Type 2 Diabetes MellitusPhase 3NCT02577016

Double-blind Sitagliptin Add-on Study in Japanese Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Ipragliflozin (MK-0431J-842)

A Phase 3 study testing Sitagliptin and Ipragliflozin 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?: Sitagliptin and Ipragliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 141 participants
Where: No sites listed yet
Study dates: 5 Nov 2015to 18 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 ipragliflozin 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, sitagliptin within 8 weeks prior to study participation.
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 Sitagliptin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Ipragliflozin Monotherapy in Addition to Diet and Exercise Therapy

This is a study to assess the safety and efficacy of the addition of sitagliptin in Japanese participants with Type 2 diabetes mellitus (T2DM) who have inadequate glycemic control on ipragliflozin, diet, and exercise therapy. The primary hypothesis of the study is that the addition of sitagliptin once daily compared with placebo provides greater reduction in hemoglobin A1C (HbA1c) as assessed by change from baseline (Week 0) to Week 24.

Conditions: Type 2 Diabetes Mellitus
Being tested: Sitagliptin, Placebo, Ipragliflozin
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®, Tesavel®, Xelevia®, Ristaben®, Glactiv®
50 mg tablet administered orally
PlaceboDrug
Placebo to sitagliptin administered orally
IpragliflozinDrug
50 mg tablet administered orally as background medication

Study groups in NCT02577016
Study group	Role	What they receive
Sitagliptin + Ipragliflozin	Experimental	Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise. Receives: Drug: Sitagliptin; Drug: Ipragliflozin
Placebo + Ipragliflozin	Active comparator	Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise. Receives: Drug: Placebo; Drug: Ipragliflozin

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, and treatment by time by prior use of AHAs with the constraint that the mean baseline 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 (3)

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, and treatment by time by prior use of AHAs 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 Area Under the Plasma Concentration Curve From Hour 0 to Hour 2 (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 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 loading meal [0 min], 30 min, 60 min and 120 min)
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, and treatment by time by prior use of AHAs with the constraint that the mean baseline FPG 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.

5 Nov 201518 Nov 2016

First posted15 Oct 2015 (estimated)
Study start5 Nov 2015
Primary completion18 Nov 2016
Study completion18 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: 141 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02577016
Sponsor's protocol ID: 0431J-842
Other IDs: 153096
Status last verified: Aug 2018
First submitted: 14 Oct 2015
Last updated: 31 Aug 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

Seino Y, Kaku K, Kadowaki T, Okamoto T, Sato A, Shirakawa M, O'Neill EA, Engel SS, Kaufman KD. A randomized, placebo-controlled trial to assess the efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes and inadequate glycaemic control on ipragliflozin. Diabetes Obes Metab. 2021 Jun;23(6):1342-1350. doi: 10.1111/dom.14346. Epub 2021 Feb 28.
PubMed 33565686

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 31 Aug 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 Sitagliptin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Ipragliflozin Monotherapy in Addition to Diet and Exercise Therapy
ClinicalTrials.gov ID: NCT02577016
Acronym / sponsor ID: 0431J-842
Conditions: Type 2 Diabetes Mellitus
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 141 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 5 Nov 2015 (actual)
Primary completion: 18 Nov 2016 (actual)
Study completion: 18 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
Sitagliptin + Ipragliflozin	Experimental	Drug: Sitagliptin, Drug: IpragliflozinSitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise.
Placebo + Ipragliflozin	Active comparator	Drug: Placebo, Drug: IpragliflozinPlacebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to 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 ipragliflozin 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, sitagliptin within 8 weeks prior to study participation.
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
SitagliptinAlso: Januvia®, Tesavel®, Xelevia®, Ristaben®, Glactiv®50 mg tablet administered orally	Drug	Sitagliptin + Ipragliflozin
PlaceboPlacebo to sitagliptin administered orally	Drug	Placebo + Ipragliflozin
Ipragliflozin50 mg tablet administered orally as background medication	Drug	Placebo + Ipragliflozin, Sitagliptin + Ipragliflozin

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, and treatment by time by prior use of AHAs with the constraint that the mean baseline 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.

3 secondary outcomes

Change From Baseline in 2-hr PMG at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Glucose Total Area Under the Plasma Concentration Curve From Hour 0 to Hour 2 (AUC0-2hr) After Meal at Week 24
Time frame: Baseline and Week 24 (just before loading meal [0 min], 30 min, 60 min and 120 min)
Change From Baseline in FPG 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
Sitagliptin + Ipragliflozin	70	68
Placebo + Ipragliflozin	71	69

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	Sitagliptin + Ipragliflozin n = 70	Placebo + Ipragliflozin n = 71
Value	-0.69 (-0.85 to -0.53)	0.14 (-0.02 to 0.29)

Sitagliptin + Ipragliflozin vs Placebo + Ipragliflozin: Difference in least squares means: -0.83 (95% CI -1.05 to -0.62), 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	Sitagliptin + Ipragliflozin n = 70	Placebo + Ipragliflozin n = 71
Value	54.3	63.4

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	Sitagliptin + Ipragliflozin n = 70	Placebo + Ipragliflozin n = 71
Value	2.9	0.0

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

3 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
Sitagliptin + Ipragliflozin	3 of 70 (4.3%)	10 of 70 (14.3%)	Not reported
Placebo + Ipragliflozin	0 of 71 (0%)	18 of 71 (25.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33565686Seino Y, Kaku K, Kadowaki T, Okamoto T, Sato A, Shirakawa M, O'Neill EA, Engel SS, Kaufman KD. A randomized, placebo-controlled trial to assess the efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes and inadequate glycaemic control on ipragliflozin. Diabetes Obes Metab. 2021 Jun;23(6):1342-1350. doi: 10.1111/dom.14346. Epub 2021 Feb 28.
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 Sitagliptin and Ipragliflozin 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 31 Aug 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 NCT02577016, 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 31 Aug 2018.