UMIN-CTR Clinical Trial

Public title

Study about glucose and lipid metabolism of DPP-4 inhibitor versus ipragliflozin in inadequately controlled type 2 diabetes

Acronym

LEVELUP trial

Scientific Title

Study about glucose and lipid metabolism of DPP-4 inhibitor versus ipragliflozin in inadequately controlled type 2 diabetes

Scientific Title:Acronym

LEVELUP trial

Region

Japan

Condition

Type 2 diabetes

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the influence of DPP-4 inhibitor and ipragliflozin on serum glucose maintenance and lipid metabolisms in patients with type 2 diabetes inadequate glycemic control nevertheless diet or exercise therapy, or administrated oral antidiabetic agents except for DPP-4 inhibitor or SGLT-2 inihibitor at least 12 weeks.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Change in HbA1c from baseline to 52 weeks

Key secondary outcomes

Until changing of currently administered medication or addition of other medications at registration
Change and percent change in following items from baseline to 12, 24, 36 and 52 weeks
1) HbA1c (Except for 52 week)
2) Body weight
3) Waist circumference
4) Plasma glucose (Fasting or casual)
5) IRI (HOMA-IR, HOMA-beta)
6) Serum lipids: TC, TG, HDL-C, (LDL-C, non HDL-C)
(LDL-C is calculated by Friedewald equation, and if TG level is more than 400 mg/dL, it is treated as a reference value
7) Blood pressure (If measured at home, either those at home or those at examination room, whichever lower is adopted)
8) Leptin, adiponectin, glucagon, GIP, GLP-1
(Glucagon measurement is done at fasting. If the case of postprandial, time from last meal is recorded)
9) Serum ketone bodies
(Specific examination will be performed, if possible )
10) Analyzed stratified by patient characteristics such as duration of diabetes and concomitant drug

Study type

Interventional

Basic design

Parallel

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

DPP-4 inhibitor (Administered according to the package insert)

Interventions/Control_2

Orally administration of 50 mg ipragliflozin once a day, pre or post breakfast (Without DPP-4 inhibitor)

Interventions/Control_3

Orally administration of 50 mg ipragliflozin once a day, pre or post breakfast (With DPP-4 inhibitor)

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

80

years-old

>=

Gender

Male and Female

Key inclusion criteria

1) Provide written informed consent
2) Aged from 20 to 80 years at providing consent
3) At least 12 weeks after being diagnosed as type 2 diabetes at initiation
4) Patients who undergoes only diet/exercise therapy, or poorly glycemic controlled nevertheless who undergo hypoglycemic agent except for SGLT-2 inhibitor at least 12 weeks
5) HbA1c >=7.0% and <10.0%

[Inclusion criteria for DPP-4 inhibitor group]
6) Has less than 6 months medical history of DPP-4 inhibitor without any change in prescription at enrollment, and meet 1)-5) of inclusion criteria

[Inclusion criteria for ipragliflozin group]
7) Not administered DPP-4 inhibitors at enrollment, and meet 1)-5) of inclusion criteria

[Inclusion criteria for ipragliflozin and DPP-4 inhibitor concomitant in poorly glycemic controlled group]
8) Has at least 6 months medical history of DPP-4 inhibitor from enrollment, and meet 1)-5) of inclusion criteria

Key exclusion criteria

1) Type 1 diabetes
2) With severe ketosis, diabetic coma, or precoma
3) With severe infection, pre or post surgery, and serious trauma
4) Has history of hypersensitivity to study drugs
5) Renal dysfunction (Serum Creatinine male: >= 1.5 mg/dL, female: >= 1.3 mg/dL, eGFR < 30 ml/min/1.73m²)
6) With serious hepatic dysfunction
7) Has stroke, myocardial infarction, or other serious cardiovascular complications requiring hospitalization within 6 months at initiation
8) Is receiving SGLT-2 inhibitor, insulin, or GLP-1 agonist at initiation
9) Is pregnant, nursing, or planned to become pregnant
10) Considered as inadequate by the investigator

Target sample size

300

Name of lead principal investigator

1st name
Middle name
Last name	Nozomu Kamei

Organization

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Division name

Department of Endocrinology and Metabolism

Zip code

Address

1-9-6 Senda-machi, Naka-ku, Hiroshima, Japan

TEL

082-241-3111

Email

nozomu.kamei@gmail.com

Name of contact person

1st name
Middle name
Last name	Fumio Sawano

Organization

Sawano Thyroid and Diabetes Specialized Clinic

Division name

President

Zip code

Address

3-8-5, Ote-machi, Naka-ku, Hiroshima, Japan

TEL

082-545-1673

Homepage URL

Email

sawano-tdsc@citrus.ocn.ne.jp

Institute

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Institute

Department

Personal name

Organization

Astellas Pharma Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2014

Year

10

Month

08

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

A total of 101 patients with T2DM were divided into 3 groups [28 patients of DPP-4i monotherapy, 23 patients of Ipragliflozin monotherapy, or 50 patients of combination therapy of DPP-4i and Ipragliflozin] and were treated for 52 weeks.
HbA1c levels in all groups were significantly decreased after 52 weeks therapy compared to 0 week.
After 52 weeks therapy, fasting blood glucose level, body weight, and waist circumference were significantly decreased in Ipragliflozin monotherapy group and combination therapy group, and ketone body level showed an increasing trend in those groups. Levels of HOMA-IR, leptin, and high-molecular weight adiponectin showed a trend toward improvement in the combination therapy group.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

08

Month

13

Day

Date of IRB

Anticipated trial start date

2014

Year

10

Month

10

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2014

Year

10

Month

08

Day

Last modified on

2018

Year

03

Month

15

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017889