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| ID | Type | Description | Link |
|---|---|---|---|
| ONO-5435A | Other Identifier | ONO Pharmaceutical Company, Ltd. |
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This study will evaluate the effect of the addition of metformin once daily (q.d.) or twice daily (b.i.d.) to sitagliptin monotherapy in Japanese participants with Type 2 diabetes mellitus (T2DM) who have inadequate glycemic control with diet/exercise therapy and sitagliptin monotherapy. The primary hypotheses are that the addition of metformin 250 mg b.i.d. or metformin 500 mg q.d. is superior to the addition of placebo on the change from baseline in hemoglobin A1c (HbA1c) at 24 weeks and that the addition of metformin 500 mg q.d. is non-inferior to the addition of metformin 250 mg b.i.d. on the change from baseline in HbA1c at 24 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin 500 mg q.d. | Experimental | Participants will receive sitagliptin daily (continuing their pre-study dose), 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening. |
|
| Metformin 250 mg b.i.d. | Experimental | Participants will receive sitagliptin daily (continuing their pre-study dose), 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening. |
|
| Placebo | Placebo Comparator | Participants will receive sitagliptin daily (continuing their pre-study dose), 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sitagliptin | Drug | Sitagliptin, orally, 50 or 100 mg tablet (continuation of the pre-study dose) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) | Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups. | Baseline and Week 24 |
| Percentage of Participants Who Experienced at Least One Adverse Event | Up to 26 weeks | |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Based on a cLDA model with terms for treatment, other prior AHA therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups. |
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Inclusion Criteria:
Exclusion Criteria:
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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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| ID | Title | Description |
|---|---|---|
| FG000 | Metformin 500 mg q.d. | Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening. |
| FG001 | Metformin 250 mg b.i.d. | Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening. |
| FG002 | Placebo | Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants as treated population defined as all randomized participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Metformin 500 mg q.d. | Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening. |
| BG001 | Metformin 250 mg b.i.d. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) | Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups. | Per-protocol population defined as all randomized participants who had at least one measurement (baseline or post-randomization), with participants and/or selected data excluded due to protocol violations. | Posted | Least Squares Mean | 95% Confidence Interval | Percent of glycosylated hemoglobin | Baseline and Week 24 |
|
Up to 26 weeks
All participants as treated defined as all randomized participants who received at least one dose of study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metformin 500 mg q.d. | Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaphylactic reaction | Immune system disorders | MedDRA 15.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000068900 | Sitagliptin Phosphate |
| D008687 | Metformin |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Metformin | Drug | Metformin, orally, 500 mg daily (single dose; two 250 mg tablets) for 24 weeks |
|
| Metformin | Drug | Metformin, orally, 500 mg daily (divided dose; 250 mg tablet b.i.d.) for 24 weeks |
|
| Placebo | Drug | Placebo to match metformin 250 mg tablets, orally, for 24 weeks |
|
| Baseline and Week 24 |
| Participant moved or relocated |
|
| Withdrawal by Subject |
|
| Other |
|
Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening.
| BG002 | Placebo | Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Hemoglobin A1c (HbA1c) | Mean | Standard Deviation | Percent of glycosylated hemoglobin |
|
| Fasting plasma glucose (FPG) | Mean | Standard Deviation | mg/dL |
|
Participants received sitagliptin daily at pre-study dose, 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening.
| OG001 | Metformin 250 mg b.i.d. | Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening. |
| OG002 | Placebo | Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening. |
|
|
|
| Secondary | Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) | Based on a cLDA model with terms for treatment, other prior AHA therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups. | Per-protocol population defined as all randomized participants who had at least one measurement (baseline or post-randomization), with participants and/or selected data excluded due to protocol violations. | Posted | Least Squares Mean | 95% Confidence Interval | mg/dL | Baseline and Week 24 |
|
|
|
|
| Primary | Percentage of Participants Who Experienced at Least One Adverse Event | All participants as treated defined as all randomized participants who received at least one dose of study treatment. | Posted | Number | Percentage of participants | Up to 26 weeks |
|
|
|
| Primary | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | All participants as treated defined as all randomized participants who received at least one dose of study treatment. | Posted | Number | Participants | Up to 24 weeks |
|
|
|
| 4 |
| 138 |
| 29 |
| 138 |
| EG001 | Metformin 250 mg b.i.d. | Participants received sitagliptin daily at pre-study dose, 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening. | 2 | 133 | 35 | 133 |
| EG002 | Placebo | Participants received sitagliptin daily at pre-study dose, 2 matching placebo tablets in the morning and 1 matching placebo tablet in the evening. | 0 | 66 | 8 | 66 |
| Gastroenteritis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Sternal fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Brain stem infarction | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Any information identified by the sponsor as confidential must be deleted prior to submission.
| D004700 | Endocrine System Diseases |
| D011719 |
| Pyrazines |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
Based on a cLDA model with the terms listed above and a constraint that the mean baseline is the same for all treatment groups. |
| <0.001 |
| Difference in least squares means |
| -16.34 |
| 2-Sided |
| 95 |
| -23.62 |
| -9.06 |
| Superiority or Other |
| Difference in least squares mean | 2.25 | 2-Sided | 95 | -3.63 | 8.14 | Superiority or Other |