DiabetesPhase 3NCT01512108

Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Alone

A Phase 3 study testing liraglutide and oral anti-diabetic drug in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 36 sites in Japan.

Completed

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

Official record

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Trial summary

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 oral anti-diabetic drug
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 363 participants
Where: 36 sitesJapan
Study dates: 10 Jan 2012to 26 Apr 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

Informed consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject.)
Japanese subjects with type 2 diabetes on monotherapy with an OAD (either glinide, metformin, a-glucosidase inhibitor or thiazolidinedione) within approved Japanese labelling in addition to diet and exercise therapy. Total daily dose and type of drug should have remained unchanged for at least 8 weeks prior to Visit 1
Type 2 diabetes mellitus (clinically diagnosed) for at least 6 months
HbA1c between 7.0-10.0% (both inclusive)
Body Mass Index (BMI) below 40.0 kg/m^2
Outpatients who have no plans for an educational hospitalisation for the purpose of glycaemic control. However, hospitalisation for training of self-injection from Visit 2 that is for no longer than one week is allowed
Subjects able and willing to perform self-monitoring of plasma glucose (SMPG)

Who cannot join

Subjects with known or previous malignant tumor and are strongly suspected of recurrence (except basal cell skin cancer or squamous cell skin cancer)
Calcitonin above or equal to 160 pg/mL
Personal history of non-familial medullary thyroid carcinoma
Family or personal history of multiple endocrine neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma (FMTC)
History of chronic pancreatitis or idiopathic acute pancreatitis
Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
Treatment with GLP-1 receptor agonist or dipeptidyl peptidase 4 (DPP-4) inhibitor within 12 weeks prior to Visit 1
Having contraindications to liraglutide and any of the OADs (according to Japanese labelling)

Trial locations and contacts

36 sites in 1 country.

City, postcode or hospital

36 sites in 1 country

Japan36 sites

Novo Nordisk Investigational Site
Chuo-ku, Tokyo, 103 0002
Novo Nordisk Investigational Site
Chuo-ku, Tokyo, 103 0027
Novo Nordisk Investigational Site
Ehime, Japan, 790 0067
Novo Nordisk Investigational Site
Fukuoka, 812 0025
Novo Nordisk Investigational Site
Fukuoka, 818 8502
Novo Nordisk Investigational Site
Fukuoka, 820 8505
Novo Nordisk Investigational Site
Fukuoka-shi, Fukuoka, 815 8555
Novo Nordisk Investigational Site
Fukuoka, Japan, 810 8798
Novo Nordisk Investigational Site
Kamagaya-shi, Chiba, 273 0121
Novo Nordisk Investigational Site
Kashiwara-shi, Osaka, 582 0005
Novo Nordisk Investigational Site
Kawagoe-shi, Saitama, 350 0851
Novo Nordisk Investigational Site
Kitakyushu-shi, Fukuoka, 800 0252
Novo Nordisk Investigational Site
Koriyama-shi, Fukushima, 963 8851
Novo Nordisk Investigational Site
Kumamoto-shi,Kumamoto, 862 0976
Novo Nordisk Investigational Site
Kurume-shi, Fukuoka, 839 0863
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
Ōita, 870 8511
Novo Nordisk Investigational Site
Okawa-shi, Fukuoka, 831 0016
Novo Nordisk Investigational Site
Osaka-shi, Osaka, 532 0003
Novo Nordisk Investigational Site
Osaka-shi, Osaka, 545 8586
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, 060-0001
Novo Nordisk Investigational Site
Sapporo-shi, Hokkaido, 062 0007
Novo Nordisk Investigational Site
Shimotsuke-shi, Tochigi, 329 0433
Novo Nordisk Investigational Site
Shizuoka, 424 0853
Novo Nordisk Investigational Site
Tagajō-shi, 985 0852
Novo Nordisk Investigational Site
Takatsuki-shi, Osaka, 569 1096
Novo Nordisk Investigational Site
Tochigi, 329 0498
Novo Nordisk Investigational Site
Tokyo, 104 0044
Novo Nordisk Investigational Site
Tokyo, 113 0031
Novo Nordisk Investigational Site
Tokyo, 125 0054
Novo Nordisk Investigational Site
Yamaguchi, 755 0067
Novo Nordisk Investigational Site
Yokohama, 235 0045

Other trials in Japan

About this study

Official title: A 52-week, Multi-centre, Open-labelled, Randomised (2:1), Parallel-group Trial With an Active Control (Two OADs Combination Therapy) to Evaluate the Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Monotherapy

This trial was conducted in Japan. The aim of this trial was to evaluate the safety and efficacy of once daily administration of liraglutide in combination with an oral anti-diabetic drug (OAD) in Japanese subjects with type 2 diabetes who are insufficiently controlled on OAD monotherapy. All subjects will continue their pre-trial OAD (either glinide, metformin, alpha-glucosidase inhibitor or thiazolidinedione) during the trial at unchanged type and dose.

Conditions: Diabetes, Diabetes Mellitus, Type 2
Being tested: liraglutide, oral anti-diabetic drug
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
0.9 mg/day liraglutide was injected once daily subcutaneously (s.c., under the skin).
oral anti-diabetic drugDrug
An additional oral anti-diabetic drug (OAD) with a different mechanism of action than the pre-trial OAD. The type and dosage of the additional OAD should be chosen by the investigator within the Japanese labelled dose.

Study groups in NCT01512108
Study group	Role	What they receive
Liraglutide + an OAD therapy	Experimental	Not described Receives: Drug: liraglutide
Two OADs combination therapy	Active comparator	Not described Receives: Drug: oral anti-diabetic drug

What is being measured

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

Incidence of Treatment Emergent Adverse Events (AEs)
Adverse events were defined as events occurring after administration of trial product and no later than 7 days after last day of treatment. Severe AEs: considerable interference with subject's daily activities. Moderate AEs: Marked symptoms, moderate interference with the subject's daily activities. Mild AEs: No or transient symptoms, no interference with the subject's daily activities. Serious AEs: AEs that resulted in any of the following: death, a life-threatening experience, hospitalization/prolongation of existing hospitalization, persistent/significant disability, and congenital anomaly.
Measured: Week 0 to Week 52 + 7 days

Secondary outcomes (3)

Number of Confirmed Hypoglycaemic Episodes
Confirmed hypoglycaemic episodes consisted of the pool of episodes of severe hypoglycaemia as well as minor hypoglycaemic episodes [An episode with symptoms consistent with hypoglycaemia with confirmation by plasma glucose <3.1 mmol/L (56 mg/dL) or full blood glucose <2.8 mmol/L (50 mg/dL) and which is handled by the subject himself or herself or any asymptomatic PG value <3.1 mmol/L (56 mg/dL) or full blood glucose value <2.8 mmol/L (50 mg/dL)] with a confirmed plasma glucose value of less than 3.1 mmol/L (56 mg/dL).
Measured: Week 0 to Week 52
Change in HbA1c From Baseline to Week 52
Estimated mean change in HbA1c from baseline after 52 Weeks of treatment
Measured: Week 0, week 52
Change in FPG From Baseline to Week 52
Estimated mean change from baseline in FPG after 52 Weeks of treatment
Measured: Week 0, week 52

Timeline

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

10 Jan 201226 Apr 2013

First posted19 Jan 2012 (estimated)
Study start10 Jan 2012
Primary completion26 Apr 2013
Study completion26 Apr 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: None (open label)
Enrolment: 363 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01512108
Sponsor's protocol ID: NN2211-3924
Other IDs: U1111-1121-3457, JapicCTI-121744
Status last verified: Nov 2017
First submitted: 10 Jan 2012
Last updated: 18 Dec 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Kaku K, Kiyosue A, Ono Y, Shiraiwa T, Kaneko S, Nishijima K, Bosch-Traberg H, Seino Y. Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: A randomized, 52-week, open-label, parallel-group trial. J Diabetes Investig. 2016 Jan;7(1):76-84. doi: 10.1111/jdi.12367. Epub 2015 Jul 14.
PubMed 26816604
Kiyosue A, Seino Y, Nishijima K, Bosch-Traberg H, Kaku K. Safety and efficacy of the combination of the glucagon-like peptide-1 receptor agonist liraglutide with an oral antidiabetic drug in Japanese patients with type 2 diabetes: Post-hoc analysis of a randomized, 52-week, open-label, parallel-group trial. J Diabetes Investig. 2018 Jul;9(4):831-839. doi: 10.1111/jdi.12759. Epub 2017 Nov 24.
PubMed 28984041

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 18 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 52-week, Multi-centre, Open-labelled, Randomised (2:1), Parallel-group Trial With an Active Control (Two OADs Combination Therapy) to Evaluate the Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Monotherapy
ClinicalTrials.gov ID: NCT01512108
Acronym / sponsor ID: NN2211-3924
Conditions: Diabetes, Diabetes Mellitus, Type 2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 363 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: 10 Jan 2012 (actual)
Primary completion: 26 Apr 2013 (actual)
Study completion: 26 Apr 2013 (actual)
First posted: 19 Jan 2012 (estimated)
Results: Posted 28 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: None (open label)
Number of arms: 2

Arm	Type	Receives
Liraglutide + an OAD therapy	Experimental	Drug: liraglutide
Two OADs combination therapy	Active comparator	Drug: oral anti-diabetic drug

Who may qualify

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

Key inclusion criteria (7 listed)

Informed consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject.)
Japanese subjects with type 2 diabetes on monotherapy with an OAD (either glinide, metformin, a-glucosidase inhibitor or thiazolidinedione) within approved Japanese labelling in addition to diet and exercise therapy. Total daily dose and type of drug should have remained unchanged for at least 8 weeks prior to Visit 1
Type 2 diabetes mellitus (clinically diagnosed) for at least 6 months
HbA1c between 7.0-10.0% (both inclusive)
Body Mass Index (BMI) below 40.0 kg/m^2

Key exclusion criteria (8 listed)

Subjects with known or previous malignant tumor and are strongly suspected of recurrence (except basal cell skin cancer or squamous cell skin cancer)
Calcitonin above or equal to 160 pg/mL
Personal history of non-familial medullary thyroid carcinoma
Family or personal history of multiple endocrine neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma (FMTC)
History of chronic pancreatitis or idiopathic acute pancreatitis

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
liraglutide0.9 mg/day liraglutide was injected once daily subcutaneously (s.c., under the skin).	Drug	Liraglutide + an OAD therapy
oral anti-diabetic drugAn additional oral anti-diabetic drug (OAD) with a different mechanism of action than the pre-trial OAD. The type and dosage of the additional OAD should be chosen by the investigator within the Japanese labelled dose.	Drug	Two OADs combination therapy

Primary outcome

Incidence of Treatment Emergent Adverse Events (AEs)
Time frame: Week 0 to Week 52 + 7 days
Adverse events were defined as events occurring after administration of trial product and no later than 7 days after last day of treatment. Severe AEs: considerable interference with subject's daily activities. Moderate AEs: Marked symptoms, moderate interference with the subject's daily activities. Mild AEs: No or transient symptoms, no interference with the subject's daily activities. Serious AEs: AEs that resulted in any of the following: death, a life-threatening experience, hospitalization/prolongation of existing hospitalization, persistent/significant disability, and congenital anomaly.

3 secondary outcomes

Number of Confirmed Hypoglycaemic Episodes
Time frame: Week 0 to Week 52
Change in HbA1c From Baseline to Week 52
Time frame: Week 0, week 52
Change in FPG From Baseline to Week 52
Time frame: Week 0, week 52

Results and safety

Results posted to the registry on 28 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
Liraglutide 0.9 mg/Day	243	221
Additional OAD	120	111

Primary outcome: Incidence of Treatment Emergent Adverse Events (AEs)

Time frame: Week 0 to Week 52 + 7 days. Number. Unit: Events/100 years of patient exposure

Measure	Liraglutide 0.9 mg/Day n = 240	Additional OAD n = 120
All AEs	361	331
Mild AEs	345	321
Moderate AEs	14	9
Severe AEs	2	2
Serious AEs	5	9

Population analysed: Safety analysis set included all subjects who received at least one dose of the trial product.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were captured from the time of consent until 52 weeks of treatment and if needed were followed up after the final visit.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Liraglutide 0.9 mg/Day	11 of 240 (4.6%)	161 of 240 (67.1%)	Not reported
Additional OAD	10 of 120 (8.3%)	77 of 120 (64.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26816604Kaku K, Kiyosue A, Ono Y, Shiraiwa T, Kaneko S, Nishijima K, Bosch-Traberg H, Seino Y. Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: A randomized, 52-week, open-label, parallel-group trial. J Diabetes Investig. 2016 Jan;7(1):76-84. doi: 10.1111/jdi.12367. Epub 2015 Jul 14.
Results publication: PubMed 28984041Kiyosue A, Seino Y, Nishijima K, Bosch-Traberg H, Kaku K. Safety and efficacy of the combination of the glucagon-like peptide-1 receptor agonist liraglutide with an oral antidiabetic drug in Japanese patients with type 2 diabetes: Post-hoc analysis of a randomized, 52-week, open-label, parallel-group trial. J Diabetes Investig. 2018 Jul;9(4):831-839. doi: 10.1111/jdi.12759. Epub 2017 Nov 24.
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

36 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 oral anti-diabetic drug in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 36 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 7 inclusion and 8 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 18 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 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. 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 28 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?

Incidence of Treatment Emergent Adverse Events (AEs) (time frame: Week 0 to Week 52 + 7 days). 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 NCT01512108, 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 18 Dec 2017.