Type 2 Diabetes MellitusPhase 3NCT02577003

Double-blind Ipragliflozin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sitagliptin (MK-0431J-843)

A Phase 3 study testing Ipragliflozin and Sitagliptin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

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: Type 2 Diabetes Mellitus
What is being tested?: Ipragliflozin and Sitagliptin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 143 participants
Where: No sites listed yet
Study dates: 9 Nov 2015to 25 Nov 2016
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
Inadequate glycemic control on diet/exercise therapy and sitagliptin monotherapy
HbA1c ≥7.0% and ≤10.0% before study start

Who cannot join

History of Type 1 diabetes mellitus or a history of ketoacidosis
History of any of the following medications: thiazolidinediones (TZD) and/or insulin within 12 weeks prior to study participation and sodium glucose cotransporter 2 (SGLT2) inhibitors anytime
Currently has a urinary tract infection or genital infection with subjective symptom

About this study

Official title: A Phase III, Multicenter, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Trial to Assess the Safety and Efficacy of Addition of Ipragliflozin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sitagliptin Monotherapy in Addition to Diet and Exercise Therapy

This is a study to assess the safety and efficacy of the addition of ipragliflozin once daily in Japanese participants with Type 2 diabetes mellitus (T2DM) who have inadequate glycemic control on sitagliptin, diet, and exercise therapy. The primary hypothesis for this study is that the addition of ipragliflozin compared with placebo provides greater reduction in hemoglobin A1C (HbA1c) as assessed by change from baseline at Week 24.

Conditions: Type 2 Diabetes Mellitus
Being tested: Ipragliflozin, Placebo, Sitagliptin
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.

IpragliflozinDrug
50 mg tablet administered orally
PlaceboDrug
Placebo to ipragliflozin tablet administered orally
SitagliptinDrug
Also called Januvia®, Tesavel®, Xelevia®, Ristaben®, Glactiv®
Background medication; 50 mg tablet administered orally

Study groups in NCT02577003
Study group	Role	What they receive
Ipragliflozin + Sitagliptin	Experimental	Ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise. Receives: Drug: Ipragliflozin; Drug: Sitagliptin
Placebo + Sitagliptin	Active comparator	Placebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise. Receives: Drug: Placebo; Drug: Sitagliptin

What is being measured

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

Change From Baseline in HbA1c at Week 24
HbA1c is measured as percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. Statistical analysis based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline HbA1c is the same for both treatment groups.
Measured: Baseline and Week 24
Percentage of Participants Who Experienced at Least One Adverse Event (AE)
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 26 weeks
Percentage of Participants Who Discontinued Study Drug Due to an AE
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 24 weeks

Secondary outcomes (4)

Change From Baseline in FPG at Week 24
Change from baseline in FPG at Week 24 is defined as Week 24 FPG minus Week 0 FPG. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline FPG is the same for both treatment groups.
Measured: Baseline and Week 24
Change From Baseline in 2-hr PMG at Week 24
Change from baseline in 2-hr PMG at Week 24 is defined as Week 24 2-hr PMG minus Week 0 2-hr PMG. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline 2-hr PMG is the same for both treatment groups.
Measured: Baseline and Week 24
Change From Baseline in Glucose Total AUC0-2hr After Meal at Week 24
Change from baseline in glucose total AUC0-2hr after meal at Week 24 is defined as Week 24 glucose total AUC0-2hr after a meal minus Week 0 glucose total AUC0-2hr after a meal. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs and treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline glucose total AUC0-2hr after meal is the same for both treatment groups.
Measured: Baseline and Week 24 (just before the loading meal [0 min], 30 min, 60 min and 120 min)
Change From Baseline in Body Weight at Week 24
Change from baseline in body weight at Week 24 is defined as Week 24 body weight minus Week 0 body weight. Statistical analysis based on a cLDA model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs and treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline body weight is the same for both treatment groups.
Measured: Baseline and Week 24

Timeline

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

9 Nov 201525 Nov 2016

First posted15 Oct 2015 (estimated)
Study start9 Nov 2015
Primary completion25 Nov 2016
Study completion25 Nov 2016

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 (1)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe 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: 143 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02577003
Sponsor's protocol ID: 0431J-843
Other IDs: 153097
Status last verified: Aug 2018
First submitted: 14 Oct 2015
Last updated: 4 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Kaku K, Kadowaki T, Seino Y, Okamoto T, Shirakawa M, Sato A, O'Neill EA, Engel SS, Kaufman KD. Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes and inadequate glycaemic control on sitagliptin. Diabetes Obes Metab. 2021 Sep;23(9):2099-2108. doi: 10.1111/dom.14448. Epub 2021 Jun 15.
PubMed 34033212

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?

Official record

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III, Multicenter, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Trial to Assess the Safety and Efficacy of Addition of Ipragliflozin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Sitagliptin Monotherapy in Addition to Diet and Exercise Therapy
ClinicalTrials.gov ID: NCT02577003
Acronym / sponsor ID: 0431J-843
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 143 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 9 Nov 2015
Primary completion: 25 Nov 2016 (actual)
Study completion: 25 Nov 2016 (actual)
First posted: 15 Oct 2015 (estimated)
Results: Posted 7 Mar 2018

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
Ipragliflozin + Sitagliptin	Experimental	Drug: Ipragliflozin, Drug: SitagliptinIpragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.
Placebo + Sitagliptin	Active comparator	Drug: Placebo, Drug: SitagliptinPlacebo to ipragliflozin once daily for 24 weeks in addition to sitagliptin, diet, and exercise.

Who may qualify

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

Key inclusion criteria (3 listed)

Type 2 diabetes mellitus
Inadequate glycemic control on diet/exercise therapy and sitagliptin monotherapy
HbA1c ≥7.0% and ≤10.0% before study start

Key exclusion criteria (3 listed)

History of Type 1 diabetes mellitus or a history of ketoacidosis
History of any of the following medications: thiazolidinediones (TZD) and/or insulin within 12 weeks prior to study participation and sodium glucose cotransporter 2 (SGLT2) inhibitors anytime
Currently has a urinary tract infection or genital infection with subjective symptom

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
Ipragliflozin50 mg tablet administered orally	Drug	Ipragliflozin + Sitagliptin
PlaceboPlacebo to ipragliflozin tablet administered orally	Drug	Placebo + Sitagliptin
SitagliptinAlso: Januvia®, Tesavel®, Xelevia®, Ristaben®, Glactiv®Background medication; 50 mg tablet administered orally	Drug	Ipragliflozin + Sitagliptin, Placebo + Sitagliptin

Primary outcome

Change From Baseline in HbA1c at Week 24
Time frame: Baseline and Week 24
HbA1c is measured as percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. Statistical analysis based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, treatment by time by prior use of AHAs, and baseline eGFR value with the constraint that the mean baseline HbA1c is the same for both treatment groups.
Percentage of Participants Who Experienced at Least One Adverse Event (AE)
Time frame: Up to 26 weeks
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Who Discontinued Study Drug Due to an AE
Time frame: Up to 24 weeks
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

4 secondary outcomes

Change From Baseline in FPG at Week 24
Time frame: Baseline and Week 24
Change From Baseline in 2-hr PMG at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Glucose Total AUC0-2hr After Meal at Week 24
Time frame: Baseline and Week 24 (just before the loading meal [0 min], 30 min, 60 min and 120 min)
Change From Baseline in Body Weight at Week 24
Time frame: Baseline and Week 24

Results and safety

Results posted to the registry on 7 Mar 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ipragliflozin + Sitagliptin	73	71
Placebo + Sitagliptin	70	65

Primary outcome: Change From Baseline in HbA1c at Week 24

Time frame: Baseline and Week 24. Least squares mean (95% Confidence Interval). Unit: Percent

Measure	Ipragliflozin + Sitagliptin n = 73	Placebo + Sitagliptin n = 70
Value	-0.84 (-0.99 to -0.69)	-0.07 (-0.22 to 0.09)

Ipragliflozin + Sitagliptin vs Placebo + Sitagliptin: Difference in least squares means: -0.77 (95% CI -0.98 to -0.57), p <0.001, Constrained longitudinal data analysis

Population analysed: All randomized participants who received at least one dose of treatment period study medication and have at least one measurement of HbA1c (baseline or post-baseline).

Primary outcome: Percentage of Participants Who Experienced at Least One Adverse Event (AE)

Time frame: Up to 26 weeks. Number. Unit: Percentage of participants

Measure	Ipragliflozin + Sitagliptin n = 73	Placebo + Sitagliptin n = 70
Value	50.7	65.7

Population analysed: All randomized participants who received at least one dose of study medication.

Primary outcome: Percentage of Participants Who Discontinued Study Drug Due to an AE

Time frame: Up to 24 weeks. Number. Unit: Percentage of participants

Measure	Ipragliflozin + Sitagliptin n = 73	Placebo + Sitagliptin n = 70
Value	2.7	5.7

Population analysed: All randomized participants who received at least one dose of study medication.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 26 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ipragliflozin + Sitagliptin	2 of 73 (2.7%)	12 of 73 (16.4%)	Not reported
Placebo + Sitagliptin	4 of 70 (5.7%)	15 of 70 (21.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34033212Kaku K, Kadowaki T, Seino Y, Okamoto T, Shirakawa M, Sato A, O'Neill EA, Engel SS, Kaufman KD. Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes and inadequate glycaemic control on sitagliptin. Diabetes Obes Metab. 2021 Sep;23(9):2099-2108. doi: 10.1111/dom.14448. Epub 2021 Jun 15.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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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.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ipragliflozin and Sitagliptin in people with Type 2 Diabetes Mellitus, run by Merck Sharp & Dohme LLC.

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 3 inclusion and 3 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 4 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

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 7 Mar 2018). 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 From Baseline in HbA1c at Week 24 (time frame: Baseline and Week 24). The study lists 3 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 NCT02577003, which also lists 1 linked publication.

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 4 Sep 2018.