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.
- Registration Number
- NCT02505334
- Lead Sponsor
- Novo Nordisk A/S
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 635
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Liraglutide 1.8 mg liraglutide The total trial duration for the 1.8 mg/day treatment arm will be approximately 67 weeks, consisting of 2 weeks screening period, a 12 weeks run-in period, a 26-week main treatment period, a safety extension period of 26 weeks and a follow-up visit. Liraglutide 0.9 mg liraglutide The total trial duration for the 0.9 mg/day treatment arm will be approximately 41 weeks, consisting of 2 weeks screening period, a 12 weeks run-in period, a 26-week treatment period, and a follow-up visit.
- Primary Outcome Measures
Name Time Method Change in Glycosylated Haemoglobin (HbA1c) (Week 26) Week 0, 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.
- Secondary Outcome Measures
Name Time Method Change in HbA1c (Week 52) Week 0, Week 52 Change from baseline (week 0) in HbA1c was evaluated after 52 weeks of treatment.
Responder for HbA1c Below 7.0% (53 mmol/Mol) Week 26 and Week 52 Reported results are number of subjects who achieved HbA1c target below 7.0% after 26 weeks and 52 weeks of treatment, respectively.
Responder for HbA1c Below or Equal to 6.5% (48 mmol/Mol) Week 26 and Week 52 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.
Responder for HbA1c Below 7.0% Without Weight Gain Week 26 and Week 52 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.
Change in Self-Measured Blood Glucose (SMBG) 7-point Profile: 7-point Profile (Individual Points in the Profile) Week 0 and Week 26 and Week 52 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.Responder for HbA1c Below 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes Week 26 and Week 52 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'
Change in SMBG 7-point Profile: Mean of 7-point Profile Week 0, Week 26, Week 52 Change from baseline (week 0) in mean of the SMBG 7-point profile was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in SMBG 7-point Profile: Mean of Postprandial Increments (From Before Meal to 90 Minutes After for Breakfast, Lunch and Dinner) Week 0, Week 26, Week 52 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.
Change in Fasting Plasma Glucose (FPG) Week 0, Week 26, Week 52 Change from baseline (week 0) in FPG was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Waist Circumference Week 0, Week 26, Week 52 Change from baseline (week 0) in waist circumference was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Body Weight Week 0, Week 26, Week 52 Change from baseline (week 0) in body weight was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Body Mass Index (BMI) Week 0, Week 26, Week 52 Change from baseline (week 0) in BMI was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Blood Pressure (Systolic and Diastolic) Week 0, Week 26, Week 52 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.
Fasting C-peptide Week 26 and Week 52 Fasting C-peptide was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Fasting Insulin Week 26 and Week 52 Fasting insulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Fasting Glucagon Week 26 and Week 52 Fasting glucagon was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Proinsulin Week 26 and Week 52 Proinsulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Proinsulin/Insulin Week 26 and Week 52 Proinsulin/insulin was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Albumin Corrected Calcium Week 0, Week 26, Week 52 Change from baseline (week 0) in albumin corrected calcium was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Homeostasis Model Assessment of Beta-cell Function (HOMA-B) Week 26 and Week 52 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=\[(20 x fasting insulin in µU/mL)/(FPG in mmol/L-3.5)\].
Homeostasis Model Assessment as an Index of Insulin Resistance (HOMA-IR) Week 26 and Week 52 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.
Total Cholesterol Week 26 and Week 52 Total cholesterol was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Low Density Lipoprotein (LDL) Cholesterol Week 26 and Week 52 LDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.
High Density Lipoprotein (HDL) Cholesterol Week 26 and Week 52 HDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Very Low Density Lipoprotein (VLDL) Cholesterol Week 26 and Week 52 VLDL was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Triglycerides Week 26 and Week 52 Triglycerides were evaluated after 26 weeks and 52 weeks of treatment, respectively.
Free Fatty Acids Week 26 and Week 52 Free fatty acids were evaluated after 26 weeks and 52 weeks of treatment, respectively.
Number of Treatment Emergent Adverse Events Weeks 0-26 and Weeks 0-52 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'.
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 0-26 and Weeks 0-52 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'.
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 0-26 and Weeks 0-52 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'.
Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition Weeks 0-26 and Weeks 0-52 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'.Change in Pulse Week 0, Week 26, Week 52 Change from baseline (week 0) in pulse was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Physical Examination Week 0 and Week 26 and Week 52 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 glandChange in Eye Examination Week 0 and Week 26 and Week 52 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.
Change in Electrocardiogram (ECG) Week 0 and Week 26 and Week 52 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.
Change in Biochemistry: Creatinine Week 0, Week 26, Week 52 Change from baseline (week 0) in creatinine was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: eGFR Week 0, Week 26, Week 52 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.
Change in Biochemistry: Alanine Aminotransferase Week 0, Week 26, Week 52 Change from baseline (week 0) in alanine aminotransferase was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Aspartate Aminotransferase Week 0, Week 26, Week 52 Change from baseline (week 0) in aspartate aminotransferase was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Alkaline Phosphatase Week 0, Week 26, Week 52 Change from baseline (week 0) in alkaline phosphatase was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Sodium Week 0, Week 26, Week 52 Change from baseline (week 0) in sodium was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Potassium Week 0, Week 26, Week 52 Change from baseline (week 0) in potassium was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Albumin Week 0, Week 26, Week 52 Change from baseline (week 0) in albumin was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Total Bilirubin Week 0, Week 26, Week 52 Change from baseline (week 0) in total bilirubin was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Urea Week 0, Week 26, Week 52 Change from baseline (week 0) in urea was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Creatine Kinase Week 0, Week 26, Week 52 Change from baseline (week 0) in creatine kinase was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Calcium Week 0, Week 26, Week 52 Change from baseline (week 0) in calcium was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Amylase Week 0, Week 26, Week 52 Change from baseline (week 0) in amylase was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Biochemistry: Lipase Week 0, Week 26, Week 52 Change from baseline (week 0) in lipase was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Haemoglobin Week 0, Week 26, Week 52 Change from baseline (week 0) in haemoglobin was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Haematocrit Week 0, Week 26, Week 52 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.
Change in Haematology: Thrombocytes Week 0, Week 26 and Week 52 Change from baseline (week 0) in thrombocytes (platelets) was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Erythrocytes Week 0, Week 26 and Week 52 Change from baseline (week 0) in erythrocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Leukocytes Week 0, Week 26 and Week 52 Change from baseline (week 0) in leukocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Basophils Week 0, Week 26 and Week 52 Change from baseline (week 0) in basophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Monocytes Week 0, Week 26 and Week 52 Change from baseline (week 0) in monocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Lymphocytes Week 0, Week 26 and Week 52 Change from baseline (week 0) in lymphocytes was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Calcitonin Week 0 and Week 26 and Week 52 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.
Change in Haematology: Eosinophils Week 0, Week 26 and Week 52 Change from baseline (week 0) in eosinophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Change in Haematology: Neutrophils Week 0, Week 26 and Week 52 Change from baseline (week 0) in neutrophils was evaluated after 26 weeks and 52 weeks of treatment, respectively.
Trial Locations
- Locations (1)
Novo Nordisk Investigational Site
🇯🇵Yokohama-shi, Japan