A Study of LY2963016 Compared to Lantus® in Adult Chinese Participants With Type 1 Diabetes Mellitus

Type 1 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03338023
• Other study ID #: 16036
• Secondary ID: I4L-GH-ABES
• Status: Completed
• Phase: Phase 3
• Start date: March 23, 2018
• Est. completion date: March 5, 2020

Study information

• Verified date: April 15, 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: March 5, 2020
• Est. primary completion date: March 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• LY2963016
Administered SC
• Lantus®
Administered SC
• Insulin Lispro
Administered SC

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing
China	Peking University Peoples Hospital	Beijing	Beijing
China	No.2 Hospital Affiliated to Jilin University	Changchun City	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Changzhou No.2 People's Hospital	Changzhou	Jiangsu
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Dalian Med. Univ. No 2 Affiliate Hospital	Dalian	Liao Ning
China	Guangdong Province People's Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun-Yat Sen University	Guangzhou	Guangdong
China	First People's Hospital of Yunnan Province	Kunming	Yunnan
China	The 1st Affiliated Hospital of Henan Science and technology	Luoyang	Henan
China	Nanjing First Hospital	Nanjing	Jiangsu
China	The First Affiliated Hospital with Nanjing Medical Universit	Nanjing	Nanjing
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Shanghai Putuo District Center Hospital	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai
China	Shantou University Medical College No.2 Affiliated Hospital	Shantou	Guang Dong Province
China	Wu Han Tongji Hospital	Wu Han	Hu Bei
China	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®)	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).	Baseline, Week 24
Secondary	Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016)	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).	Baseline, Week 24
Secondary	Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values	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).	Baseline, Week 24
Secondary	Percentage of Participants With HbA1c <7%	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.	Week 24
Secondary	Percentage of Participants With HbA1c =6.5%	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.	Week 24
Secondary	Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG	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).	Baseline, Week 24
Secondary	Change From Baseline in Glycemic Variability of Fasting Blood Glucose	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).	Baseline, Week 24
Secondary	Change From Baseline in Basal Insulin Dose	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.	Baseline, Week 24
Secondary	Change From Baseline in Prandial Insulin Dose	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.	Baseline, Week 24
Secondary	Change From Baseline in Body Weight	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.	Baseline, Week 24
Secondary	Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ)	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).	Baseline, Week 24
Secondary	Number of Participants With Detectable Anti-Glargine Antibodies	Number of participants with detectable anti-glargine antibodies	Baseline through Week 24
Secondary	Rate of Documented Symptomatic Hypoglycemia	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.	Baseline through Week 24