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| ID | Type | Description | Link |
|---|---|---|---|
| MK-8655-002 | Other Identifier | Merck Protocol Number |
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This study will assess the initial safety, tolerability, pharmacokinetics, and pharmacodynamics of MK-8655, after single and multiple daily oral administrations to participants with Type 2 Diabetes (T2DM). The study will assess the reduction in fasting plasma glucose concentrations from baseline after multiple daily administrations of MK-8655.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-8655 80 mg/MK-8655 320 mg | Experimental | Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. |
|
| Placebo | Placebo Comparator | Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8655 | Drug | Participants will receive MK-8655 as a single dose on Day 1. Participants will receive MK-8655, once a day (q.d.), for 14 consecutive days (Day 3 through Day 16). MK-8655 doses may be adjusted downward based on the results of ongoing studies. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With One or More Adverse Events | An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to 14 days after the last dose of study drug (Up to 31 days) |
| Number of Participants Discontinuing Study Drug Due to an Adverse Event | An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | Up to 17 days |
| Fasting Plasma Glucose (FPG) | Blood for fasting plasma glucose (central laboratory) was obtained after at least 10 hours overnight fast. | Day 16 (Predose) |
| Measure | Description | Time Frame |
|---|---|---|
| True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24) | C24hr was log transformed and analyzed based on a linear mixed effects model containing fixed effects for treatment, day and treatment by day interaction and a random effect for the participant. | 24 hours post dose on Days 1, 7, and 14 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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Participant was a male or female (of non-child bearing potential) between 18 to 65 years of age with a diagnosis of Type 2 diabetes mellitus (T2DM) and was either drug naïve or was being treated with metformin only.
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-8655 80 mg/MK-8655 320 mg | Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. |
| FG001 | Placebo | Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All randomized participants
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-8655 80 mg/MK-8655 320 mg | Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Number of Participants With One or More Adverse Events | An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | All participants who received at least one dose of the investigational drug. | Posted | Count of Participants | Participants | Up to 14 days after the last dose of study drug (Up to 31 days) |
|
Up to 31 days
The analysis population was all participants who received at least one dose of the investigational drug.
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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 | MK-8655 80 mg/MK-8655 320 mg | Participants received a single dose of MK-8655, 80 mg on Day 1 and then MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Watering eyes | Eye 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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| Placebo | Drug | Participants will receive Placebo as a single dose on Day 1. Participants will receive Placebo, q.d., for 14 consecutive days (Day 3 through Day 16). |
|
| 24-Hour Weighted Mean Glucose (WMG) | The WMG provides an integrated assessment of the glycemic exposure over the 24-hour period. To reduce variability of the baseline (before any study drug administration) WMG, participants were domiciled in the test facility at least 36 hours prior to Day 1, where standard meals were provided, and physical activity was monitored. The WMG was derived from multiple glucose values collected during both fasting and post-meal periods. The sample scheme for the 18 point glucose measurements used in this study had many samples taken in the very early morning hours, as well as the first three hours after meals. WMG was calculated as the area under the curve (AUC) of the glucose concentrations divided by the duration of time of samples collected. | Day 15: Predose, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 18, 21, 23 hours post-dose. |
| Change From Baseline at 2 Hours Oral Glucose Tolerance Test | Plasma glucose excursion was assessed during an oral glucose tolerance test (oGTT) following a single dose administration of MK-8655 in participants with T2DM. | Baseline and 2 hours after dosing on Days 1, 3, and 16 |
Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | All randomized participants | Count of Participants | Participants |
|
| Placebo |
Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. |
|
|
| Primary | Number of Participants Discontinuing Study Drug Due to an Adverse Event | An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. | All participants who received at least one dose of the investigational drug. | Posted | Count of Participants | Participants | Up to 17 days |
|
|
|
| Primary | Fasting Plasma Glucose (FPG) | Blood for fasting plasma glucose (central laboratory) was obtained after at least 10 hours overnight fast. | The analysis population was participants who complied with the protocol sufficiently to ensure that these data would likely exhibit the effects of treatment, according to the underlying scientific model. Compliance covered such considerations as exposure to treatment, availability of measurements and absence of major protocol violations. | Posted | Mean | Standard Deviation | mg/dL | Day 16 (Predose) |
|
|
|
|
| Secondary | True Geometric Mean Plasma Concentrations of MK-8655 After Single and Multiple Drug Doses at 24 Hours Post Dose (C24) | C24hr was log transformed and analyzed based on a linear mixed effects model containing fixed effects for treatment, day and treatment by day interaction and a random effect for the participant. | The analysis population was participants who complied with the protocol sufficiently to ensure that these data would likely exhibit the effects of treatment, according to the underlying scientific model. No pharmacokinetic analysis for C24 was performed for participants receiving placebo. | Posted | Geometric Mean | Geometric Coefficient of Variation | uM | 24 hours post dose on Days 1, 7, and 14 |
|
|
|
| Secondary | 24-Hour Weighted Mean Glucose (WMG) | The WMG provides an integrated assessment of the glycemic exposure over the 24-hour period. To reduce variability of the baseline (before any study drug administration) WMG, participants were domiciled in the test facility at least 36 hours prior to Day 1, where standard meals were provided, and physical activity was monitored. The WMG was derived from multiple glucose values collected during both fasting and post-meal periods. The sample scheme for the 18 point glucose measurements used in this study had many samples taken in the very early morning hours, as well as the first three hours after meals. WMG was calculated as the area under the curve (AUC) of the glucose concentrations divided by the duration of time of samples collected. | The analysis population was participants who complied with the protocol sufficiently to ensure that these data would likely exhibit the effects of treatment, according to the underlying scientific model. Compliance covered such considerations as exposure to treatment, availability of measurements and absence of major protocol violations. | Posted | Mean | Standard Deviation | mg/dL | Day 15: Predose, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 18, 21, 23 hours post-dose. |
|
|
|
|
| Secondary | Change From Baseline at 2 Hours Oral Glucose Tolerance Test | Plasma glucose excursion was assessed during an oral glucose tolerance test (oGTT) following a single dose administration of MK-8655 in participants with T2DM. | The analysis population was participants who complied with the protocol sufficiently to ensure that these data would likely exhibit the effects of treatment, according to the underlying scientific model. Compliance covered such considerations as exposure to treatment, availability of measurements and absence of major protocol violations. | Posted | Mean | Standard Deviation | mg/dL | Baseline and 2 hours after dosing on Days 1, 3, and 16 |
|
|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 11 |
| 22 |
| EG001 | Placebo | Participants received a single dose of placebo to MK-8655, 80 mg on Day 1 and then placebo to MK-8655 320 mg, once daily, starting on Day 3 for 14 consecutive days. | 0 | 11 | 0 | 11 | 7 | 11 |
| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Catheter site pain | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Tiredness | General disorders | MedDRA 15.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Abrasion NOS | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| Ferritin decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
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| Glucose increased | Investigations | MedDRA 15.1 | Systematic Assessment |
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| Hypoglycaemic reaction | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
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| Low back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
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| Sore throat | 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. Sponsor review can be expedited to meet publication timelines.
| D004700 | Endocrine System Diseases |
|
| Day 14, MK-8655 320 mg, multiple doses |
|
| Day 3 |
|
|
| Day 16 |
|
|
Placebo-corrected (MK-8655 / placebo) |
| 0.065 |
| Geometric mean Ratio |
| 1.20 |
| 2-Sided |
| 95 |
| 0.98 |
| 1.47 |
| Other |
Day 3 |
| ANOVA | Placebo-corrected (MK-8655 / placebo) | 0.217 | Geometric Mean Ratio | 1.10 | 2-Sided | 95 | 0.89 | 1.37 | Other | Day 16 |