A Double-blinded Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec Both in Combination With Metformin in Japanese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal or Pre-mix/Combination Insulin Therapy and Oral Anti-diabetic Drugs

NCT ID: NCT02911948

Last Updated: 2021-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-21
• Study Completion Date: 2017-11-22

Brief Summary

This trial is conducted in Asia. The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide and insulin degludec both in combination with metformin in Japanese subjects with type 2 diabetes mellitus inadequately controlled with basal or pre-mix/combination insulin therapy and oral anti-diabetic drugs.

Conditions

Diabetes; Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Insulin degludec/liraglutide

Group Type: EXPERIMENTAL

Insulin degludec/liraglutide

Intervention Type: DRUG

Injected s.c. / subcutaneously (under the skin) once daily

Insulin degludec

Group Type: ACTIVE_COMPARATOR

Insulin degludec

Intervention Type: DRUG

Injected s.c. / subcutaneously (under the skin) once daily

Interventions

Insulin degludec/liraglutide

Injected s.c. / subcutaneously (under the skin) once daily

Intervention Type: DRUG

Insulin degludec

Injected s.c. / subcutaneously (under the skin) once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female Japanese subjects, age at least 20 years at the time of signing informed consent
• T2DM (type 2 diabetes mellitus) subjects (diagnosed clinically) for at least 6 months prior to screening
• HbA1c (glycosylated haemoglobin) 7.5-11.0 per cent [58 mmol/mol-97 mmol/mol] (both inclusive) by central laboratory analysis
• Subjects on stable daily insulin doses for at least 60 days prior to screening administered once or twice daily, either as basal insulin (e.g. IDeg, insulin glargine, insulin detemir, NPH insulin) or pre-mix/combination insulin (e.g. biphasic insulin aspart, insulin degludec/insulin aspart). Total daily insulin dose in the previous 60 days should be within 20-50 units, both inclusive, and on the day of screening, but fluctuations of plus/minus 20 per cent within the 60 days prior to screening are acceptable. The specified insulin treatment should be administered in combination with a stable daily dose of metformin within current approved Japanese label for at least 60 days prior to screening - additionally, the anti-diabetic treatment can be with or without a stable daily dose of one of the following other OADs (oral anti-diabetic drug): SU (sulfonylureas), glinides, alpha-glucosidase inhibitor, SGLT2i (sodium glucose co-transporter 2 inhibitor) or TZD (thiazolidinedione) within current approved Japanese label for at least 60 days prior to screening
• Body Mass Index (BMI) equal or above 23 kg/m^2

Exclusion Criteria

• Receipt of any investigational medicinal product (IMP) within 30 days before screening
• Use of any anti-diabetic drug in a period of 60 days before screening (except premix/ combination or basal insulin, metformin, SU, glinides, α-GI, SGLT2i, or TZD) or anticipated change in concomitant medication, which in the investigators opinion could interfere with glucose metabolism (e.g. systemic corticosteroids or bolus insulin)
• Treatment with glucagon-like peptide-1 (GLP-1) receptor agonist during the last 60 days prior to screening and furthermore, the discontinuation of GLP-1 receptor agonist at any point in time must not have been due to safety concerns, tolerability issues or lack of efficacy, as judged by the investigator
• Treatment with dipetidyl peptidase-4 (DPP-4) inhibitors during the last 60 days prior to screening - Impaired liver function, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal or above 2.5 times upper limit of normal
• Renal impairment estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
• Screening calcitonin equal or above 50 ng/L
• History of pancreatitis (acute or chronic)
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
• Subjects presently classified as being in New York Heart Association (NYHA) Class IV

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Registry (GCR, 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Novo Nordisk Investigational Site

Asahikawa-shi, Hokkaido, , Japan

Novo Nordisk Investigational Site

Chigasaki-shi, Kanagawa, , Japan

Novo Nordisk Investigational Site

Chitose, Hokkaido, , Japan

Novo Nordisk Investigational Site

Chiyoda-ku, Tokyo, , Japan

Novo Nordisk Investigational Site

Fujisawa-shi, Kanagawa, , Japan

Novo Nordisk Investigational Site

Fukui-shi, Fukui, , Japan

Novo Nordisk Investigational Site

Fukuoka, , Japan

Novo Nordisk Investigational Site

Fukuoka-shi, Fukuoka, , Japan

Novo Nordisk Investigational Site

Fukuoka-shi, Fukuoka, , Japan

Novo Nordisk Investigational Site

Fukushima, , Japan

Novo Nordisk Investigational Site

Hokkaido, , Japan

Novo Nordisk Investigational Site

Ibaraki, , Japan

Novo Nordisk Investigational Site

Kanagawa, , Japan

Novo Nordisk Investigational Site

Kashiwara-shi, Osaka, , Japan

Novo Nordisk Investigational Site

Kawagoe-shi, Saitama, , Japan

Novo Nordisk Investigational Site

Kawaguchi-shi, Saitama, , Japan

Novo Nordisk Investigational Site

Kumamoto, , Japan

Novo Nordisk Investigational Site

Kumamoto-shi, Kumamoto, , Japan

Novo Nordisk Investigational Site

Mitaka-shi, Tokyo, , Japan

Novo Nordisk Investigational Site

Miyazaki, , Japan

Novo Nordisk Investigational Site

Nagano, , Japan

Novo Nordisk Investigational Site

Nakagami, Okinawa, , Japan

Novo Nordisk Investigational Site

Neyagawa-shi, Osaka, , Japan

Novo Nordisk Investigational Site

Niigata-shi, Niigata, , Japan

Novo Nordisk Investigational Site

Okawa-shi, Fukuoka, , Japan

Novo Nordisk Investigational Site

Osaka, , Japan

Novo Nordisk Investigational Site

Osaka-shi, Osaka, , Japan

Novo Nordisk Investigational Site

Ota-ku, Tokyo, , Japan

Novo Nordisk Investigational Site

Saitama-shi, Saitama, , Japan

Novo Nordisk Investigational Site

Sendai-shi, Miyagi, , Japan

Novo Nordisk Investigational Site

Shimotsuke-shi, Tochigi, , Japan

Novo Nordisk Investigational Site

Tochigi, , Japan

Novo Nordisk Investigational Site

Tokyo, , Japan

Novo Nordisk Investigational Site

Tokyo, , Japan

Novo Nordisk Investigational Site

Tokyo, , Japan

Novo Nordisk Investigational Site

Tomigusuku-shi, Okinawa, , Japan

Novo Nordisk Investigational Site

Tomigusuku-shi, Okinawa, , Japan

Novo Nordisk Investigational Site

Yamaguchi-shi, Yamaguchi, , Japan

Countries

Japan

References

Watada H, Kaneko S, Komatsu M, Agner BR, Nishida T, Ranthe M, Nakamura J. Superior HbA1c control with the fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with a maximum dose of 50 units of insulin degludec in Japanese individuals with type 2 diabetes in a phase 3, double-blind, randomized trial. Diabetes Obes Metab. 2019 Dec;21(12):2694-2703. doi: 10.1111/dom.13859. Epub 2019 Sep 17.

Reference Type: RESULT

PMID: 31423685 (View on PubMed)

Komatsu M, Watada H, Kaneko S, Ross Agner BF, Nishida T, Kaku K. Efficacy and safety of the fixed-ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type 2 diabetes: A subgroup analysis of two phase III trials. J Diabetes Investig. 2021 Sep;12(9):1610-1618. doi: 10.1111/jdi.13525. Epub 2021 Mar 24.

Reference Type: RESULT

PMID: 33595901 (View on PubMed)

Watada H, Ross Agner BF, Doshi A, Bardtrum L, Ranthe MF, Billings LK. IDegLira Improves Glycemic Control in Japanese Patients with Uncontrolled Type 2 Diabetes on Premixed Insulin Therapy. Diabetes Ther. 2020 Jan;11(1):331-339. doi: 10.1007/s13300-019-00730-y. Epub 2019 Nov 23.

Reference Type: DERIVED

PMID: 31760599 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1178-3453

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-163385

Identifier Type: OTHER

Identifier Source: secondary_id

NN9068-4184

Identifier Type: -

Identifier Source: org_study_id