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.

Novo Nordisk A/S635 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

635

Conditions

Diabetes Diabetes Mellitus, Type 2

Interventions

liraglutideDRUG

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

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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

Locations (47)

Outcomes

Primary Outcomes

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.

Time frame: Week 0, Week 26

Secondary Outcomes

Change in HbA1c (Week 52)

Change from baseline (week 0) in HbA1c was evaluated after 52 weeks of treatment.

Time frame: Week 0, Week 52

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.

Time frame: Week 26 and Week 52

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.

Time frame: Week 26 and Week 52

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.

Time frame: Week 26 and Week 52

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'

Data from ClinicalTrials.gov

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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, Tokyo, Japan

Novo Nordisk Investigational Site

Chuo-ku, Tokyo, Japan

Novo Nordisk Investigational Site

Chūōku, 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

...and 37 more locations

Time frame: Week 26 and Week 52

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: 1. Before breakfast. 2. 90 minutes after start of breakfast. 3. Before lunch. 4. 90 minutes after start of lunch. 5. Before dinner. 6. 90 minutes after start of dinner. 7. At bedtime.

Time frame: Week 0 and Week 26 and Week 52

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.

Time frame: Week 0, Week 26, Week 52

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.

Time frame: Week 0, Week 26, Week 52

Change in Fasting Plasma Glucose (FPG)

Change from baseline (week 0) in FPG was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Waist Circumference

Change from baseline (week 0) in waist circumference was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Body Weight

Change from baseline (week 0) in body weight was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Body Mass Index (BMI)

Change from baseline (week 0) in BMI was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

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.

Time frame: Week 0, Week 26, Week 52

Fasting C-peptide

Fasting C-peptide was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Fasting Insulin

Fasting insulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Fasting Glucagon

Fasting glucagon was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Proinsulin

Proinsulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Proinsulin/Insulin

Proinsulin/insulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

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=\[(20 x fasting insulin in µU/mL)/(FPG in mmol/L-3.5)\].

Time frame: Week 26 and Week 52

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.

Time frame: Week 26 and Week 52

Total Cholesterol

Total cholesterol was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Low Density Lipoprotein (LDL) Cholesterol

LDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

High Density Lipoprotein (HDL) Cholesterol

HDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Very Low Density Lipoprotein (VLDL) Cholesterol

VLDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Triglycerides

Triglycerides were evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

Free Fatty Acids

Free fatty acids were evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 26 and Week 52

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'.

Time frame: Weeks 0-26 and Weeks 0-52

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'.

Time frame: Weeks 0-26 and Weeks 0-52

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'.

Time frame: Weeks 0-26 and Weeks 0-52

Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition

American Diabetes Association (ADA) classification of hypoglycaemia: 1. 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. 2. Documented symptomatic: PG level ≤3.9 mmol/L with symptoms. 3. Asymptomatic: PG level ≤3.9 mmol/L without symptoms. 4. Probable symptomatic: No measurement with symptoms. 5. 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'.

Time frame: Weeks 0-26 and Weeks 0-52

Change in Pulse

Change from baseline (week 0) in pulse was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

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). 1. Cardiovascular system 2. Central and peripheral nervous system (PNS) 3. Gastrointestinal (GI) system including mouth 4. General appearance 5. Head, ears, eyes, nose, throat, neck 6. Lymph node palpation 7. Musculoskeletal system 8. Respiratory system 9. Skin 10. Thyroid gland

Time frame: Week 0 and Week 26 and Week 52

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.

Time frame: Week 0 and Week 26 and Week 52

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.

Time frame: Week 0 and Week 26 and Week 52

Change in Biochemistry: Creatinine

Change from baseline (week 0) in creatinine was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

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.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Alanine Aminotransferase

Change from baseline (week 0) in alanine aminotransferase was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Aspartate Aminotransferase

Change from baseline (week 0) in aspartate aminotransferase was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Alkaline Phosphatase

Change from baseline (week 0) in alkaline phosphatase was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Sodium

Change from baseline (week 0) in sodium was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Potassium

Change from baseline (week 0) in potassium was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Albumin

Change from baseline (week 0) in albumin was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Total Bilirubin

Change from baseline (week 0) in total bilirubin was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Urea

Change from baseline (week 0) in urea was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Creatine Kinase

Change from baseline (week 0) in creatine kinase was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Calcium

Change from baseline (week 0) in calcium was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

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.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Amylase

Change from baseline (week 0) in amylase was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Biochemistry: Lipase

Change from baseline (week 0) in lipase was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

Change in Haematology: Haemoglobin

Change from baseline (week 0) in haemoglobin was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26, Week 52

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.

Time frame: Week 0, Week 26, Week 52

Change in Haematology: Thrombocytes

Change from baseline (week 0) in thrombocytes (platelets) was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

Change in Haematology: Erythrocytes

Change from baseline (week 0) in erythrocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

Change in Haematology: Leukocytes

Change from baseline (week 0) in leukocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

Change in Haematology: Eosinophils

Change from baseline (week 0) in eosinophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

Change in Haematology: Neutrophils

Change from baseline (week 0) in neutrophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

Change in Haematology: Basophils

Change from baseline (week 0) in basophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

Change in Haematology: Monocytes

Change from baseline (week 0) in monocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

Change in Haematology: Lymphocytes

Change from baseline (week 0) in lymphocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.

Time frame: Week 0, Week 26 and Week 52

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.

Time frame: Week 0 and Week 26 and Week 52