Efficacy and Safety of Liraglutide in Combination With Insulin Therapy Compared to Insulin Alone in Japanese Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

A 36-week, Randomised, Multi-centre, Double-blind, Parallel Group Trial to Investigate the Efficacy and Safety of Liraglutide in Combination With Insulin Therapy Compared to Insulin Monotherapy in Japanese Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01572740
• Other study ID #: NN2211-3925
• Secondary ID: U1111-1122-4320J
• Status: Completed
• Phase: Phase 3
• First received: April 4, 2012
• Last updated: January 11, 2018
• Start date: April 5, 2012
• Est. completion date: March 27, 2013

Study information

• Verified date: January 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 purpose of the trial is to investigate the efficacy and safety of liraglutide in combination with insulin therapy compared to insulin alone in Japanese subjects with type 2 diabetes mellitus. Subjects will remain on their pre-trial insulin therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 257
• Est. completion date: March 27, 2013
• Est. primary completion date: November 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Type 2 diabetes mellitus (diagnosed clinically) for at least 6 months

• Current insulin therapy (basal insulin, premixed insulin or basal-bolus regimen) in addition to diet and exercise therapy for at least 12 weeks prior to trial start. Their therapy is stable and fluctuation of total daily insulin dose is within plus/minus 20% for at least 12 weeks prior to trial start and current total daily insulin dose equal to or greater than 10 (I)U/day

• Glycosylated haemoglobin (HbA1c) between 7.5 and 11.0% (both inclusive)

• Body Mass Index (BMI) below 45.0 kg/m^2

Exclusion Criteria:

• Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as, but not limited to systemic corticosteroids, beta-antagonists or monoamine oxidase (MAO) inhibitors

• Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode during last 12 months) or hypoglycaemic unawareness as judged by the investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months

• Known proliferative retinopathy or maculopathy requiring treatment according to the investigator

• Treatment with glucagon-like peptide-1 (GLP-1) receptor agonist within 12 weeks prior to screening

• Treatment with any oral antidiabetic drugs (OADs) within 12 weeks prior to screening

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
Liraglutide administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.
• placebo
Liraglutide placebo administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.
• insulin
All subjects will continue their pre-trial insulin therapy (basal, premixed or basal-bolus regimen) during the trial. Insulin dose is fixed for the first 16 weeks and for the subsequent 20 weeks, insulin dose is individually adjusted.

Locations

Country	Name	City	State
Japan	Novo Nordisk Investigational Site	Chuo-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Ebina-shi
Japan	Novo Nordisk Investigational Site	Ebina-shi, Kanagawa
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Katsushika-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Koriyama-shi, Fukushima
Japan	Novo Nordisk Investigational Site	Miyazaki-shi
Japan	Novo Nordisk Investigational Site	Naka-shi, Ibaraki
Japan	Novo Nordisk Investigational Site	Niigata-shi, Niigata
Japan	Novo Nordisk Investigational Site	Nishinomiya-shi, Hygo
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	Ota-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Oyama-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Sendai-shi
Japan	Novo Nordisk Investigational Site	Shimotsuke-shi, Tochigi
Japan	Novo Nordisk Investigational Site	Shizuoka-shi
Japan	Novo Nordisk Investigational Site	Takatsuki-shi, Osaka
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Yokohama-shi

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Japan, 

References & Publications (2)

Kaneko S, Nishijima K, Bosch-Traberg H, Kaku K, Seino Y. Efficacy and safety of adding liraglutide to existing insulin regimens in Japanese patients with type 2 diabetes mellitus: A post-hoc analysis of a phase 3 randomized clinical trial. J Diabetes Inve — View Citation

Seino Y, Kaneko S, Fukuda S, Osonoi T, Shiraiwa T, Nishijima K, Bosch-Traberg H, Kaku K. Combination therapy with liraglutide and insulin in Japanese patients with type 2 diabetes: A 36-week, randomized, double-blind, parallel-group trial. J Diabetes Inve — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 16	Estimated mean change from baseline in HbA1c after 16 Weeks of treatment.	Week 0, Week 16
Secondary	Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 36	Estimated mean change from baseline in HbA1c after 36 Weeks of treatment	Week 0, Week 36
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16	Estimated mean change from baseline in FPG after 16 Weeks of treatment.	Week 0, Week 16
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 36	Estimated mean change from baseline in FPG after 36 Weeks of treatment.	Week 0, Week 36
Secondary	Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 16	Estimated mean change from baseline in mean PG of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 16 Weeks of treatment.	Week 0, Week 16
Secondary	Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 36	Estimated mean change from baseline in mean PG of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 36 Weeks of treatment.	Week 0, Week 36
Secondary	Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 16	Estimated mean change from baseline in mean prandial PG increment of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 16 Weeks of treatment.	Week 0, Week 16
Secondary	Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 36	Estimated mean change from baseline in mean prandial PG increment of 7-point profile (7-points were before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner and at bedtime) after 36 Weeks of treatment.	Week 0, Week 36
Secondary	Change in Body Weight From Baseline to Week 16	Estimated mean change in body weight after 16 Weeks of treatment	Week 0, Week 16
Secondary	Change in Body Weight From Baseline to Week 36	Estimated mean change in body weight after 36 Weeks of treatment	Week 0, Week 36
Secondary	Number of Adverse Events (AEs)	An AE was defined as treatment emergent if the onset date was on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.	Week 0 to Week 36 (inclusive)
Secondary	Number of Confirmed Hypoglycaemic Episodes	A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and until the last day on randomised treatment. Confirmed hypoglycaemic episode was defined as hypoglycaemic episodes categorised to severe and/or minor hypoglycaemic episodes.; Confirmed hypoglycaemia: subject unable to treat himself/herself and/or have a recorded PG < 3.1 mmol/L (56 mg/dL). Minor: PG < 3.1 mmol/L (56 mg/dL).	Week 0 to week 36 (inclusive)

External Links

•   Clinical Trials at Novo Nordisk