Clinical trial NCT02607306: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus.
Official title: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2015-11-18
Enrollment: 819
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Asia. The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide, insulin degludec and liraglutide in Japanese subjects with type 2 diabetes mellitus.


Eligibility criteria: Inclusion Criteria:

* Male or female Japanese subjects, age at least 20 years at the time of signing informed consent
* Type 2 diabetes subjects (diagnosed clinically) at least 6 months prior to screening
* HbA1c (glycosylated haemoglobin) 7.0-11.0 % (both inclusive) by central laboratory analysis, with the aim of a median of 8.3%. When approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c below or equal to 8.3%; or when approximately 50% of the randomised subjects have a HbA1c below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3%
* Body-mass index (BMI) above or equal to 20 kg/m\^2
* Subjects on stable therapy with one OAD (defined as unchanged medication and unchanged dose) for at least 60 days (metformin, a-GI, TZD, SU, SGLT2i or glinide) prior to screening according to approved Japanese labelling

Exclusion Criteria:

* Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness including gestational diabetes)
* Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 60 days before screening
* Anticipated initiation or change in concomitant medications in excess of 14 days known to affect weight or glucose metabolism
* Impaired liver function, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or above 2.5 times upper limit of normal
* Renal impairment estimated Glomerular Filtration Rate (eGFR) below 60mL/min/1.73m\^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
* Screening calcitonin equal to 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

Primary outcomes:
measure: Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Non-inferiority of IDegLira vs IDeg and Superiority of IDegLira vs Lira
timeFrame: Week 0, Week 52
Secondary outcomes:
measure: Change From Baseline in Body Weight (kg)
timeFrame: Week 0, Week 52
measure: Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
timeFrame: Weeks 0-52
measure: Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Superiority of IDegLira vs IDeg
timeFrame: Week 0, Week 52
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, Week 52
measure: Insulin Dose
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 7.0%
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment.
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 6.5%
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 6.5% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment.
timeFrame: After 52 weeks of treatment
measure: Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
timeFrame: After 52 weeks of treatment
measure: Change in Waist Circumference
timeFrame: Week 0, Week 52
measure: Change in Blood Pressure (Systolic and Diastolic)
timeFrame: Week 0, Week 52
measure: Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile)
timeFrame: After 52 weeks of the treatment
measure: Change in SMBG 9-point Profile - Mean of the 9-point Profile
timeFrame: Week 0, week 52
measure: Change in SMBG 9-point Profile - Mean of Postprandial Increments (From Before Meal to 90 Min After for Breakfast, Lunch and Dinner)
timeFrame: Week 0, week 52
measure: Total Cholesterol as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Low Density Lipoprotein (LDL) Cholesterol as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: High Density Lipoprotein (HDL) Cholesterol as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Very Low Density Lipoprotein (VLDL) Cholesterol as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Triglycerides as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Free Fatty Acids as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Fasting C-peptide as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Fasting Human Insulin as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Fasting Glucagon as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Proinsulin as a Ratio to Baseline at 52 Weeks
timeFrame: After 52 weeks of treatment
measure: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: 0-52 weeks
measure: Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: 0-52 weeks
measure: Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: 0-52 weeks
measure: Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition
timeFrame: 0-52 weeks
measure: Anti-drug Antibodies: Anti-insulin Degludec Antibodies
timeFrame: at week 52
measure: Anti-drug Antibodies: Number of Participants Positive or Negative for Anti-liraglutide Antibodies
timeFrame: at week 52
measure: Change in Clinical Evaluation: Fundoscopy or Fundus Photography
timeFrame: at screening (week -2 to week 0), at week 52
measure: Change in Clinical Evaluation: Electrocardiogram (ECG)
timeFrame: at screening (week -2 to week 0), at week 52
measure: Change in Clinical Evaluation: Pulse
timeFrame: Week 0, week 52
measure: Serum Concentrations of Insulin Degludec
timeFrame: Weeks 2, 8, 16, 26, 44, 52
measure: Plasma Concentrations of Liraglutide
timeFrame: Weeks 2, 8, 16, 26, 44, 52
Other outcomes:
Locations:
city: Adachi-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Akita-shi, Akita
country: Japan
facility: Novo Nordisk Investigational Site
city: Annaka-shi, Gunma
country: Japan
facility: Novo Nordisk Investigational Site
city: Asahikawa-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Chiba-shi, Chiba
country: Japan
facility: Novo Nordisk Investigational Site
city: Chitose, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Chuo-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Chuo-ku,Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Chuo-ku,
country: Japan
facility: Novo Nordisk Investigational Site
city: Edogawa-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Fujisawa-shi, Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Fukuoka-shi, Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Fukushima
country: Japan
facility: Novo Nordisk Investigational Site
city: Gunma
country: Japan
facility: Novo Nordisk Investigational Site
city: Hachioji-shi, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Ichihara-shi, Chiba
country: Japan
facility: Novo Nordisk Investigational Site
city: Iruma-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Itabashi-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Itabashi-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Izumisano-shi,Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Izumisano-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Kagoshima-shi, Kagoshima
country: Japan
facility: Novo Nordisk Investigational Site
city: Kamakura-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Kanra-gun, Gunma
country: Japan
facility: Novo Nordisk Investigational Site
city: Kashiwara-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Kawagoe-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kawaguchi-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kawasaki-shi,Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Kisarazu-shi, Chiba
country: Japan
facility: Novo Nordisk Investigational Site
city: Kobe-shi, Hyogo
country: Japan
facility: Novo Nordisk Investigational Site
city: Kuki-shi, Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Kumamoto-shi, Kumamoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Kumamoto-shi, Kumamoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Kumamoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Kushiro-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Kyoto-shi, Kyoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Minato-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Mito-shi, Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Mito-shi, Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Miura-shi, Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Miyazaki
country: Japan
facility: Novo Nordisk Investigational Site
city: Nagoya-shi, Aichi
country: Japan
facility: Novo Nordisk Investigational Site
city: Nagoya-shi, Aichi
country: Japan
facility: Novo Nordisk Investigational Site
city: Nishinomiya-shi, Hygo
country: Japan
facility: Novo Nordisk Investigational Site
city: Obihiro-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Obihiro-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Oita-shi
country: Japan
facility: Novo Nordisk Investigational Site
city: Okawa-shi, Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Onga-gun, Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Ota-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Saijo-shi, Ehime
country: Japan
facility: Novo Nordisk Investigational Site
city: Sapporo-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Sapporo-shi, Hokkaido
country: Japan
facility: Novo Nordisk Investigational Site
city: Sendai-shi, Miyagi
country: Japan
facility: Novo Nordisk Investigational Site
city: Sendai-shi, Miyagi
country: Japan
facility: Novo Nordisk Investigational Site
city: Shimotsuke-shi, Tochigi
country: Japan
facility: Novo Nordisk Investigational Site
city: Shizuoka-shi, Shizuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Tochigi
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Toshima-ku, Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Toyonaka-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Ube-shi, Yamaguchi
country: Japan
facility: Novo Nordisk Investigational Site
city: Urasoe-shi,
country: Japan
facility: Novo Nordisk Investigational Site
city: Yamaguchi-shi, Yamaguchi
country: Japan
facility: Novo Nordisk Investigational Site
city: Yamato-shi, Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Kaku K, Araki E, Tanizawa Y, Ross Agner B, Nishida T, Ranthe M, Inagaki N. Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naive Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial. Diabetes Obes Metab. 2019 Dec;21(12):2674-2683. doi: 10.1111/dom.13856. Epub 2019 Aug 28.
citation: 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.