A Trial Comparing the Efficacy and Safety of Liraglutide 1.8 mg/Day to Liraglutide 0.9 mg/Day in Japanese Subjects With Type 2 Diabetes Mellitus.

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A Trial Comparing the Efficacy and Safety of Liraglutide 1.8 mg/Day to Liraglutide 0.9 mg/Day in Japanese Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02505334
• Other study ID #: NN2211-4174
• Secondary ID: U1111-1164-5462J
• Status: Completed
• Phase: Phase 3
• Start date: July 21, 2015
• Est. completion date: November 9, 2017

Study information

• Verified date: July 2018
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Asia. The aim of the trial is to compare the efficacy and safety of liraglutide 1.8 mg/day to liraglutide 0.9 mg/day in Japanese subjects with type 2 diabetes mellitus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 635
• Est. completion date: November 9, 2017
• Est. primary completion date: May 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Male or female Japanese subjects at least 20 years of age at the time of informed consent

• Type 2 diabetes subjects (diagnosed clinically) for at least 6 months prior to screening

• HbA1c 7.5-10.0% [58 mmol/mol-86 mmol/mol] (both inclusive)

• Subjects on stable therapy with one OAD (oral antidiabetic drug) (stable therapy is defined as unchanged medication and unchanged dose) for for at least 60 days before screening according to approved Japanese labelling

Exclusion Criteria:

• Treatment with insulin within 12 weeks prior to screening

• 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

• 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

• Within the past 180 days any of the following: myocardial infarction, stroke or hospitalisation for unstable angina and/or transient ischemic attack

• Diagnosis of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer, polyps and in-situ carcinomas)

• Any condition which, in the opinion of the investigator might jeopardise subject's safety or compliance with the protocol

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
Injected subcutaneously s.c. (under the skin) once daily.

Locations

Country	Name	City	State
Japan	Novo Nordisk Investigational Site	Annaka-shi, Gunma
Japan	Novo Nordisk Investigational Site	Chitose, Hokkaido
Japan	Novo Nordisk Investigational Site	Chuo-ku Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku,
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Fukuoka-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Higashiosaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Hokkaido
Japan	Novo Nordisk Investigational Site	Ichikawa-shi, Chiba
Japan	Novo Nordisk Investigational Site	Iruma-shi, Saitama
Japan	Novo Nordisk Investigational Site	Izumisano-shi
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Kawagoe-shi, Saitama
Japan	Novo Nordisk Investigational Site	Kobe-shi, Hyogo
Japan	Novo Nordisk Investigational Site	Kumamoto-shi,Kumamoto
Japan	Novo Nordisk Investigational Site	Mito-shi, Ibaraki
Japan	Novo Nordisk Investigational Site	Mito-shi, Ibaraki
Japan	Novo Nordisk Investigational Site	Miyazaki-shi
Japan	Novo Nordisk Investigational Site	Naka-shi, Ibaraki
Japan	Novo Nordisk Investigational Site	Neyagawa-shi, Osaka
Japan	Novo Nordisk Investigational Site	Nishinomiya-shi, Hygo
Japan	Novo Nordisk Investigational Site	Nishinomiya-shi, Hyogo
Japan	Novo Nordisk Investigational Site	Oita-shi
Japan	Novo Nordisk Investigational Site	Okawa-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Osaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Osaka-shi, Osaka
Japan	Novo Nordisk Investigational Site	Oyama-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Saga-shi,Saga
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Sappro-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Shimotsuke-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Shizuoka-shi
Japan	Novo Nordisk Investigational Site	Suita-shi, Osaka
Japan	Novo Nordisk Investigational Site	Takatsuki-shi, Osaka
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Yokohama, Kanagawa
Japan	Novo Nordisk Investigational Site	Yokohama-shi
Japan	Novo Nordisk Investigational Site	Yokohama-shi Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Haemoglobin (HbA1c) (Week 26)	Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated after 26 weeks of treatment. The change from baseline in the response after 26 weeks of treatment is analysed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and baseline response as a covariate.	Week 0, Week 26
Secondary	Change in HbA1c (Week 52)	Change from baseline (week 0) in HbA1c was evaluated after 52 weeks of treatment.	Week 0, Week 52
Secondary	Responder for HbA1c Below 7.0% (53 mmol/Mol)	Reported results are number of subjects who achieved HbA1c target below 7.0% after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Responder for HbA1c Below or Equal to 6.5% (48 mmol/Mol)	Reported results are number of subjects who achieved HbA1c target below or equal to 6.5% after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Responder for HbA1c Below 7.0% Without Weight Gain	Reported results are number of subjects who achieved HbA1c target below 7.0% without weight gain after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Responder for HbA1c Below 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	Reported results are subjects with HbA1c <7.0% after 26 weeks and 52 weeks of treatment, respectively without treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes. Severe or BG confirmed symptomatic hypoglycaemia: severe as per ADA classification or BG confirmed by plasma glucose (PG) value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA: episode requiring assistance of another person to actively administer carbohydrate/glucagon, or take other corrective actions. PG levels may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG level. Treatment emergent: episode with onset date on or after randomisation (from week (wk)0) and no later than 7 days after the last day on liraglutide (maximum till wk26+7days and wk52+7days). Hence, the following shown 'Time Frame' should be read as 'Wk26+7days and Wk52+7days'	Week 26 and Week 52
Secondary	Change in Self-Measured Blood Glucose (SMBG) 7-point Profile: 7-point Profile (Individual Points in the Profile)	Reported results are 7-point SMBG values at week 0, week 26 and week 52. The 7-point profile blood glucose levels were measured at the following time points always starting with the first: Before breakfast.; 90 minutes after start of breakfast.; Before lunch.; 90 minutes after start of lunch.; Before dinner.; 90 minutes after start of dinner.; At bedtime.	Week 0 and Week 26 and Week 52
Secondary	Change in SMBG 7-point Profile: Mean of 7-point Profile	Change from baseline (week 0) in mean of the SMBG 7-point profile was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in SMBG 7-point Profile: Mean of Postprandial Increments (From Before Meal to 90 Minutes After for Breakfast, Lunch and Dinner)	Change from baseline (week 0) in mean of postprandial increments (from before meal to 90 minutes after for breakfast, lunch and dinner) of the SMBG 7-point profile was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Fasting Plasma Glucose (FPG)	Change from baseline (week 0) in FPG was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Waist Circumference	Change from baseline (week 0) in waist circumference was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Body Weight	Change from baseline (week 0) in body weight was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Body Mass Index (BMI)	Change from baseline (week 0) in BMI was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Blood Pressure (Systolic and Diastolic)	Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Fasting C-peptide	Fasting C-peptide was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Fasting Insulin	Fasting insulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Fasting Glucagon	Fasting glucagon was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Proinsulin	Proinsulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Proinsulin/Insulin	Proinsulin/insulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Homeostasis Model Assessment of Beta-cell Function (HOMA-B)	HOMA-B was evaluated after 26 weeks and 52 weeks of treatment, respectively. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B=[(20 x fasting insulin in µU/mL)/(FPG in mmol/L-3.5)].	Week 26 and Week 52
Secondary	Homeostasis Model Assessment as an Index of Insulin Resistance (HOMA-IR)	HOMA-IR was evaluated after 26 weeks and 52 weeks of treatment, respectively. HOMA-IR is an index of insulin resistance and was calculated as: HOMA-IR= fasting insulin (µU/mL) x FPG (mmol/L)/22.5.	Week 26 and Week 52
Secondary	Total Cholesterol	Total cholesterol was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Low Density Lipoprotein (LDL) Cholesterol	LDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	High Density Lipoprotein (HDL) Cholesterol	HDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Very Low Density Lipoprotein (VLDL) Cholesterol	VLDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Triglycerides	Triglycerides were evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Free Fatty Acids	Free fatty acids were evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 26 and Week 52
Secondary	Number of Treatment Emergent Adverse Events	Treatment emergent adverse events (TEAEs) were evaluated during the 26-week and 52-week treatment period, respectively. TEAE for weeks 0-26: Event that has onset date on or after randomisation (from week 0) and no later than seven days after the last day on liraglutide (maximum till week 26 + 7 days). TEAE for weeks 0-52: Event that has onset date on or after randomisation (from week 0) and no later than seven days after the last day on liraglutide (maximum till week 52 + 7 days). Hence, the following shown 'Time Frame' should be read as 'Weeks 0-26 + 7 days and Weeks 0-52 + 7 days'.	Weeks 0-26 and Weeks 0-52
Secondary	Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were evaluated during the 26-week and 52-week treatment period, respectively. Severe or BG confirmed symptomatic hypoglycaemia (hypo):An episode that was severe according to the ADA classification or BG confirmed by a PG value <3.1 mmol/L with symptoms consistent with hypo. ADA definition of severe hypo:episode requiring assistance of another person to actively administer carbohydrate/glucagon, or take other corrective actions. PG levels may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG level. Treatment emergent: episode with onset date on or after randomisation (from week (wk) 0) and no later than 7 days after the last day on liraglutide (maximum till wk 26 and wk 52, respectively + 7 days). Hence, the following shown 'Time Frame' should be read as 'wk 0-26+7 days and wk 0-52+7 days'.	Weeks 0-26 and Weeks 0-52
Secondary	Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	Treatment emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes were evaluated during the26-week and 52-week treatment period, respectively. Nocturnal hypoglycaemic episodes: Those occurring between 00:01 and 05:59 hours, both inclusive. Severe or BG confirmed symptomatic hypoglycaemia: episode that was severe according to the ADA classification or BG confirmed by a PG value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Treatment emergent: episode with onset date on or after randomisation (from week 0) and no later than 7 days after the last day on liraglutide (maximum till week 26 and week 52, respectively + 7 days). Hence, the following shown 'Time Frame' should be read as 'Week 0-26 + 7 days and Week 0-52 + 7 days'.	Weeks 0-26 and Weeks 0-52
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition	American Diabetes Association (ADA) classification of hypoglycaemia: Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level.; Documented symptomatic: PG level =3.9 mmol/L with symptoms.; Asymptomatic: PG level =3.9 mmol/L without symptoms.; Probable symptomatic: No measurement with symptoms.; Pseudo: PG level >3.9 mmol/L with symptoms. Treatment emergent hypoglycaemic episode: episode with onset date on or after randomisation (from week 0) and no later than 7 days after the last day on liraglutide (maximum till week 26 and week 52, respectively + 7 days). Hence, the following shown 'Time Frame' should be read as 'Week 0-26 + 7 days and Week 0-52 + 7 days'.	Weeks 0-26 and Weeks 0-52
Secondary	Change in Pulse	Change from baseline (week 0) in pulse was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Physical Examination	Reported results are physical examination outcomes at week (wk) 0, wk 26 and wk 52. Physical examination consisted of the following listed examinations and the outcome of each examination was evaluated as: 1) normal, 2) abnormal, not clinically significant (NCS) or 3) abnormal, clinically significant (CS).; Cardiovascular system; Central and peripheral nervous system (PNS); Gastrointestinal (GI) system including mouth; General appearance; Head, ears, eyes, nose, throat, neck; Lymph node palpation; Musculoskeletal system; Respiratory system; Skin; Thyroid gland	Week 0 and Week 26 and Week 52
Secondary	Change in Eye Examination	Reported results are eye examination (ophthalmoscopy) outcomes at week 0, week 26 and week 52. Ophthalmoscopy outcomes for both left and right eye were evaluated as: 1) normal, 2) abnormal, NCS or 3) abnormal, CS.	Week 0 and Week 26 and Week 52
Secondary	Change in Electrocardiogram (ECG)	Reported results are ECG outcomes at week 0, week 26 and week 52. ECG outcomes were evaluated as: 1) normal, 2) abnormal, NCS or 3) abnormal, CS.	Week 0 and Week 26 and Week 52
Secondary	Change in Biochemistry: Creatinine	Change from baseline (week 0) in creatinine was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: eGFR	Change from baseline (week 0) in estimated glomerular filtration rate (eGFR) was evaluated after 26 weeks and 52 weeks of treatment, respectively. eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, mL/min/1.73m^2.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Alanine Aminotransferase	Change from baseline (week 0) in alanine aminotransferase was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Aspartate Aminotransferase	Change from baseline (week 0) in aspartate aminotransferase was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Alkaline Phosphatase	Change from baseline (week 0) in alkaline phosphatase was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Sodium	Change from baseline (week 0) in sodium was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Potassium	Change from baseline (week 0) in potassium was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Albumin	Change from baseline (week 0) in albumin was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Total Bilirubin	Change from baseline (week 0) in total bilirubin was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Urea	Change from baseline (week 0) in urea was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Creatine Kinase	Change from baseline (week 0) in creatine kinase was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Calcium	Change from baseline (week 0) in calcium was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Albumin Corrected Calcium	Change from baseline (week 0) in albumin corrected calcium was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Amylase	Change from baseline (week 0) in amylase was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Biochemistry: Lipase	Change from baseline (week 0) in lipase was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Haematology: Haemoglobin	Change from baseline (week 0) in haemoglobin was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26, Week 52
Secondary	Change in Haematology: Haematocrit	Change from baseline (week 0) in haematocrit was evaluated after 26 weeks and 52 weeks of treatment, respectively. Haematocrit is the ratio of the volume of red blood cells to the total volume of blood.	Week 0, Week 26, Week 52
Secondary	Change in Haematology: Thrombocytes	Change from baseline (week 0) in thrombocytes (platelets) was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Haematology: Erythrocytes	Change from baseline (week 0) in erythrocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Haematology: Leukocytes	Change from baseline (week 0) in leukocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Haematology: Eosinophils	Change from baseline (week 0) in eosinophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Haematology: Neutrophils	Change from baseline (week 0) in neutrophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Haematology: Basophils	Change from baseline (week 0) in basophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Haematology: Monocytes	Change from baseline (week 0) in monocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Haematology: Lymphocytes	Change from baseline (week 0) in lymphocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.	Week 0, Week 26 and Week 52
Secondary	Change in Calcitonin	Reported results are number of subjects with low, normal or high calcitonin values at week 0, week 26 and week 52. Number of subjects analyzed = number of subjects contributed to the analysis for individual time point. Calcitonin values were categorised as low, normal or high.	Week 0 and Week 26 and Week 52

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