Type 2 Diabetes MellitusPhase 4NCT01449747

Pharmacokinetics Study of Dipeptidyl Peptidase 4 Inhibitor to Control Type 2 Diabetes Mellitus

A Phase 4 study testing Sitagliptin in people with Type 2 Diabetes Mellitus, run by The Catholic University of Korea at 2 sites in South Korea.

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

The purpose of this study is to confirm the mechanism of reduced response to DPP-4 inhibitor in some patients with type 2 diabetes and evaluate appropriate patients to treat with DPP-4 inhibitor Read more about this study

Who is it for?: Ages 20 to 70 years
Conditions the study is for: Type 2 Diabetes Mellitus
What is being tested?: Sitagliptin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 24 participants
Where: 2 sitesSouth Korea
Study dates: Dec 2011to Jul 2015
Phase: Phase 4
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 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Type 2 diabetic patients with less than 15 yrs of disease duration
BMI between 22-27 kg/m2
HbA1c ≤ 9% at recruitment
Study group
After change sulfonylurea to sitagliptin in case of metformin and sulfonylurea therapy
Increase of fasting blood glucose over 20 mg/dL or postprandial glucose over 30 mg/dL within several days or

Show all 13Show fewer

Increase of HbA1c over 1% within 2-3 months without abrupt increase of blood glucose levels within several days
Sulfonylurea dose : less than glimepiride 4mg or gliclazide 120mg or glibenclamide 10mg
Metformin dose : 500~2000mg
Reduced response to sitagliptin should be made a decision by investigators after understanding the condition of patients surely.
2. Control group
Age, sex, BMI matched patients with same condition of study patients
After change sulfonylurea to sitagliptin in case of metformin plus sulfonylurea therapy, no change of blood glucose levels like above or stable HbA1c change within 1% within 2-3 months

Who cannot join

Other causes of increase of blood glucose levels except drug change
Patients with history of insulin treatment
Patients taking thiazolidinediones, alpha-glucosidase inhibitors, GLP-1 analogue or DPP-4 inhibitors
Patients with renal, hepatic dysfunction
Patients with diabetic complications such as coronary heart disease, cerebrovascular disease, proliferative diabetic retinopathy or diabetic gastroparesis
Patients taking medications affecting glucose level

Trial locations and contacts

2 sites in 1 country.

South Korea2 sites

The Catholic University of Korea; St.Paul's Hospital
Seoul, 130-709
The Catholic University of Korea; Seoul St. Mary's Hospital
Seoul, 137-701

Other trials in South Korea

About this study

Official title: Mechanism of Reduced Response to DPP-4 Inhibitor in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to confirm the mechanism of reduced response to DPP-4 inhibitor in some patients with type 2 diabetes and evaluate appropriate patients to treat with DPP-4 inhibitor

Read the detailed description

Sitagliptin, a DPP-4 inhibitor was used as an incretin enhancer in clinical practice first. In clinical trials, sitagliptin showed effective control of blood glucose level in type 2 diabetes and 100 mg once daily with metformin was similar to sulfonylurea (glipizide) with metformin in lowering HbA1c. Mostly in practice, stable blood glucose levels were maintained after change of sulfonylurea to sitagliptin in type 2 diabetes treatment. However, in some cases, there were abrupt severe hyperglycemia and uncontrolled blood glucose level after drug change to sitagliptin.

Several mechanism could be considered for reduced response to DPP-4 inhibitor in some type 2 diabetes patients. Firstly, significantly reduced secretion of glucagon-like peptide 1 (GLP-1) more than expected in diabetes or functional defect of GLP-1 activity could be the mechanism of loss of GLP-1 effect irrespective of DPP-4. Secondly, mutation or functional defect of DPP-4 enzyme could not be inhibited by DPP-4 inhibitor. Thirdly, GLP-1 receptor mutation or other defect in β-cell responsiveness to GLP-1 leads to reduction of response to DPP-4 inhibitor.

Conditions: Type 2 Diabetes Mellitus
Being tested: Sitagliptin
Keywords: Type 2 diabetes mellitus, Dipeptidyl peptidase IV inhibitors, Glucagon-like peptide 1
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

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

SitagliptinDrug
Also called Januvia
Sitagliptin (100mg, per oral) once a day.

Study groups in NCT01449747
Study group	Role	What they receive
study group	Active comparator	sitagliptin hypo-response patients Receives: Drug: Sitagliptin
control group	Sham comparator	sitagliptin response patients Receives: Drug: Sitagliptin

What is being measured

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

Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment
Plasma concentrations of active GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test (MTT). Second measurement of active GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Measured: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment
Plasma concentrations of total GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Measured: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment
Plasma concentrations of total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GIP were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Measured: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment
Plasma concentrations of active GLP-1, total GLP-1 and total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurements were measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Comparisons were made using Area under the curve (AUC) values and incremental area under the curve (ΔAUC) of active GLP-1, total GLP-1 and total GIP before and after the addition of sitagliptin.
Measured: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose

Secondary outcomes (1)

Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups
The DPP-4 activity was measured at baseline and 0, 15, 30, 45 and 60 min during the meal tolerance test. Second measurement of DPP-4 activity was measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Plasma DPP-4 activity during meal tolerance test is expressed as percentage activity relative to baseline. DPP-4 activity % was calculated using the following formula : (DPP-4 activity at time t / Baseline DPP-4 activity) × 100.
Measured: 0, 15, 30, 45, 60 min post-dose

Timeline

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

Dec 2011Jul 2015

First posted10 Oct 2011 (estimated)
Study startDec 2011
Primary completionAug 2014
Study completionJul 2015

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.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
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 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01449747
Sponsor's protocol ID: CMCENDO-01
Status last verified: Nov 2015
First submitted: 29 Sep 2011
Last updated: 14 Dec 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Mechanism of Reduced Response to DPP-4 Inhibitor in Patients With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT01449747
Acronym / sponsor ID: CMCENDO-01
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 diabetes mellitus, Dipeptidyl peptidase IV inhibitors, Glucagon-like peptide 1
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: The Catholic University of KoreaUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: Dec 2011
Primary completion: Aug 2014 (actual)
Study completion: Jul 2015 (actual)
First posted: 10 Oct 2011 (estimated)
Results: Posted 14 Dec 2015

Clinical summary

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

The purpose of this study is to confirm the mechanism of reduced response to DPP-4 inhibitor in some patients with type 2 diabetes and evaluate appropriate patients to treat with DPP-4 inhibitor

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
study group	Active comparator	Drug: Sitagliptinsitagliptin hypo-response patients
control group	Sham comparator	Drug: Sitagliptinsitagliptin response patients

Who may qualify

Ages: 20 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Type 2 diabetic patients with less than 15 yrs of disease duration
BMI between 22-27 kg/m2
HbA1c ≤ 9% at recruitment
After change sulfonylurea to sitagliptin in case of metformin and sulfonylurea therapy
Increase of fasting blood glucose over 20 mg/dL or postprandial glucose over 30 mg/dL within several days or

Key exclusion criteria (6 listed)

Other causes of increase of blood glucose levels except drug change
Patients with history of insulin treatment
Patients taking thiazolidinediones, alpha-glucosidase inhibitors, GLP-1 analogue or DPP-4 inhibitors
Patients with renal, hepatic dysfunction
Patients with diabetic complications such as coronary heart disease, cerebrovascular disease, proliferative diabetic retinopathy or diabetic gastroparesis

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
SitagliptinAlso: JanuviaSitagliptin (100mg, per oral) once a day.	Drug	control group, study group

Primary outcome

Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of active GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test (MTT). Second measurement of active GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of total GLP-1 were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GLP-1 were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurement of total GIP were measured with MTT after taking sitagliptin 100 mg 1 hour before the test.
Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment
Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose
Plasma concentrations of active GLP-1, total GLP-1 and total GIP were measured at 0, 15, 30, 45, 60, 90, 120 and 180 min during the meal tolerance test. Second measurements were measured with MTT after taking sitagliptin 100 mg 1 hour before the test. Comparisons were made using Area under the curve (AUC) values and incremental area under the curve (ΔAUC) of active GLP-1, total GLP-1 and total GIP before and after the addition of sitagliptin.

1 secondary outcome

Differences of DPP-4 Activity After Sitagliptin Treatment Between Responder and Non-responder Groups
Time frame: 0, 15, 30, 45, 60 min post-dose

Results and safety

Results posted to the registry on 14 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Non-responder	12	12
Responder	12	12

Primary outcome: Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment

Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose. Mean (Standard Deviation). Unit: pmol/L

Measure	Non-responder n = 12	Responder n = 12
baseline 0 min	7.0 (6.6)	6.1 (1.9)
baseline 15 min	10.6 (8.0)	14.1 (24.4)
baseline 30 min	15.7 (10.3)	14.3 (20.2)
baseline 45 min	14.7 (8.2)	9.3 (4.3)
baseline 60 min	13.7 (6.8)	8.4 (2.7)
baseline 90 min	10.6 (5.4)	7.6 (2.1)
baseline 120 min	11.3 (6.8)	7.4 (2.1)
baseline 180 min	12.6 (8.7)	7.1 (2.5)

Primary outcome: Plasma Concentration of Total GLP-1 Before and After Sitagliptin Treatment

Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose. Mean (Standard Deviation). Unit: pmol/L

Measure	Non-responder n = 12	Responder n = 12
baseline 0 min	25.6 (26.9)	15.6 (16.2)
baseline 15 min	30.5 (26.1)	20.4 (19.7)
baseline 30 min	36.2 (26.8)	22.4 (17.0)
baseline 45 min	30.9 (18.9)	25.5 (21.0)
baseline 60 min	31.8 (20.9)	21.7 (19.9)
baseline 90 min	31.8 (24.3)	19.2 (17.1)
baseline 120 min	31.3 (22.2)	19.9 (18.0)
baseline 180 min	34.5 (28.3)	19.3 (17.5)

Primary outcome: Plasma Concentration of Total Glucose-dependent Insulinotropic Polypeptide (GIP) Before and After Sitagliptin Treatment

Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose. Mean (Standard Deviation). Unit: pmol/L

Measure	Non-responder n = 12	Responder n = 12
baseline 0 min	13.8 (4.5)	12.3 (6.9)
baseline 15 min	42.3 (30.7)	40.3 (28.1)
baseline 30 min	109.6 (49.9)	60.2 (39.8)
baseline 45 min	109.6 (43.5)	54.1 (37.9)
baseline 60 min	83.0 (22.6)	52.0 (37.7)
baseline 90 min	66.3 (22.6)	44.7 (25.5)
baseline 120 min	61.7 (27.9)	39.0 (23.9)
baseline 180 min	39.9 (17.9)	30.0 (18.2)

Primary outcome: Change in AUC of Active GLP-1, Total GLP-1 and Total GIP Between Before and After Sitagliptin Treatment

Time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose. Mean (Standard Deviation). Unit: pmol*min/L

Measure	Non-responder n = 12	Responder n = 12
baseline AUC active GLP-1	2181.7 (1099.6)	1578.2 (807.5)
baseline AUC total GLP-1	5766.5 (4229.7)	3680.2 (3209.3)
baseline AUC total GIP	10216.7 (4226.1)	7575.6 (4608.3)
post-dose AUC active GLP-1	3898.5 (1547.5)	3535.1 (2769.1)
post-dose AUC total GLP-1	4794.5 (4949.8)	3373.6 (3169.8)
post-dose AUC total GIP	8784.6 (2449.2)	5929.4 (4711.2)
ΔAUC active GLP-1	1716.8 (1350.7)	1956.8 (2910.7)
ΔAUC total GLP-1	-972.0 (1030.4)	-306.7 (883.6)

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Non-responder	0 of 12 (0%)	0 of 12 (0%)	Not reported
Responder	0 of 12 (0%)	0 of 12 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Ji Hyun Kim, Dr principal investigator

The Catholic University of Korea

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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Sitagliptin in people with Type 2 Diabetes Mellitus, run by The Catholic University of Korea at 2 sites in South Korea.

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 13 inclusion and 6 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 14 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in South Korea. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 14 Dec 2015). 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?

Plasma Concentration of Active Glucagon-like Peptide 1 (GLP-1) Before and After Sitagliptin Treatment (time frame: 0, 15, 30, 45, 60, 90, 120, 180 min pre and post-dose). The study lists 4 primary outcomes in all. 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 NCT01449747.

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 14 Dec 2015.