DiabetesPhase 3NCT01572740

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

A Phase 3 study testing liraglutide and insulin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 23 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 2
What is being tested?: liraglutide and insulin
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 257 participants
Where: 23 sitesJapan
Study dates: 5 Apr 2012to 27 Mar 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

23 sites in 1 country.

City, postcode or hospital

23 sites in 1 country

Japan23 sites

Novo Nordisk Investigational Site
Chuo-ku, Tokyo, 103 0002
Novo Nordisk Investigational Site
Ebina-shi, 243 0432
Novo Nordisk Investigational Site
Ebina-shi, Kanagawa, 243 0401
Novo Nordisk Investigational Site
Kashiwara-shi, Osaka, 582 0005
Novo Nordisk Investigational Site
Katsushika-ku, Tokyo, 125 0054
Novo Nordisk Investigational Site
Koriyama-shi, Fukushima, 963 8851
Novo Nordisk Investigational Site
Miyazaki, 880 0034
Novo Nordisk Investigational Site
Naka-shi, Ibaraki, 311 0113
Novo Nordisk Investigational Site
Niigata-shi, Niigata, 950 1104
Novo Nordisk Investigational Site
Nishinomiya-shi, Hygo, 662 0971
Novo Nordisk Investigational Site
Ōita, 870 0039
Novo Nordisk Investigational Site
Okawa-shi, Fukuoka, 831 0016
Novo Nordisk Investigational Site
Osaka-shi, Osaka, 553 0003
Novo Nordisk Investigational Site
Ota-ku, Tokyo, 144 0035
Novo Nordisk Investigational Site
Oyama-shi, Tochigi, 323 0022
Novo Nordisk Investigational Site
Sapporo-shi, Hokkaido, 060 0062
Novo Nordisk Investigational Site
Sapporo-shi, Hokkaido, 062 0007
Novo Nordisk Investigational Site
Sendai, 980 0021
Novo Nordisk Investigational Site
Shimotsuke-shi, Tochigi, 329 0433
Novo Nordisk Investigational Site
Shizuoka, 424 0853
Novo Nordisk Investigational Site
Takatsuki-shi, Osaka, 569 1096
Novo Nordisk Investigational Site
Tokyo, 187 8510
Novo Nordisk Investigational Site
Yokohama, 235 0045

Other trials in Japan

About this study

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

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: liraglutide, placebo, insulin
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

liraglutideDrug
Liraglutide administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.
placeboDrug
Liraglutide placebo administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.
insulinDrug
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.

Study groups in NCT01572740
Study group	Role	What they receive
Lira+Insulin	Experimental	Not described Receives: Drug: liraglutide; Drug: insulin
Placebo+Insulin	Placebo comparator	Not described Receives: Drug: placebo; Drug: insulin

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 16
Estimated mean change from baseline in HbA1c after 16 Weeks of treatment.
Measured: Week 0, Week 16

Secondary outcomes (11)

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 36
Estimated mean change from baseline in HbA1c after 36 Weeks of treatment
Measured: Week 0, Week 36
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16
Estimated mean change from baseline in FPG after 16 Weeks of treatment.
Measured: Week 0, Week 16
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 36
Estimated mean change from baseline in FPG after 36 Weeks of treatment.
Measured: Week 0, Week 36
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.
Measured: Week 0, Week 16
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.
Measured: Week 0, Week 36
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.
Measured: Week 0, Week 16
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.
Measured: Week 0, Week 36
Change in Body Weight From Baseline to Week 16
Estimated mean change in body weight after 16 Weeks of treatment
Measured: Week 0, Week 16
Change in Body Weight From Baseline to Week 36
Estimated mean change in body weight after 36 Weeks of treatment
Measured: Week 0, Week 36
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.
Measured: Week 0 to Week 36 (inclusive)
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).
Measured: Week 0 to week 36 (inclusive)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Apr 201227 Mar 2013

First posted6 Apr 2012 (estimated)
Study start5 Apr 2012
Primary completion1 Nov 2012
Study completion27 Mar 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 257 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01572740
Sponsor's protocol ID: NN2211-3925
Other IDs: U1111-1122-4320, JapicCTI-121802
Status last verified: Jan 2018
First submitted: 4 Apr 2012
Last updated: 7 Feb 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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 Investig. 2016 Jul;7(4):565-73. doi: 10.1111/jdi.12457. Epub 2016 Jan 23.
PubMed 27182042
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 Investig. 2018 Jul;9(4):840-849. doi: 10.1111/jdi.12793. Epub 2018 Feb 5.
PubMed 29277968

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01572740
Acronym / sponsor ID: NN2211-3925
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 257 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: 5 Apr 2012 (actual)
Primary completion: 1 Nov 2012 (actual)
Study completion: 27 Mar 2013 (actual)
First posted: 6 Apr 2012 (estimated)
Results: Posted 23 May 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Lira+Insulin	Experimental	Drug: liraglutide, Drug: insulin
Placebo+Insulin	Placebo comparator	Drug: placebo, Drug: insulin

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
liraglutideLiraglutide administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.	Drug	Lira+Insulin
placeboLiraglutide placebo administered subcutaneously (s.c., under the skin) for 36 weeks combined with insulin therapy.	Drug	Placebo+Insulin
insulinAll 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.	Drug	Lira+Insulin, Placebo+Insulin

Primary outcome

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 16
Time frame: Week 0, Week 16
Estimated mean change from baseline in HbA1c after 16 Weeks of treatment.

11 secondary outcomes

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 36
Time frame: Week 0, Week 36
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 16
Time frame: Week 0, Week 16
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 36
Time frame: Week 0, Week 36
Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 16
Time frame: Week 0, Week 16
Change in Mean Plasma Glucose (PG) of 7-Point Profile From Baseline to Week 36
Time frame: Week 0, Week 36
Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 16
Time frame: Week 0, Week 16
Change in Mean Prandial PG Increment of 7-Point Profile From Baseline to Week 36
Time frame: Week 0, Week 36
Change in Body Weight From Baseline to Week 16
Time frame: Week 0, Week 16
Change in Body Weight From Baseline to Week 36
Time frame: Week 0, Week 36
Number of Adverse Events (AEs)
Time frame: Week 0 to Week 36 (inclusive)
Number of Confirmed Hypoglycaemic Episodes
Time frame: Week 0 to week 36 (inclusive)

Results and safety

Results posted to the registry on 23 May 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lira + Insulin	127	121
Placebo + Insulin	130	125

Primary outcome: Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 16

Time frame: Week 0, Week 16. Mean (Standard Error). Unit: percentage of glycosylated haemoglobin

Measure	Lira + Insulin n = 127	Placebo + Insulin n = 129
Value	-1.73 (0.06)	-0.43 (0.06)

Lira + Insulin vs Placebo + Insulin: Estimated treatment difference, Mean: -1.30 (95% CI -1.47 to -1.13), p <0.0001, ANCOVA

Population analysed: Full analysis set (FAS) included all randomised subjects who received at least one dose of trial products. Missing data were imputed using last observation carried forward (LOCF). 1 subject in the placebo group did not contribute to the statistical analysis at Week 16 as subject was withdrawn from the trial before sampling for any efficacy data.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected in a timeframe of 36 weeks + 7 days follow up.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lira + Insulin	6 of 127 (4.7%)	93 of 127 (73.2%)	Not reported
Placebo + Insulin	4 of 130 (3.1%)	69 of 130 (53.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27182042Seino 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 Investig. 2016 Jul;7(4):565-73. doi: 10.1111/jdi.12457. Epub 2016 Jan 23.
Results publication: PubMed 29277968Kaneko 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 Investig. 2018 Jul;9(4):840-849. doi: 10.1111/jdi.12793. Epub 2018 Feb 5.
Clinical Trials at Novo NordiskLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

23 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing liraglutide and insulin in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 23 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 16 (time frame: Week 0, Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01572740, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2018.