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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-021832-32 | EudraCT Number |
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This was designed as a two part study comprising sequential double-dummy, placebo controlled 3-period randomized crossover studies. The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of different doses and dose regimens of MK-8266. Only Part I of the study was completed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part I - Sequence ABC | Experimental | Treatment A in Period 1, Treatment B in Period 2, and Treatment C in Period 3 |
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| Part I - Sequence ACB | Experimental | Treatment A in Period 1, Treatment C in Period 2, and Treatment B in Period 3 |
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| Part I - Sequence BCA | Experimental | Treatment B in Period 1, Treatment C in Period 2, and Treatment A in Period 3 |
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| Part I - Sequence BAC | Experimental | Treatment B in Period 1, Treatment A in Period 2, and Treatment C in Period 3 |
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| Part I - Sequence CAB | Experimental | Treatment C in Period 1, Treatment A in Period 2, and Treatment B in Period 3 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment A | Drug | MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events (AEs) | The number of participants with one or more clinical or laboratory AEs was assessed. 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. | MK-8266 1.3 mg BID and 0.9 mg FDD groups: Up to Day 4 in each period; MK-8266 1 mg QD group: the last AE was reported on day 10 after the last dose; Placebo group: Up to 10-14 days after the last dose of placebo |
| Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Days 1 and 3 | The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided. | Pre-dose and 0.5, 1, 2, 4, and 8 hours after dosing on Day 1, and pre-dose and 4 and 8 hours after dosing on Day 3 of each period |
| Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Day 4 | The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided. | Predose and 2, 4, and 8 hours after dosing on Day 4 of each period |
| Maximum Plasma Concentration (Cmax) of MK-8266 on Day 1 and Day 3 | The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided. | Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3 |
| Maximum Plasma Concentration (Cmax) of MK-8266 on Day 4 | The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided. |
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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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The same participants in Part 1 were to continue in Part 2, pending the planned evaluation of Part 1 pharmacodynamic results. Based on the Part 1 results, no participants continued to Part 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence ABC | MK-8266 1.3 mg BID, then MK-8266 0.9 mg FDD, then Placebo |
| FG001 | Sequence ACB | MK-8266 1.3 mg BID, then Placebo, then MK-8266 0.9 mg FDD |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Part 1: Period 1 |
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| Part I - Sequence CBA | Experimental | Treatment C in Period 1, Treatment B in Period 2, and Treatment A in Period 3 |
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| Part II - Sequence DEF | Experimental | Treatment D in Period 1, Treatment E in Period 2, and Treatment F in Period 3 |
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| Part II - Sequence DFE | Experimental | Treatment D in Period 1, Treatment F in Period 2, and Treatment E in Period 3 |
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| Part II - Sequence EFD | Experimental | Treatment E in Period 1, Treatment F in Period 2, and Treatment D in Period 3 |
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| Part II - Sequence EDF | Experimental | Treatment E in Period 1, Treatment D in Period 2, and Treatment F in Period 3 |
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| Part II - Sequence FDE | Experimental | Treatment F in Period 1, Treatment D in Period 2, and Treatment E in Period 3 |
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| Part II -Sequence FED | Experimental | Treatment F in Period 1, Treatment E in Period 2, and Treatment D in Period 3 |
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| Treatment B | Drug | MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266. |
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| Treatment C | Drug | Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266. |
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| Treatment D | Drug | MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266. |
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| Treatment E | Drug | MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266. |
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| Treatment F | Drug | Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266. |
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| Predose and 2, 4, and 8 hours after dosing on Day 4 of each period |
| Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 1 and Day 3 | The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 1 and Day 3. | Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3 |
| Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 4 | The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 4. | Predose and 2, 4, and 8 hours after dosing on Day 4 of each period |
| Change From Baseline in Heart Rate (HR) | The effect of MK-8266 and placebo on changes in HR were assessed, as measured by time weighted average change from baseline in HR over 0-24 hours postdose (TWA^0-24 hr) on Day 3. Baseline values for HR are shown in the Baseline Characteristics section. | Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3 |
| Change From Baseline in Diastolic Blood Pressure (DBP) | The effect of MK-8266 and placebo on changes in diastolic blood pressure (DBP) were assessed, as measured by time weighted average change from baseline in DBP over 0-24 hours postdose (TWA^0-24 hr) on Day 3. Baseline values for DBP are shown in the Baseline Characteristics section. | Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3 |
| FG002 | Sequence BCA | MK-8266 0.9 mg FDD, then Placebo, then MK-8266 1.3 mg BID |
| FG003 | Sequence BAC | MK-8266 0.9 mg FDD, then MK-8266 1.3 mg BID, then Placebo |
| FG004 | Sequence CAB | Placebo, then MK-8266 1.3 mg BID, then MK-8266 0.9 mg FDD |
| FG005 | Sequence CBA | Placebo, then MK-8266 0.9 mg FDD, then MK-8266 1.3 mg BID |
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| COMPLETED |
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| NOT COMPLETED |
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| Part 1: Period 2 |
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| Part 1: Period 3 |
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This was a 3-period crossover study, with a total of 31 randomized participants at Baseline in Sequences A, B, and C.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants, All Sequences | A: MK-8266 1.3 mg BID, B: MK-8266 0.9 mg FDD, C: Placebo |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Total of 31 participants in Sequences A, B, and C | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Heart Rate (HR) | HR summary for the enrolled population | All participants who were randomized to receive study treatment and had HR measurement | Mean | Standard Deviation | Beats per minute |
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| Diastolic Blood Pressure (DBP) | DBP summary for the enrolled population | All participants who were randomized to receive study treatment and had DBP measurement | Mean | Standard Deviation | mmHg |
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| 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 | Adverse Events (AEs) | The number of participants with one or more clinical or laboratory AEs was assessed. 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. | All participants who received at least one dose of study treatment | Posted | Count of Participants | Participants | MK-8266 1.3 mg BID and 0.9 mg FDD groups: Up to Day 4 in each period; MK-8266 1 mg QD group: the last AE was reported on day 10 after the last dose; Placebo group: Up to 10-14 days after the last dose of placebo |
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| Primary | Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Days 1 and 3 | The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided. | All participants who received at least one dose of the investigational drug and had assessment of AUC(0-8 hours) | Posted | Mean | Standard Deviation | nM*hr | Pre-dose and 0.5, 1, 2, 4, and 8 hours after dosing on Day 1, and pre-dose and 4 and 8 hours after dosing on Day 3 of each period |
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| Primary | Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Day 4 | The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided. | All participants who received at least one dose of the investigational drug and had assessment of AUC(0-8 hours) | Posted | Mean | Standard Deviation | nM*hr | Predose and 2, 4, and 8 hours after dosing on Day 4 of each period |
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| Primary | Maximum Plasma Concentration (Cmax) of MK-8266 on Day 1 and Day 3 | The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided. | All participants who received at least one dose of the investigational drug and had assessment for Cmax | Posted | Mean | Standard Deviation | mg/mL | Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3 |
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| Primary | Maximum Plasma Concentration (Cmax) of MK-8266 on Day 4 | The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided. | All participants who received at least one dose of the investigational drug and had assessment for Cmax | Posted | Mean | Standard Deviation | nM | Predose and 2, 4, and 8 hours after dosing on Day 4 of each period |
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| Primary | Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 1 and Day 3 | The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 1 and Day 3. | All participants who received at least one dose of the investigational drug and had assessment for Tmax | Posted | Median | Full Range | Hours | Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3 |
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| Primary | Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 4 | The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 4. | All participants who received at least one dose of the investigational drug and had assessment for Tmax | Posted | Median | Full Range | Hours | Predose and 2, 4, and 8 hours after dosing on Day 4 of each period |
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| Primary | Change From Baseline in Heart Rate (HR) | The effect of MK-8266 and placebo on changes in HR were assessed, as measured by time weighted average change from baseline in HR over 0-24 hours postdose (TWA^0-24 hr) on Day 3. Baseline values for HR are shown in the Baseline Characteristics section. | All participants who received at least one dose of the investigational drug and had HR measurements | Posted | Least Squares Mean | Standard Deviation | Beats per minute | Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3 |
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| Primary | Change From Baseline in Diastolic Blood Pressure (DBP) | The effect of MK-8266 and placebo on changes in diastolic blood pressure (DBP) were assessed, as measured by time weighted average change from baseline in DBP over 0-24 hours postdose (TWA^0-24 hr) on Day 3. Baseline values for DBP are shown in the Baseline Characteristics section. | All participants who received at least one dose of the investigational drug and had DBP measurements. | Posted | Least Squares Mean | Standard Deviation | mmHg | Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3 |
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MK-8266 1.3 mg BID and 0.9 mg FDD groups: Up to Day 4 in each period; MK-8266 1 mg QD group: the last AE is reported on day 10 after the last dose; Placebo group: Up to 10-14 days after the last dose of placebo
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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) |
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| EG000 | MK-8266 1.3 mg BID | MK-8266 administered as 1.0 mg in the morning + 0.3 mg 8 hours later on Days 1, 2, and 3 | 0 | 25 | 0 | 25 | 9 | 25 |
| EG001 | MK-8266 0.9 mg FDD | MK-8266 administered as 0.1 mg every 2 hours on Days 1, 2, and 3 | 0 | 26 | 0 | 26 | 16 | 26 |
| EG002 | MK-8266 1 mg QD | MK-8266 administered a single 1 mg dose on Day 4 | 0 | 26 | 0 | 26 | 8 | 26 |
| EG003 | Placebo | Placebo matching MK-8266 administered on Days 1, 2, 3 and 4 | 0 | 27 | 0 | 27 | 9 | 27 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Accelerated idioventricular rhythm | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Epigastric discomfort | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Paraesthesia oral | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Vessel puncture site inflammation | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Open wound | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
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| Blood pressure diastolic increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Blood pressure systolic increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Sensation of heaviness | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Disturbance in attention | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Hemicephalalgia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Hyperaesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Nervousness | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Micturition urgency | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
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| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
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| C494814 | BID protein, human |
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