Not provided
Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2009_564 | Other Identifier | Merck Registration Number | |
| CTRI/2009/091/000614 | Registry Identifier | CTRI |
Not provided
Not provided
Not provided
Upon interim analysis, sufficient data was accrued to assess study hypotheses.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study assessed the safety and efficacy of MK-3577. The primary efficacy hypothesis was that, after 4 weeks of treatment, either the morning (AM) administration or the evening (PM) administration of MK-3577 provides superior reduction of 24-hour weighted mean glucose (WMG) levels compared to placebo (PLA). The primary safety hypothesis was that MK-3577 is well tolerated compared to placebo.
This was a 4-period/5-treatment crossover study. Each period was 4 weeks. The 5 treatments consisted of MK-3577 10 mg once daily (QD) in the AM, MK-3577 6 mg QD in the evening (PM), MK-3577 25 mg twice daily (BID), metformin 1000 mg BID, and placebo to MK-3577/placebo to metformin. Participants were to be randomized to one of 14 treatment sequence arms. A subset of participants in each group was to domicile (stay overnight) at selected clinical sites at Baseline, Week 4 (end of Period 1), and Week 8 (end of Period 2) to undergo 24-hr blood sample.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1) | Experimental | Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2. |
|
| MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2) | Experimental | Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2. |
|
| MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3) | Experimental | Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed MK- 3577 25 mg BID for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. |
|
| MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-3577 | Drug | MK-3577 oral tablets totaling 6 mg in the evening (PM), 10 mg in the morning (AM), or 25 mg twice daily (BID) depending upon randomization, administered during a 4 week treatment period. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (BL) After 4-Week Treatment in Weighted Mean Glucose (WMG) | The primary efficacy outcome in this study was the assessment of 24-hour weighted mean glucose (WMG) levels for domiciled participants after 4-week treatment (Periods 1 and 2 only). At selected study sites, a subset of participants domiciled (stayed) overnight and underwent 24-hour blood sampling at the Week 0 Visit (Baseline), Week 4 Visit (end of Period 1), and Week 8 Visit (end of Period 2). Domiciled participants were not expected to follow a weight-maintaining diet while receiving standard meals from a dietician or licensed healthcare professional. WMG was calculated as the weighted average value of the glucose from the 24-hour blood sample (for Baseline, Week 4, and Week 8) and analyzed using a Longitudinal Data Analysis (LDA) model. Results were expressed as the change from baseline after 4-week treatment in 24-hour WMG. | Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit |
| Number of Participants With At Least One Adverse Event (AE) in the Treatment or Post-Treatment Periods | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE. | From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks). |
| Number of Participants Who Discontinued Study Treatment Due to an AE | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE. | From first dose of study treatment (Week 0 Visit) to Week 16 Visit (up to 16 weeks). |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline (BL) After 4-Week Treatment in Fasting Plasma Glucose (FPG) | Fasting blood samples were obtained during study site visits at Baseline (Week 0 Visit) and Week 4 of each treatment period (Week 4 Visit, Week 8 Visit, Week 12 Visit, Week 16 Visit). Participants were counseled to fast (no food or drink except water and non-study medications, as directed) for at least 12 hours prior to all study visits. FPG was analyzed using an LDA model, and change from baseline (Week 0) after 4-week treatment in FPG was reported. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
Not provided
Not provided
Not provided
| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis Link | View IPD |
Not provided
Not provided
Not provided
A total of 118 participants were randomized to one of 14 treatment sequence arms on this cross-over study. Each participant received 4 out of 5 treatments over 4 treatment periods. Before randomization, participants who had prior antihyperglycemic agent (AHA) treatment had a 4-week AHA wash-off, and all participants had a 2-week placebo run-in.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | PLA→MK-3577 QD AM→MK-3577 QD PM→MK-3577 BID (Arm 1) | Participants received oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants also received placebo to metformin during Period 1 and Period 2. |
| FG001 | MK-3577 QD AM→PLA→MK-3577 BID→MK-3577 QD PM (Arm 2) | Participants received oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Domiciled participants also received placebo to metformin during Period 1 and Period 2. |
| FG002 | MK-3577 QD PM→MK-3577 BID→PLA→MK-3577 QD AM (Arm 3) | Participants received oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed MK- 3577 25 mg BID for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. |
| FG003 | MK-3577 BID→MK-3577 QD PM→MK-3577 QD AM→PLA (Arm 4) | Participants received oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4. |
| FG004 | PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5) | Participants received oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. |
| FG005 | MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6) | Participants received oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. |
| FG006 | MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7) | Participants received oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4. |
| FG007 | MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8) | Participants received oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. |
| FG008 | PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9) | Participants received oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during period 4. Domiciled participants also received placebo to metformin during Period 1 and Period 2. |
| FG009 | MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10) | Participants received oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4. |
| FG010 | MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11) | Participants received oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants also received placebo to metformin during Period 1 and Period 2. |
| FG011 | MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12) | Participants received oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. |
| FG012 | PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13) | Domiciled participants received oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2. |
| FG013 | METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14) | Domiciled participants received oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
|
| ||||||||||||||||||
| Period 2 |
| |||||||||||||||||||
| Period 3 |
| |||||||||||||||||||
| Period 4 |
| |||||||||||||||||||
| Post-study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Randomized Participants | All randomized participants who took at least one dose of study treatment |
| 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 (BL) After 4-Week Treatment in Weighted Mean Glucose (WMG) | The primary efficacy outcome in this study was the assessment of 24-hour weighted mean glucose (WMG) levels for domiciled participants after 4-week treatment (Periods 1 and 2 only). At selected study sites, a subset of participants domiciled (stayed) overnight and underwent 24-hour blood sampling at the Week 0 Visit (Baseline), Week 4 Visit (end of Period 1), and Week 8 Visit (end of Period 2). Domiciled participants were not expected to follow a weight-maintaining diet while receiving standard meals from a dietician or licensed healthcare professional. WMG was calculated as the weighted average value of the glucose from the 24-hour blood sample (for Baseline, Week 4, and Week 8) and analyzed using a Longitudinal Data Analysis (LDA) model. Results were expressed as the change from baseline after 4-week treatment in 24-hour WMG. | All randomized domiciled participants receiving ≥1 dose of therapy and having 24-hour WMG measurement either at BL or end of Treatment Period 1 or 2. Number of Participants Analyzed=number of participants included in LDA model. Participants in MK-3577 25 mg BID group did not undergo 24-hour glucose sampling and were not analyzed. | Posted | Least Squares Mean | Standard Error | mg/dL | Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit |
From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks).
All randomized participants who took ≥1 dose of study treatment (N=118). Because this was a cross-over study, participants were counted in more than one treatment group. AEs were reported by the treatment that participants were receiving at the time of the event. Not all participants received all treatments.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received a placebo tablet matching the respective MK-3577 dose (10 mg, 6 mg, 25 mg) and metformin, depending upon randomization, for 4 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Coronary artery disease | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
A pre-specified interim analysis of the efficacy and safety data for the initial cohort of participants in this study (Cohort 1) determined that sufficient data had been accrued to assess the study hypotheses, thus the study was discontinued.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vice President, Late Stage Development Group Leader | 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 |
Not provided
Not provided
| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4. |
|
| PLA→MK-3577 BID→MK-3577 QD AM→MK-3577 QD PM (Arm 5) | Experimental | Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. |
|
| MK-3577 QD AM→MK-3577 QD PM→PLA→MK-3577 BID (Arm 6) | Experimental | Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. |
|
| MK-3577 QD PM→MK-3577 QD AM→MK-3577 BID→PLA (Arm 7) | Experimental | Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4. |
|
| MK-3577 BID→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 8) | Experimental | Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. |
|
| PLA→MK-3577 QD PM→MK-3577 BID→MK-3577 QD AM (Arm 9) | Experimental | Participants were to receive oral treatment with dose-matched placebo to MK-3577 for 4 weeks during Period 1, followed by MK-3577 6 mg QD PM for 4 weeks during Period 2, followed by MK-3577 25 mg BID for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2. |
|
| MK-3577 QD AM→MK-3577 BID→MK-3577 QD PM→PLA (Arm 10) | Experimental | Participants were to receive oral treatment with MK-3577 10 mg QD AM for 4 weeks during Period 1, followed by MK-3577 25 mg BID for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 4. |
|
| MK-3577 QD PM→PLA→MK-3577 QD AM→MK-3577 BID (Arm 11) | Experimental | Participants were to receive oral treatment with MK-3577 6 mg QD PM for 4 weeks during Period 1, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 25 mg BID for 4 weeks during Period 4. Domiciled participants were also to receive placebo to metformin during Period 1 and Period 2. |
|
| MK-3577 BID→MK-3577 QD AM→PLA→MK-3577 QD PM (Arm 12) | Experimental | Participants were to receive oral treatment with MK-3577 25 mg BID for 4 weeks during Period 1, followed by MK-3577 10 mg QD AM for 4 weeks during Period 2, followed by dose-matched placebo to MK-3577 for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. |
|
| PLA→METF→MK-3577 QD AM→MK-3577 QD PM (Arm 13) | Experimental | Domiciled participants were to receive oral treatment with dose-matched placebo to metformin (METF) for 4 weeks during Period 1, followed by metformin 1000 mg BID for 4 weeks during Period 2, followed by MK-3577 10 mg QD AM for 4 weeks during Period 3, followed by MK-3577 6 mg QD PM for 4 weeks during Period 4. Participants in this arm were administered metformin placebo during Period 1 and active metformin during Period 2. |
|
| METF→PLA→MK-3577 QD PM→MK-3577 QD AM (Arm 14) | Experimental | Domiciled participants were to receive oral treatment with metformin 1000 mg BID for 4 weeks during Period 1, followed by dose-matched placebo to metformin for 4 weeks during Period 2, followed by MK-3577 6 mg QD PM for 4 weeks during Period 3, followed by MK-3577 10 mg QD AM for 4 weeks during Period 4. Participants in this arm were administered active metformin during Period 1 and metformin placebo during Period 2. |
|
| Placebo to MK-3577 | Drug | Dose-matched placebo tablets to MK-3577 administered during a 4 week treatment period |
|
| Metformin | Drug | Two 500 mg tablets of metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period. |
|
| Placebo to Metformin | Drug | Two placebo tablets to metformin were administered twice daily (2000 mg total daily dose) to domiciled participants during a 4 week treatment period. |
|
| Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, Week 16 Visit |
| Change From BL After 4-Week Treatment in 2-hour Post-Meal Glucose (PMG) Levels | Two-hour PMG was analyzed in both non-domiciled and domiciled participants. Non-domiciled participants completed a 3-point meal tolerance test (MTT) at Week 0 (Baseline) and Week 4 Visits of Treatment Period 1. Participants completed 12-hr fasting prior to the Week 0 (Baseline) and Week-4 clinic visits. Fasting blood samples were obtained at the beginning of these clinic visits, after which participants consumed a standardized meal (1 nutrition bar and 1 can of nutrition drink), and then completed the MTT, in which plasma glucose was measured at 30 min and 120 min (2 hr) post-meal. The 2-hr PMG data also include data from domiciled participants, based on 2-hr post-morning meal glucose levels in the 24-hr blood glucose sample at the Week 4 and Week 8 Visits. The 2-hour PMG was analyzed using an LDA model, and change from baseline (Week 0) after 4-week treatment in 2-hour PMG was reported. | Week 0 Visit (Baseline), Week 4 Visit, Week 8 visit |
| Percentage Change From Baseline (BL) After 4-Week Treatment in Low-Density Lipoprotein C (LDL-C) Levels | Blood samples were obtained from all participants to measure LDL-C levels at Week 0 (Baseline) and Week 4 of each treatment period (Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit). For each visit, LDL-C was measured over 2 days. The average of duplicate measurements (when available) was used in the analysis. | Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit |
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Abnormal Triglycerides |
|
| Lost to Follow-up |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
|
|
| Secondary | Change From Baseline (BL) After 4-Week Treatment in Fasting Plasma Glucose (FPG) | Fasting blood samples were obtained during study site visits at Baseline (Week 0 Visit) and Week 4 of each treatment period (Week 4 Visit, Week 8 Visit, Week 12 Visit, Week 16 Visit). Participants were counseled to fast (no food or drink except water and non-study medications, as directed) for at least 12 hours prior to all study visits. FPG was analyzed using an LDA model, and change from baseline (Week 0) after 4-week treatment in FPG was reported. | All randomized participants receiving ≥1 dose of therapy and having FPG measurement either at BL or end of Treatment Period. Number of Participants Analyzed=number of participants included in the LDA model. | Posted | Least Squares Mean | Standard Error | mg/dL | Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, Week 16 Visit |
|
|
|
|
| Secondary | Change From BL After 4-Week Treatment in 2-hour Post-Meal Glucose (PMG) Levels | Two-hour PMG was analyzed in both non-domiciled and domiciled participants. Non-domiciled participants completed a 3-point meal tolerance test (MTT) at Week 0 (Baseline) and Week 4 Visits of Treatment Period 1. Participants completed 12-hr fasting prior to the Week 0 (Baseline) and Week-4 clinic visits. Fasting blood samples were obtained at the beginning of these clinic visits, after which participants consumed a standardized meal (1 nutrition bar and 1 can of nutrition drink), and then completed the MTT, in which plasma glucose was measured at 30 min and 120 min (2 hr) post-meal. The 2-hr PMG data also include data from domiciled participants, based on 2-hr post-morning meal glucose levels in the 24-hr blood glucose sample at the Week 4 and Week 8 Visits. The 2-hour PMG was analyzed using an LDA model, and change from baseline (Week 0) after 4-week treatment in 2-hour PMG was reported. | All randomized participants receiving ≥1 dose of therapy and having MTT measurement either at Week 0 (BL) or end of Treatment Period 1. N=number of participants included in the Longitudinal Data Analysis (LDA) model | Posted | Least Squares Mean | Standard Error | mg/dL | Week 0 Visit (Baseline), Week 4 Visit, Week 8 visit |
|
|
|
|
| Secondary | Percentage Change From Baseline (BL) After 4-Week Treatment in Low-Density Lipoprotein C (LDL-C) Levels | Blood samples were obtained from all participants to measure LDL-C levels at Week 0 (Baseline) and Week 4 of each treatment period (Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit). For each visit, LDL-C was measured over 2 days. The average of duplicate measurements (when available) was used in the analysis. | All randomized participants who took at least 1 dose of study treatment and had a valid reading at timepoint. | Posted | Least Squares Mean | 90% Confidence Interval | percentage change from BL | Week 0 Visit (Baseline), Week 4 Visit, Week 8 Visit, Week 12 Visit, and Week 16 Visit |
|
|
|
|
| Primary | Number of Participants With At Least One Adverse Event (AE) in the Treatment or Post-Treatment Periods | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE. | All randomized participants who took ≥1 dose of study treatment (N=118). Because this was a cross-over study, participants were counted in more than one treatment group. AEs were reported by the treatment that participants were receiving at the time of the event. Not all participants received all treatments. | Posted | Number | Participants | From first dose of study treatment (Week 0 Visit) to Week 18 Post-study Visit (up to 18 weeks). |
|
|
|
| Primary | Number of Participants Who Discontinued Study Treatment Due to an AE | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE. | All randomized participants who took ≥1 dose of study treatment (N=118). Because this was a cross-over study, participants were counted in more than one treatment group. AEs were reported by the treatment that participants were receiving at the time of the event. Not all participants received all treatments. | Posted | Number | Participants | From first dose of study treatment (Week 0 Visit) to Week 16 Visit (up to 16 weeks). |
|
|
|
| 1 |
| 108 |
| 3 |
| 108 |
| EG001 | MK-3577 AM | Participants received 10 mg MK-3577 orally QD in the AM for 4 weeks. | 2 | 106 | 4 | 106 |
| EG002 | MK-3577 PM | Participants received 6 mg MK-3577 orally QD in the PM for 4 weeks. | 2 | 105 | 3 | 105 |
| EG003 | MK-3577 BID | Participants received 25 mg MK-3577 orally BID for 4 weeks. | 0 | 89 | 5 | 89 |
| EG004 | METF BID | Domiciled participants received metformin 1000 mg orally BID for 4 weeks (received during Period 1 or 2 only). | 0 | 18 | 6 | 18 |
| Myocardial infarction | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Necrotising fasciitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA 13.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
The SPONSOR has 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. SPONSOR review can be expedited to meet publication guidelines.
| D004700 | Endocrine System Diseases |
| Analysis based on an LDA model including terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). The LDA-model test was conducted at alpha level=0.10 (two sided). | LDA Model | Between-group difference (MK-3577-placebo) of LSM changes from BL to a given time point and 90% confidence intervals were estimated from LDA model. | <0.001 | LSM Difference | -21.8 | 2-Sided | 90 | -27.8 | -15.8 | Superiority or Other |
| Analysis based on an LDA model including terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). The LDA-model test was conducted at alpha level=0.10 (two sided). | LDA Model | Between-group difference (MK-3577-placebo) of LSM changes from BL to a given time point and 90% confidence intervals were estimated from LDA model. | <0.001 | LSM Difference | -36.0 | 2-Sided | 90 | -42.0 | -30.0 | Superiority or Other |
| Analysis based on an LDA model including terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). The LDA-model test was conducted at alpha level=0.10 (two sided). | LDA Model | Between-group difference (metformin-placebo) of LSM changes from BL to a given time point and 90% confidence intervals were estimated from LDA model. | 0.001 | LSM Difference | -20.0 | 2-Sided | 90 | -30.0 | -10.1 | Superiority or Other |
| Analysis based on an LDA model including terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). The LDA-model test was conducted at alpha level=0.10 (two sided). | LDA Model | Between-group difference (MK-3577-placebo) of LSM changes from BL to a given time point and 90% confidence intervals were estimated from LDA model. | 0.063 | LSM Difference | -20.4 | 2-Sided | 90 | -38.4 | -2.4 | Superiority or Other |
| Analysis based on an LDA model including terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). The LDA-model test was conducted at alpha level=0.10 (two sided). | LDA Model | Between-group difference (MK-3577-placebo) of LSM changes from BL to a given time point and 90% confidence intervals were estimated from LDA model. | <0.001 | LSM Difference | -78.1 | 2-Sided | 90 | -96.4 | -59.8 | Superiority or Other |
| Analysis based on an LDA model including terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). The LDA-model test was conducted at alpha level=0.10 (two sided). | LDA Model | Between-group difference (metformin-placebo) of LSM changes from BL to a given time point and 90% confidence intervals were estimated from LDA model. | <0.001 | LSM Difference | -49.4 | 2-Sided | 90 | -66.9 | -31.8 | Superiority or Other |
| LDL-C values after log transformation were analyzed using a constrained LDA model that included terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). Percentage change from baseline in LDL-C after 4-week treatment was reported, after back-transformation using the delta method with an alpha-level of 0.10 (2-sided). | LDA Model | 0.060 | LSM Difference | 4.5 | 2-Sided | 90 | 0.6 | 8.4 | Superiority or Other |
| LDL-C values after log transformation were analyzed using a constrained LDA model that included terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). Percentage change from baseline in LDL-C after 4-week treatment was reported, after back-transformation using the delta method with an alpha-level of 0.10 (2-sided). | LDA Model | 0.002 | LSM Difference | 7.8 | 2-Sided | 90 | 3.8 | 11.7 | Superiority or Other |
| LDL-C values after log transformation were analyzed using a constrained LDA model that included terms for treatment, period, the interaction of treatment by period, prior antihyperglycemic therapy status (yes/no), and randomization stratum (participation in domiciled visits [yes/no]). Percentage change from baseline in LDL-C after 4-week treatment was reported, after back-transformation using the delta method with an alpha-level of 0.10 (2-sided). | LDA Model | 0.248 | LSM Difference | -3.9 | 2-Sided | 90 | -10.2 | 2.3 | Superiority or Other |