(3.19)
|
| 2 Hours After Evening Meal Glucose |
-29.7
(2.46)
|
-32.0
(3.55)
|
| Bedtime Glucose |
-31.6
(2.35)
|
-33.0
(3.40)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Before Morning Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.602 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.0 | |
| Confidence Interval |
(2-Sided) 95% -2.8 to 4.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | 2 Hours After Morning Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.373 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -3.7 | |
| Confidence Interval |
(2-Sided) 95% -11.8 to 4.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Before Mid-Day Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.351 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -3.3 | |
| Confidence Interval |
(2-Sided) 95% -10.3 to 3.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | 2 Hours After Mid-Day Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.230 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 4.9 | |
| Confidence Interval |
(2-Sided) 95% -3.1 to 12.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Before Evening Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.819 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.9 | |
| Confidence Interval |
(2-Sided) 95% -6.7 to 8.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | 2 Hours After Evening Meal Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.588 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 2.3 | |
| Confidence Interval |
(2-Sided) 95% -6.2 to 10.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Bedtime Glucose | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.732 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% -6.7 to 9.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With HbA1c <7% at Week 24 |
|---|---|
| Description | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study drug and had a baseline and at least one non-missing post-baseline HbA1c value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 334 | 158 |
| Number [Percentage of participants] |
43.7
12.2%
|
44.9
25.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.846 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants With HbA1c ≤6.5% at Week 24 |
|---|---|
| Description | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study drug and had a baseline and at least one non-missing post-baseline HbA1c value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 334 | 158 |
| Number [Percentage of participants] |
23.4
6.5%
|
16.5
9.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.098 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline in Glycemic Variability of Fasting Blood Glucose |
|---|---|
| Description | Glycemic variability is measured by the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning and daily pre-meal blood glucose value from the 7-point self-monitoring blood glucose [SMBG] profiles. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. |
| 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 at least one non-missing post-baseline SMBG value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 327 | 157 |
| Morning Pre-meal Standard Deviation |
-2.17
(0.606)
|
-2.49
(0.879)
|
| Daily Mean Standard Deviation |
-4.1
(0.85)
|
-4.5
(1.22)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Morning Pre-meal Standard Deviation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.767 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.32 | |
| Confidence Interval |
(2-Sided) 95% -1.78 to 2.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Daily Mean Standard Deviation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.781 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% -2.5 to 3.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Basal Insulin Dose Units Per Day |
|---|---|
| Description | Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. |
| Time Frame | At 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 at least one non-missing post-baseline basal Insulin dose value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 341 | 161 |
| Least Squares Mean (Standard Error) [units per day (U/day)] |
16.0
(0.43)
|
15.7
(0.61)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.750 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 1.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Basal Insulin Dose Units Per Day |
|---|---|
| Description | Units of basal insulin dose taken per day (U/day). LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. |
| 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 at least one non-missing post-baseline basal Insulin dose value. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 341 | 161 |
| Least Squares Mean (Standard Error) [U/day] |
7.0
(0.43)
|
6.8
(0.61)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.750 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.2 to 1.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Body Weight |
|---|---|
| Description | Change from baseline in body weight was evaluated. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. |
| 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 evaluable baseline and at least one non-missing post-baseline body weight data. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 334 | 158 |
| Least Squares Mean (Standard Error) [kilogram (kg)] |
1.1
(0.13)
|
1.2
(0.19)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Insulin Treatment Satisfaction Questionnaire (ITSQ) |
|---|---|
| Description | ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items divided into 5 domains of satisfaction: Inconvenience of Regimen [(IR) 5 items: domain scores range (DSR) 5-35], Lifestyle Flexibility [(LF) 3 items: DSR 3-21], Glycemic Control [(GC) 3 items: DSR 3-21], Hypoglycemic Control [(HC) 5 items: DSR 5-35], Insulin Delivery Device [(IDD) 6 items: DSR 6-42]. All items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. ITSQ Total Overall Raw Scores range from 22-154. Both raw domain and overall scores are transformed on a scale of 0-100, where transformed score=100*[(7-mean raw score)/6]. Higher scores indicate better treatment satisfaction. LS mean was calculated by MMRM with baseline, insulin secretagogues at study entry, baseline HbA1c, treatment, time and treatment*time in the model. |
| Time Frame | At Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study drug and had evaluable ITSQ data. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 334 | 158 |
| IR |
89.36
(0.80)
|
90.31
(1.16)
|
| LF |
83.70
(1.05)
|
87.69
(1.52)
|
| HC |
89.07
(0.79)
|
90.86
(1.15)
|
| GC |
87.80
(0.84)
|
87.83
(1.21)
|
| IDD |
86.84
(0.86)
|
88.29
(1.24)
|
| ITSQ Overall Total |
87.32
(0.75)
|
88.99
(1.08)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Inconvenience of Regimen Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.500 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.95 | |
| Confidence Interval |
(2-Sided) 95% -3.72 to 1.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Lifestyle Flexibility Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.031 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -3.99 | |
| Confidence Interval |
(2-Sided) 95% -7.62 to -0.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Hypoglycemic Control Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.200 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.79 | |
| Confidence Interval |
(2-Sided) 95% -4.53 to 0.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Glycemic Control Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.988 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.02 | |
| Confidence Interval |
(2-Sided) 95% -2.92 to 2.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | Insulin Delivery Device Satisfaction Transformed Score | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.337 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.45 | |
| Confidence Interval |
(2-Sided) 95% -4.41 to 1.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ITSQ Overall Total | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.205 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.67 | |
| Confidence Interval |
(2-Sided) 95% -4.26 to 0.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Detectable Anti-Glargine Antibodies |
|---|---|
| Description | Number of participants with detectable anti-glargine antibodies were reported. |
| Time Frame | Baseline through 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least 1 dose of study drug. Only participants with detected insulin antibody levels at baseline and at least one non-missing post-baseline were included in analysis. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 357 | 177 |
| Number [participants] |
69
19.2%
|
31
17.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.639 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Rate of Total Symptomatic and Nocturnal Hypoglycemia Events (Adjusted by 1 Year) |
|---|---|
| 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 (participant's treatment duration/365.25) as an offset variable. A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. |
| Time Frame | Baseline through 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had evaluable baseline and at least one non-missing post-baseline hypoglycemic event. |
| Arm/Group Title | LY2963016 | Lantus® |
|---|---|---|
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. |
| Measure Participants | 359 | 177 |
| Total hypoglycemia |
1.37
(0.228)
|
1.15
(0.280)
|
| Nocturnal Hypoglycemia |
0.47
(0.132)
|
0.39
(0.110)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.143 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Relative Ratio |
| Estimated Value | 1.19 | |
| Confidence Interval |
(2-Sided) 95% 0.74 to 1.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LY2963016, Lantus® |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.945 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Relative Ratio |
| Estimated Value | 1.22 | |
| Confidence Interval |
(2-Sided) 95% 0.67 to 2.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Baseline Up To 28 Weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All randomized 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 | Lantus® | ||
| Arm/Group Description | Insulin naive participants started on 10 U LY2963016 given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue OAM. | Insulin naive participants started on 10 U Lantus® given SC QD for 24 weeks. Participants-driven titration was supervised by investigators through the course of the study to maintain the FBG ≤100 mg/dL (5.6 mmol/L) while avoiding hypoglycemia. Participants were allowed to continue oral OAM. | ||
All Cause Mortality |
||||
| LY2963016 | Lantus® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/359 (0%) | 0/177 (0%) | ||
Serious Adverse Events |
||||
| LY2963016 | Lantus® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/359 (7.8%) | 14/177 (7.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Angina unstable | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Cardiac failure congestive | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Coronary artery disease | 1/359 (0.3%) | 1 | 1/177 (0.6%) | 1 |
| Ear and labyrinth disorders | ||||
| Sudden hearing loss | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Eye disorders | ||||
| Cataract | 2/359 (0.6%) | 2 | 0/177 (0%) | 0 |
| Malignant glaucoma | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Colitis | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Gastrointestinal polyp | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Haemorrhoids | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Large intestine polyp | 1/359 (0.3%) | 1 | 1/177 (0.6%) | 1 |
| Infections and infestations | ||||
| Central nervous system infection | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Gastroenteritis | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Hepatitis e | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Herpes zoster | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Pneumonia | 3/359 (0.8%) | 3 | 1/177 (0.6%) | 1 |
| Soft tissue infection | 1/359 (0.3%) | 1 | 1/177 (0.6%) | 1 |
| Urinary tract infection | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Facial bones fracture | 1/359 (0.3%) | 1 | 1/177 (0.6%) | 1 |
| Femoral neck fracture | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Fibula fracture | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Foot fracture | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Rib fracture | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Skin laceration | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Sternal fracture | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Metabolism and nutrition disorders | ||||
| Hypochloraemia | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Hypokalaemia | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Hyponatraemia | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Spinal osteoarthritis | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Breast cancer | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Lung neoplasm malignant | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Nervous system disorders | ||||
| Carotid artery stenosis | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Cerebral infarction | 5/359 (1.4%) | 6 | 2/177 (1.1%) | 2 |
| Renal and urinary disorders | ||||
| Calculus urethral | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Hydronephrosis | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Nephrolithiasis | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Ureterolithiasis | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 1/359 (0.3%) | 1 | 0/177 (0%) | 0 |
| Vascular disorders | ||||
| Hypertension | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
| Varicose vein | 0/359 (0%) | 0 | 1/177 (0.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| LY2963016 | Lantus® | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 194/359 (54%) | 95/177 (53.7%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia | 2/359 (0.6%) | 2 | 3/177 (1.7%) | 3 |
| Cardiac disorders | ||||
| Angina pectoris | 2/359 (0.6%) | 3 | 2/177 (1.1%) | 3 |
| Supraventricular extrasystoles | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Endocrine disorders | ||||
| Autoimmune thyroiditis | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Hypothyroidism | 4/359 (1.1%) | 4 | 1/177 (0.6%) | 2 |
| Eye disorders | ||||
| Cataract | 5/359 (1.4%) | 6 | 0/177 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Abdominal pain upper | 4/359 (1.1%) | 4 | 0/177 (0%) | 0 |
| Constipation | 6/359 (1.7%) | 6 | 3/177 (1.7%) | 3 |
| Diarrhoea | 10/359 (2.8%) | 14 | 4/177 (2.3%) | 4 |
| Nausea | 4/359 (1.1%) | 8 | 3/177 (1.7%) | 3 |
| Toothache | 9/359 (2.5%) | 11 | 1/177 (0.6%) | 1 |
| Vomiting | 4/359 (1.1%) | 4 | 1/177 (0.6%) | 1 |
| General disorders | ||||
| Chest discomfort | 2/359 (0.6%) | 2 | 3/177 (1.7%) | 3 |
| Chest pain | 7/359 (1.9%) | 7 | 2/177 (1.1%) | 2 |
| Hunger | 2/359 (0.6%) | 3 | 2/177 (1.1%) | 2 |
| Injection site pain | 15/359 (4.2%) | 19 | 5/177 (2.8%) | 5 |
| Injection site pruritus | 4/359 (1.1%) | 5 | 1/177 (0.6%) | 1 |
| Injection site rash | 4/359 (1.1%) | 7 | 1/177 (0.6%) | 1 |
| Oedema peripheral | 1/359 (0.3%) | 1 | 3/177 (1.7%) | 3 |
| Pyrexia | 4/359 (1.1%) | 4 | 1/177 (0.6%) | 1 |
| Hepatobiliary disorders | ||||
| Cholelithiasis | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Hepatic function abnormal | 3/359 (0.8%) | 3 | 3/177 (1.7%) | 3 |
| Hepatic steatosis | 3/359 (0.8%) | 3 | 4/177 (2.3%) | 4 |
| Infections and infestations | ||||
| Bronchitis | 3/359 (0.8%) | 3 | 6/177 (3.4%) | 6 |
| Gastroenteritis | 4/359 (1.1%) | 5 | 2/177 (1.1%) | 2 |
| Nasopharyngitis | 8/359 (2.2%) | 8 | 7/177 (4%) | 7 |
| Otitis media | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Periodontitis | 3/359 (0.8%) | 4 | 4/177 (2.3%) | 5 |
| Pharyngitis | 9/359 (2.5%) | 9 | 2/177 (1.1%) | 2 |
| Pneumonia | 2/359 (0.6%) | 2 | 3/177 (1.7%) | 4 |
| Pulpitis dental | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Respiratory tract infection | 5/359 (1.4%) | 6 | 0/177 (0%) | 0 |
| Upper respiratory tract infection | 73/359 (20.3%) | 80 | 32/177 (18.1%) | 38 |
| Urinary tract infection | 2/359 (0.6%) | 2 | 3/177 (1.7%) | 3 |
| Vaginal infection | 1/150 (0.7%) | 1 | 1/79 (1.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Head injury | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Limb injury | 2/359 (0.6%) | 2 | 2/177 (1.1%) | 2 |
| Investigations | ||||
| Blood pressure increased | 4/359 (1.1%) | 4 | 1/177 (0.6%) | 1 |
| Protein urine present | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Weight increased | 14/359 (3.9%) | 14 | 11/177 (6.2%) | 11 |
| Metabolism and nutrition disorders | ||||
| Hyperlipidaemia | 2/359 (0.6%) | 2 | 2/177 (1.1%) | 2 |
| Hypokalaemia | 4/359 (1.1%) | 6 | 1/177 (0.6%) | 1 |
| Hypoproteinaemia | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 5/359 (1.4%) | 5 | 2/177 (1.1%) | 2 |
| Joint effusion | 1/359 (0.3%) | 3 | 2/177 (1.1%) | 3 |
| Osteoarthritis | 2/359 (0.6%) | 2 | 3/177 (1.7%) | 3 |
| Pain in extremity | 2/359 (0.6%) | 2 | 2/177 (1.1%) | 2 |
| Periarthritis | 6/359 (1.7%) | 6 | 1/177 (0.6%) | 1 |
| Spinal osteoarthritis | 5/359 (1.4%) | 6 | 2/177 (1.1%) | 5 |
| Synovial cyst | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Nervous system disorders | ||||
| Carotid arteriosclerosis | 0/359 (0%) | 0 | 2/177 (1.1%) | 3 |
| Diabetic neuropathy | 1/359 (0.3%) | 1 | 5/177 (2.8%) | 5 |
| Dizziness | 8/359 (2.2%) | 10 | 3/177 (1.7%) | 3 |
| Hypoaesthesia | 2/359 (0.6%) | 2 | 2/177 (1.1%) | 2 |
| Psychiatric disorders | ||||
| Anxiety | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Depression | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Insomnia | 3/359 (0.8%) | 3 | 4/177 (2.3%) | 4 |
| Renal and urinary disorders | ||||
| Nephrolithiasis | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Renal cyst | 3/359 (0.8%) | 3 | 4/177 (2.3%) | 4 |
| Ureterolithiasis | 2/359 (0.6%) | 2 | 2/177 (1.1%) | 2 |
| Reproductive system and breast disorders | ||||
| Balanoposthitis | 0/209 (0%) | 0 | 1/98 (1%) | 1 |
| Prostatic calcification | 0/209 (0%) | 0 | 1/98 (1%) | 1 |
| Uterine atrophy | 0/150 (0%) | 0 | 1/79 (1.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 13/359 (3.6%) | 16 | 5/177 (2.8%) | 5 |
| Oropharyngeal pain | 3/359 (0.8%) | 4 | 4/177 (2.3%) | 4 |
| Pulmonary mass | 2/359 (0.6%) | 2 | 2/177 (1.1%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 4/359 (1.1%) | 4 | 0/177 (0%) | 0 |
| Rash | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Vascular disorders | ||||
| Aortic arteriosclerosis | 1/359 (0.3%) | 1 | 2/177 (1.1%) | 2 |
| Arteriosclerosis | 3/359 (0.8%) | 3 | 2/177 (1.1%) | 3 |
| Diabetic vascular disorder | 0/359 (0%) | 0 | 2/177 (1.1%) | 2 |
| Hypertension | 20/359 (5.6%) | 20 | 7/177 (4%) | 8 |
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:
NCT03338010
Other Study ID Numbers:
- 16037
- I4L-GH-ABET
First Posted:
Nov 9, 2017
Last Update Posted:
May 25, 2021
Last Verified:
May 1, 2021