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A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01798849
Recruitment Status : Completed
First Posted : February 26, 2013
Results First Posted : July 22, 2019
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Interventions Drug: MK-8892
Drug: Placebo for MK-8892
Enrollment 25
Recruitment Details  
Pre-assignment Details In Panels A and B, 8 healthy male participants alternately received single rising doses of MK-8892 or placebo.In Panel C, 8 mild to moderate hypertensive male participants received single rising doses of MK-8892 determined by results of Panels A and B or placebo. Each period in a panel was separated by a 7-day washout.
Arm/Group Title Panel A-Healthy Panel B-Healthy Panel C-Mild/Moderate Hypertension
Hide Arm/Group Description Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, or 14 mg, and 2 participants received placebo. Dosing periods alternated with Panel B. Within each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods alternated with Panel A. Within each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages were determined by the results of Panels A and B.
Period Title: Overall Study
Started 8 8 9 [1]
Completed 8 8 8
Not Completed 0 0 1
Reason Not Completed
Physician Decision             0             0             1
[1]
1 participant discontinued after Period 1 and was replaced for Periods 2-4
Arm/Group Title Panel A-Healthy Panel B-Healthy Panel C-Mild/Moderate Hypertension Total
Hide Arm/Group Description Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, or 14 mg, and 2 participants received placebo. Dosing periods alternated with Panel B. Within each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods alternated with Panel A. Within each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages were determined by the results of Panels A and B. Total of all reporting groups
Overall Number of Baseline Participants 8 8 9 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 8 participants 9 participants 25 participants
42.8  (9.5) 37.1  (15.1) 50.6  (5.3) 43.8  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 8 participants 9 participants 25 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
8
 100.0%
8
 100.0%
9
 100.0%
25
 100.0%
1.Primary Outcome
Title Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants
Hide Description An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Time Frame up to 7 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All healthy participants (Panels A and B) who received at least 1 dose of the study drug. As pre-specified in the protocol, safety data were pooled for the MK 8892 2.0 mg fed and fasted arms only and were not planned to be provided separately.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy (Pooled) 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 16
Measure Type: Number
Unit of Measure: Percentage of Participants
50.0 66.7 50.0 100.0 100.0 83.3 100.0 100.0 43.8
2.Primary Outcome
Title Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants
Hide Description An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Time Frame up to 7 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All healthy participants (Panels A and B) who received at least 1 dose of the study drug. As pre-specified in the protocol, safety data were pooled for the MK 8892 2.0 mg fed and fasted arms only and were not planned to be provided separately.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy (Pooled) 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 16
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
3.Primary Outcome
Title Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants
Hide Description Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Time Frame Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels A and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 16
Least Squares Mean (Standard Error)
Unit of Measure: mm Hg
-1.83  (1.71) -2.27  (1.69) -4.21  (1.70) -4.25  (1.71) -6.22  (1.70) -6.64  (1.69) -6.94  (1.69) -8.89  (1.70) -1.33  (1.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.732
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in Least-square (LS) Means
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-3.42 to 2.43
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.531
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.94
Confidence Interval (2-Sided) 95%
-3.94 to 2.06
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.056
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS Means
Estimated Value -2.88
Confidence Interval (2-Sided) 95%
-5.83 to 0.08
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 4.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.92
Confidence Interval (2-Sided) 95%
-6.00 to 0.17
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -4.89
Confidence Interval (2-Sided) 95%
-7.79 to -1.99
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 9.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -5.31
Confidence Interval (2-Sided) 95%
-8.32 to -2.31
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 12.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -5.61
Confidence Interval (2-Sided) 95%
-8.62 to -2.60
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 14.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -7.56
Confidence Interval (2-Sided) 95%
-10.50 to -4.63
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
4.Primary Outcome
Title Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants
Hide Description An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Time Frame up to 7 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All hypertensive participants (Panel C) who received at least 1 dose of the study drug in a fasted state.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892. Includes rechallenge
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 9 8
Measure Type: Number
Unit of Measure: Percentage of Participants
50.0 33.3 66.7 77.8 75.0
5.Primary Outcome
Title Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants
Hide Description An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Time Frame up to 7 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All hypertensive participants (Panel C) who received at least 1 dose of the study drug in a fasted state.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892. Includes rechallenge
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 9 8
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 0.0 0.0 0.0 0.0
6.Primary Outcome
Title Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants
Hide Description Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Time Frame Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period)
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 8
Least Squares Mean (Standard Error)
Unit of Measure: mm Hg
-3.56  (1.87) -4.76  (1.85) -7.55  (1.85) -7.86  (1.59) -1.22  (1.67)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.165
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.34
Confidence Interval (2-Sided) 95%
-5.70 to 1.02
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -3.53
Confidence Interval (2-Sided) 95%
-6.86 to -0.21
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.000
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -6.32
Confidence Interval (2-Sided) 95%
-9.55 to -3.10
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -6.63
Confidence Interval (2-Sided) 95%
-9.35 to -3.92
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
7.Secondary Outcome
Title Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants
Hide Description Peripheral diastolic blood pressure was measured using a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Time Frame Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 16
Least Squares Mean (Standard Error)
Unit of Measure: mm Hg
-4.34  (1.73) -2.43  (0.83) -3.69  (1.10) -4.50  (1.49) -6.56  (1.06) -7.04  (0.99) -7.35  (0.71) -9.89  (1.68) -1.67  (0.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.67
Confidence Interval (2-Sided) 95%
-6.14 to 0.80
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.305
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.76
Confidence Interval (2-Sided) 95%
-2.24 to 0.72
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.070
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.03
Confidence Interval (2-Sided) 95%
-4.23 to 0.17
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 4.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.84
Confidence Interval (2-Sided) 95%
-5.48 to -0.19
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -4.89
Confidence Interval (2-Sided) 95%
-6.40 to -3.37
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 9.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effects model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -5.37
Confidence Interval (2-Sided) 95%
-7.29 to -3.46
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 12.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -5.68
Confidence Interval (2-Sided) 95%
-6.70 to -4.65
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 14.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -8.22
Confidence Interval (2-Sided) 95%
-11.95 to -4.50
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
8.Secondary Outcome
Title Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants
Hide Description Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Time Frame Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 16
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
0.46  (1.36) 5.55  (1.32) 4.71  (1.42) 7.44  (1.93) 9.29  (2.22) 8.85  (1.93) 10.34  (1.09) 16.29  (2.21) 2.23  (1.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.212
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -1.77
Confidence Interval (2-Sided) 95%
-4.59 to 1.05
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 3.32
Confidence Interval (2-Sided) 95%
0.00 to 6.64
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method Mixed effect model
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
0.49 to 4.47
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 4.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 5.21
Confidence Interval (2-Sided) 95%
1.51 to 8.92
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 7.06
Confidence Interval (2-Sided) 95%
3.03 to 11.10
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 9.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 6.62
Confidence Interval (2-Sided) 95%
2.54 to 10.71
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 12.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 8.11
Confidence Interval (2-Sided) 95%
5.45 to 10.76
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 14.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 14.05
Confidence Interval (2-Sided) 95%
10.54 to 17.57
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
9.Secondary Outcome
Title Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants
Hide Description AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours.
Time Frame Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel)
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 6 6 6 6 16
Least Squares Mean (Standard Error)
Unit of Measure: Percentage
-1.73  (2.30) -2.31  (2.32) -2.82  (2.31) -0.26  (2.38) -4.23  (2.29) -3.85  (2.31) -1.84  (2.30) -4.81  (2.32) -0.07  (2.06)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.202
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -1.66
Confidence Interval (2-Sided) 95%
-4.24 to 0.93
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.115
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.23
Confidence Interval (2-Sided) 95%
-5.03 to 0.57
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.75
Confidence Interval (2-Sided) 95%
-5.40 to -0.09
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 4.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.901
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-3.22 to 2.84
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Mixed effect model
Estimated Value -4.15
Confidence Interval (2-Sided) 95%
-6.74 to -1.57
Estimation Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 9.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -3.77
Confidence Interval (2-Sided) 95%
-6.48 to -1.06
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 12.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.201
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -1.77
Confidence Interval (2-Sided) 95%
-4.51 to 0.98
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 14.0 mg MK-8892-Healthy, Placebo-Healthy
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -4.74
Confidence Interval (2-Sided) 95%
-7.37 to -2.11
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
10.Secondary Outcome
Title Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants
Hide Description Peripheral blood pressure assessments were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose by using a validated automatic measuring device. Peripheral diastolic blood pressure was measured a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.
Time Frame Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 8
Least Squares Mean (Standard Error)
Unit of Measure: mm Hg
-3.40  (1.13) -4.17  (1.63) -7.29  (1.40) -9.16  (1.43) -0.87  (1.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.042
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.53
Confidence Interval (2-Sided) 95%
-4.97 to -0.10
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -3.29
Confidence Interval (2-Sided) 95%
-5.71 to -0.88
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -6.42
Confidence Interval (2-Sided) 95%
-8.94 to -3.89
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -8.28
Confidence Interval (2-Sided) 95%
-11.32 to -5.25
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
11.Secondary Outcome
Title Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants
Hide Description Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.
Time Frame Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 8
Least Squares Mean (Standard Error)
Unit of Measure: bpm
-0.92  (1.59) -0.74  (1.88) 0.87  (1.92) 7.68  (1.51) -1.46  (1.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.638
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
-1.80 to 2.87
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.616
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
-2.20 to 3.63
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 2.33
Confidence Interval (2-Sided) 95%
0.11 to 4.56
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 9.14
Confidence Interval (2-Sided) 95%
6.98 to 11.30
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
12.Secondary Outcome
Title TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants
Hide Description AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.
Time Frame Predose to 24 hours Postdose (for each Dosing Period of Each Panel)
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of placebo to match MK-8892
Overall Number of Participants Analyzed 6 6 6 6 8
Least Squares Mean (Standard Error)
Unit of Measure: Percentage
-2.30  (2.01) -2.57  (2.01) -3.94  (2.01) -5.43  (1.80) -1.65  (1.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.5 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.677
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-3.81 to 2.52
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.554
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-4.08 to 2.24
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 2.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.137
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.29
Confidence Interval (2-Sided) 95%
-5.35 to 0.78
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 6.0 mg MK-8892-Hypertensive, Placebo-Hypertensive
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Mixed effect model
Comments Mixed effects model for each cohort containing fixed effects for Day 1 predose and treatment and a random effect for participant.
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -3.78
Confidence Interval (2-Sided) 95%
-6.37 to -1.19
Estimation Comments Difference in LS means = LS mean MK-8892 minus LS mean placebo
13.Secondary Outcome
Title Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Healthy Participants
Hide Description Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr.
Time Frame Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Overall Number of Participants Analyzed 6 5 6 6 5 6 6 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM·hr
67
(27%)
128
(32%)
218
(11%)
464
(28%)
694
(14%)
793
(31%)
1202
(25%)
1306
(18%)
14.Secondary Outcome
Title Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Healthy Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Overall Number of Participants Analyzed 6 5 6 6 5 6 6 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM·hr
103.3
(40.0%)
216.8
(58.7%)
368.5
(29.2%)
724.7
(42.9%)
1157.6
(26.4%)
1293.3
(39.4%)
2286.3
(35.7%)
2527.7
(25.5%)
15.Secondary Outcome
Title Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892 - Healthy Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Overall Number of Participants Analyzed 6 5 6 6 5 6 6 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM·hr
113
(37%)
232
(63%)
391
(34%)
757
(50%)
1195
(30%)
1342
(41%)
2443
(39%)
2702
(31%)
16.Secondary Outcome
Title Maximum Concentration (Cmax) of MK-8892 - Healthy Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Overall Number of Participants Analyzed 6 5 6 6 5 6 6 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
4.8
(32%)
8.5
(23%)
17.9
(19%)
35.6
(26%)
49.0
(21%)
52.8
(38%)
72.8
(23%)
87.3
(16%)
17.Secondary Outcome
Title Time to Cmax (Tmax) of MK-8892 - Healthy Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Overall Number of Participants Analyzed 6 5 6 6 5 6 6 5
Median (Full Range)
Unit of Measure: hours
4
(2 to 6)
4
(1 to 6)
4
(1 to 6)
4
(1 to 6)
4
(2 to 6)
5
(4 to 8)
4
(4 to 8)
2
(1 to 8)
18.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of MK-8892 - Healthy Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panels and B) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
Single oral dose of 2.0 mg MK-8892
Single oral dose of 4.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Single oral dose of 9.0 mg MK-8892
Single oral dose of 12.0 mg MK-8892
Single oral dose of 14.0 mg MK-8892
Overall Number of Participants Analyzed 6 5 6 6 5 6 6 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
17.9
(28%)
20.6
(40%)
20.1
(44%)
17.7
(43%)
15.6
(45%)
20.9
(28%)
23.7
(23%)
21.1
(41%)
19.Secondary Outcome
Title Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Hypertensive Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Includes protocol-defined 6.0 mg rechallenge.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive - Rechallenge
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Participants who were assigned to 6.0 mg HT group who were administered a rechallenge 6.0 mg dose of MK-8892
Overall Number of Participants Analyzed 6 6 6 5 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM·hr
79
(27%)
158
(14%)
285
(17%)
806
(24%)
714
(22%)
20.Secondary Outcome
Title Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Hypertensive Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive - Rechallenge
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Participants who were assigned to 6.0 mg HT group who were administered a rechallenge 6.0 mg dose of MK-8892
Overall Number of Participants Analyzed 6 6 6 5 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM·hr
150.2
(45.9%)
317.3
(25.9%)
522.3
(24.0%)
1700.2
(38.5%)
1538.8
(23.5%)
21.Secondary Outcome
Title Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892- Hypertensive Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Includes protocol-defined 6.0 mg rechallenge.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive - Rechallenge
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Participants who were assigned to 6.0 mg HT group who were administered a rechallenge 6.0 mg dose of MK-8892
Overall Number of Participants Analyzed 6 6 6 5 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM·hr
164.0
(53.0%)
346.0
(32.0%)
557.0
(28.0%)
1947.0
(48.0%)
1760.0
(38.0%)
22.Secondary Outcome
Title Maximum Concentration (Cmax) of MK-8892- Hypertensive Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Includes protocol-defined 6.0 mg rechallenge.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive - Rechallenge
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Participants who were assigned to 6.0 mg HT group who were administered a rechallenge 6.0 mg dose of MK-8892
Overall Number of Participants Analyzed 6 6 6 5 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM
4.9
(21.0%)
9.8
(13.0%)
17.6
(30.0%)
48.9
(15.0%)
47.1
(33.0%)
23.Secondary Outcome
Title Time to Cmax (Tmax) of MK-8892- Hypertensive Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Includes protocol-defined 6.0 mg rechallenge.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive - Rechallenge
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Participants who were assigned to 6.0 mg HT group who were administered a rechallenge 6.0 mg dose of MK-8892
Overall Number of Participants Analyzed 6 6 6 5 6
Median (Full Range)
Unit of Measure: Hours
3
(1 to 6)
4
(2 to 8)
6
(4 to 12)
4
(2 to 12)
4
(4 to 8)
24.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of MK-8892- Hypertensive Participants
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Hypertensive participants (Panel C) who were administered study drug in a fasted state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint. Includes protocol-defined 6.0 mg rechallenge.
Arm/Group Title 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive - Rechallenge
Hide Arm/Group Description:
Single oral dose of 0.5 mg MK-8892
Single oral dose of 1.0 mg MK-8892
single oral dose of 2.0 mg MK-8892
Single oral dose of 6.0 mg MK-8892
Participants who were assigned to 6.0 mg HT group who were administered a rechallenge 6.0 mg dose of MK-8892
Overall Number of Participants Analyzed 6 6 6 5 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours
23.5
(30%)
24.5
(28%)
21.6
(34%)
28.8
(49%)
26.3
(57%)
25.Secondary Outcome
Title Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of 2.0 mg MK-8892-Healthy Participants-Fasted/Fed
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panel A) who were administered 2.0 mg MK-8892 in both fasted and fed state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 2.0 mg MK-8892-Healthy-Fasted 2.0 mg MK-8892-Healthy-Fed
Hide Arm/Group Description:
Single oral dose of 2.0 mg MK-8892 after an 8-hour fast
Single oral dose of 2.0 mg MK-8892 after a high-fat breakfest
Overall Number of Participants Analyzed 6 6
Geometric Mean (90% Confidence Interval)
Unit of Measure: nM·hr
218.2
(199.3 to 238.9)
278.2
(241.5 to 320.4)
26.Secondary Outcome
Title Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panel A) who were administered 2.0 mg MK-8892 in both fasted and fed state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 2.0 mg MK-8892-Healthy-Fasted 2.0 mg MK-8892-Healthy-Fed
Hide Arm/Group Description:
Single oral dose of 2.0 mg MK-8892 after an 8-hour fast
Single oral dose of 2.0 mg MK-8892 after a high-fat breakfest
Overall Number of Participants Analyzed 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nM·hr
368.5
(29.2%)
494.6
(29.2%)
27.Secondary Outcome
Title Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panel A) who were administered 2.0 mg MK-8892 in both fasted and fed state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 2.0 mg MK-8892-Healthy-Fasted 2.0 mg MK-8892-Healthy-Fed
Hide Arm/Group Description:
Single oral dose of 2.0 mg MK-8892 after an 8-hour fast
Single oral dose of 2.0 mg MK-8892 after a high-fat breakfest
Overall Number of Participants Analyzed 6 6
Geometric Mean (90% Confidence Interval)
Unit of Measure: nM·hr
390.0
(298.7 to 509.1)
518.5
(400.6 to 671.1)
28.Secondary Outcome
Title Maximum Concentration (Cmax) of 2.0 mg MK-8892 - Healthy Participants- Fasted/Fed
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panel A) who were administered 2.0 mg MK-8892 in both fasted and fed state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 2.0 mg MK-8892-Healthy-Fasted 2.0 mg MK-8892-Healthy-Fed
Hide Arm/Group Description:
Single oral dose of 2.0 mg MK-8892 after an 8-hour fast
Single oral dose of 2.0 mg MK-8892 after a high-fat breakfest
Overall Number of Participants Analyzed 6 6
Geometric Mean (90% Confidence Interval)
Unit of Measure: nM
17.9
(15.3 to 20.9)
20.5
(17.8 to 23.6)
29.Secondary Outcome
Title Apparent Terminal Half-life (t1/2) of 2.0 mg MK-8892 - Healthy Participants -Fasted/Fed
Hide Description Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Time Frame Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Healthy participants (Panel A) who were administered 2.0 mg MK-8892 in both fasted and fed state, who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of the treatment, according to the underlying scientific model and had data available for endpoint.
Arm/Group Title 2.0 mg MK-8892-Healthy -Fasted 2.0 Mg MK-8892- Healthy - Fed
Hide Arm/Group Description:
Single oral dose of 2.0 mg MK-8892 after an 8-hour fast
single oral dose of 2.0 mg MK-8892 after a high-fat breakfest
Overall Number of Participants Analyzed 6 6
Geometric Mean (90% Confidence Interval)
Unit of Measure: Hours
20.1
(14.3 to 28.5)
20.5
(17.3 to 24.2)
Time Frame up to 7 weeks
Adverse Event Reporting Description All participants who received at least 1 dose of the study drug. Adverse events are reported by dose taken at time of event and not by panel or sequence. As pre-specified in the protocol, safety data were pooled for the MK 8892 2.0 mg fed and fasted arms only and were not planned to be provided separately.
 
Arm/Group Title 0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy (Pooled) 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Hide Arm/Group Description Single oral dose of 0.5 mg MK-8892 Single oral dose of 1.0 mg MK-8892 Single oral dose of 2.0 mg MK-8892. Single oral dose of 4.0 mg MK-8892 Single oral dose of 6.0 mg MK-8892 Single oral dose of 9.0 mg MK-8892 Single oral dose of 12.0 mg MK-8892 Single oral dose of 14.0 mg MK-8892 Single oral dose of placebo to match MK-8892 Single oral dose of 0.5 mg MK-8892 Single oral dose of 1.0 mg MK-8892 Single oral dose of 2.0 mg MK-8892 Single oral dose of 6.0 mg MK-8892. Includes rechallenge Single oral dose of placebo to match MK-8892
All-Cause Mortality
0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy (Pooled) 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/16 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/9 (0.00%)      0/8 (0.00%)    
Hide Serious Adverse Events
0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy (Pooled) 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/16 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/9 (0.00%)      0/8 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
0.5 mg MK-8892-Healthy 1.0 mg MK-8892-Healthy 2.0 mg MK-8892-Healthy (Pooled) 4.0 mg MK-8892-Healthy 6.0 mg MK-8892-Healthy 9.0 mg MK-8892-Healthy 12.0 mg MK-8892-Healthy 14.0 mg MK-8892-Healthy Placebo-Healthy 0.5 mg MK-8892-Hypertensive 1.0 mg MK-8892-Hypertensive 2.0 mg MK-8892-Hypertensive 6.0 mg MK-8892-Hypertensive Placebo-Hypertensive
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/6 (50.00%)      4/6 (66.67%)      3/6 (50.00%)      6/6 (100.00%)      6/6 (100.00%)      5/6 (83.33%)      6/6 (100.00%)      6/6 (100.00%)      7/16 (43.75%)      3/6 (50.00%)      2/6 (33.33%)      4/6 (66.67%)      7/9 (77.78%)      6/8 (75.00%)    
Cardiac disorders                             
Palpitations †  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/6 (33.33%)  2 0/16 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0
Postural orthostatic tachycardia syndrome †  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Ear and labyrinth disorders                             
Tinnitus †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Gastrointestinal disorders                             
Abdominal discomfort †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Abdominal distension †  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Abdominal pain †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Change of bowel habit †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  2
Constipation †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Dyspepsia †  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Loose stools †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Nausea †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 1/9 (11.11%)  1 2/8 (25.00%)  2
Vomiting †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
General disorders                             
Chest pain †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Cyst †  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Fatigue †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  2 3/16 (18.75%)  4 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/9 (0.00%)  0 1/8 (12.50%)  2
Feeling hot †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Oedema peripheral †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Infections and infestations                             
Common cold †  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 2/16 (12.50%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Oral herpes †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Injury, poisoning and procedural complications                             
Lower limb wound †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Open wound †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Upper limb wound †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Investigations                             
Blood pressure systolic decreased †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/16 (6.25%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  2 2/9 (22.22%)  3 0/8 (0.00%)  0
Blood pressure systolic increased †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Metabolism and nutrition disorders                             
Decreased appetite †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 1/8 (12.50%)  1
Musculoskeletal and connective tissue disorders                             
Back pain †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Back pain (with radiation) †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Flank pain †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Musculoskeletal chest pain †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Musculoskeletal pain †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Pain in arm †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Shoulder pain †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Nervous system disorders                             
Dizziness †  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Dizziness postural †  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Headache †  2/6 (33.33%)  2 3/6 (50.00%)  3 1/6 (16.67%)  2 5/6 (83.33%)  6 4/6 (66.67%)  4 3/6 (50.00%)  4 6/6 (100.00%)  9 4/6 (66.67%)  6 0/16 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  2 2/6 (33.33%)  2 5/9 (55.56%)  6 4/8 (50.00%)  7
Presyncope †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Renal and urinary disorders                             
Polyuria †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0
Urine odour abnormal †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                             
Bronchial hyperreactivity †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Cough †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Dyspnoea †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Nasal congestion †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Skin and subcutaneous tissue disorders                             
Eczema †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/16 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Skin irritation †  0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Urtication †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/16 (6.25%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0
Vascular disorders                             
Haematoma †  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)