Trial Outcomes & Findings for A Multiple Dose Study of MK-3614 (MK-3614-002) (NCT NCT01033643)
NCT ID: NCT01033643
Last Updated: 2021-05-03
Results Overview
An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study intervention, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study intervention, was also an adverse event. The number of participants who experienced an AE was reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
Up to approximately 27 days
Results posted on
2021-05-03
Participant Flow
All 30 participants randomized to the study, received at least one dose of study treatment (All Treated Population) and were evaluable for all safety analysis. No participants were enrolled in Panel E.
Participant milestones
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
MK-3614 0.50 mg (Panel E)
Participants were to receive 0.50 mg BID every 12 hours apart or a matching placebo on Day 1 followed by 3 doses (0.50/0.50/0.25 mg) of MK-3614 each 8 hours apart on Day 2, three doses of 0.50 mg of MK-3614 8 hours apart on Days 3, 4 and 0.75 mg of MK-3614 BID every 12 hours on Days 5-14. No participants were enrolled in this group.
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
4
|
0
|
8
|
|
Overall Study
COMPLETED
|
6
|
3
|
6
|
4
|
0
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
MK-3614 0.50 mg (Panel E)
Participants were to receive 0.50 mg BID every 12 hours apart or a matching placebo on Day 1 followed by 3 doses (0.50/0.50/0.25 mg) of MK-3614 each 8 hours apart on Day 2, three doses of 0.50 mg of MK-3614 8 hours apart on Days 3, 4 and 0.75 mg of MK-3614 BID every 12 hours on Days 5-14. No participants were enrolled in this group.
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrew Consent
|
0
|
3
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Multiple Dose Study of MK-3614 (MK-3614-002)
Baseline characteristics by cohort
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=8 Participants
Participants received a dose matched placebo orally according to randomization.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
49.7 Years
STANDARD_DEVIATION 5.4 • n=5 Participants
|
48.8 Years
STANDARD_DEVIATION 2.1 • n=7 Participants
|
49.2 Years
STANDARD_DEVIATION 6.1 • n=5 Participants
|
49.3 Years
STANDARD_DEVIATION 8.2 • n=4 Participants
|
45.0 Years
STANDARD_DEVIATION 5.7 • n=21 Participants
|
48.1 Years
STANDARD_DEVIATION 3.6 • n=8 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
30 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
30 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
30 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 27 daysPopulation: All participants who received at least one dose of the study treatment. No participants were enrolled in Panel E.
An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study intervention, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study intervention, was also an adverse event. The number of participants who experienced an AE was reported.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=8 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Number of Participants Who Experienced an Adverse Event (AE)
|
4 Participants
|
3 Participants
|
4 Participants
|
3 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 13 daysPopulation: All participants who received at least one dose of the study treatment. No participants were enrolled in Panel E.
An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study intervention, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study intervention, was also an adverse event. The number of participants who discontinued study treatment due to an AE was reported.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=8 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Number of Participants Who Discontinued Study Treatment Due to an AE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Days 1, 10: Predose and 1, 2, 4, 6, 8 & 12 hours postdosePopulation: All participants in Panel A who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the AUC 0-12hrs were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at pre-specified timepoints on first day of multiple dosing of MK-3614 (Day 1) and last day of multiple dosing of MK-3614 (Day 10) to determine the AUC 0-12hrs of MK-3614 in Panel A participants per protocol. AUC 0-12hrs was defined as the area under the concentration-time curve of MK-3614 from time zero to 12 hours postdose.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel A: Area Under the Concentration Time-Curve From 0 to 12 Hours (AUC 0-12hrs) of MK-3614
First Day (Day 1)
|
43.9 nM*hr
Standard Deviation 8.62
|
—
|
—
|
—
|
—
|
|
Panel A: Area Under the Concentration Time-Curve From 0 to 12 Hours (AUC 0-12hrs) of MK-3614
Last Day (Day 10)
|
105.0 nM*hr
Standard Deviation 24.4
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 4, 13: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8 & 12 hours postdosePopulation: All participants in Panel D who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for AUC 0-12hrs were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at pre-specified timepoints to determine the AUC 0-12hrs on first day of multiple dosing of MK-3614 (Day 4) and last day of multiple dosing of MK-3614 (Day 13) to determine the AUC 0-12hrs of MK-3614 in Panel D participants per protocol. AUC 0-12hrs was defined as the area under the concentration-time curve of MK-3614 from time zero to 12 hours postdose.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel D: Area Under the Concentration Time-Curve From 0 to 12 Hours (AUC 0-12hrs) of MK-3614
First Day (Day 4)
|
—
|
—
|
—
|
87.8 nM*hr
Standard Deviation 11.0
|
—
|
|
Panel D: Area Under the Concentration Time-Curve From 0 to 12 Hours (AUC 0-12hrs) of MK-3614
Last Day (Day 13)
|
—
|
—
|
—
|
144.0 nM*hr
Standard Deviation 28.1
|
—
|
PRIMARY outcome
Timeframe: Day 1: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 14, & 24 hours postdosePopulation: All participants in Panel D who received single day dose of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the AUC 0-inf. No participants were enrolled in Panel E.
Blood samples were collected at pre-specified timepoints to determine the AUC 0-inf of MK-3614 in Panel D participants who received single daily dosing on Day 1. AUC 0-inf was defined as the area under the concentration-time curve of MK-3614 from time zero to infinity. Geometric mean and 95%CI were not reported because the single day dosing of MK-3614 was only administered on Day 1 for Panel D participants. Instead, AUC 0-24 hours was reported for Panel D participants on Day 1 which is included in the 'other pre-specified outcomes'.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Days 1, 10: Predose and 1, 2, 4, 6, 8, 12, 16, & 24 hours postdosePopulation: All participants in Panel B \& C who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for AUC 0-24hrs were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at pre-specified timepoints to determine the AUC 0-24hrs on first day of multiple dosing of MK-3614 (Day 1) and last day of multiple dosing of MK-3614 (Day 10) to determine the AUC 0-24hrs of MK-3614 in Panel B \& C participants per protocol. AUC0-24hrs was defined as the area under the concentration-time curve of MK-3614 from time zero to 24 hours postdose.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panels B, C: Area Under the Concentration Time-Curve From 0 to 24 Hours (AUC 0-24hrs) of MK-3614
First Day (Day 1)
|
—
|
188.0 nM*hr
Standard Deviation 46.7
|
190.0 nM*hr
Standard Deviation 72.3
|
—
|
—
|
|
Panels B, C: Area Under the Concentration Time-Curve From 0 to 24 Hours (AUC 0-24hrs) of MK-3614
Last Day (Day 10)
|
—
|
335.0 nM*hr
Standard Deviation 66.1
|
302.0 nM*hr
Standard Deviation 82.3
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 1, 10: Predose and 1, 2, 4, 6, 8 & 12 hours postdosePopulation: All participants in Panel A who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the Cmax were evaluated. No participants were enrolled in Panel E.
Blood samples were collected predose and up to 12 hours postdose on first day of multiple dosing of MK-3614 (Day 1) and last day of multiple dosing (Day 10) for the determination of Cmax in Panel A participants. Cmax was defined as the maximum concentration of MK-3614 reached over 12 hours.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel A: Maximum Concentration (Cmax) of MK-3614
First Day (Day 1)
|
5.61 nM
Standard Deviation 1.22
|
—
|
—
|
—
|
—
|
|
Panel A: Maximum Concentration (Cmax) of MK-3614
Last Day (Day 10)
|
11.6 nM
Standard Deviation 2.33
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 4, 13: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, & 12 hours postdosePopulation: All participants in Panel D who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the Cmax were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at predose and up to 12 hours postdose on first day of multiple dosing of MK-3614 (Day 4) and last day of multiple dosing of MK-3614 (Day 13) for the determination of Cmax in Panel D participants. Cmax was defined as the maximum concentration of MK-3614 reached over 12 hours after administration of multiple doses of MK-3614.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel D: Maximum Concentration (Cmax) of MK-3614
First Day (Day 4)
|
—
|
—
|
—
|
11.6 nM
Standard Deviation 0.85
|
—
|
|
Panel D: Maximum Concentration (Cmax) of MK-3614
Last Day (Day 13)
|
—
|
—
|
—
|
16.1 nM
Standard Deviation 3.04
|
—
|
PRIMARY outcome
Timeframe: Days 1, 10: Predose and 1, 2, 4, 6, 8, 12, 16, & 24 hours postdosePopulation: All participants in Panels B, C who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the Cmax were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at predose and up to 24 hours postdose on first day of multiple dosing of MK-3614 (Day 1) and last day of multiple dosing of MK-3614 (Day 10) for the determination of Cmax in Panel B \& C participants. Cmax was defined as the maximum concentration of MK-3614 reached over 24 hours.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panels B, C: Maximum Concentration (Cmax) of MK-3614
First Day (Day 1)
|
—
|
12.2 nM
Standard Deviation 1.95
|
11.1 nM
Standard Deviation 3.67
|
—
|
—
|
|
Panels B, C: Maximum Concentration (Cmax) of MK-3614
Last Day (Day 10)
|
—
|
19.0 nM
Standard Deviation 3.92
|
18.5 nM
Standard Deviation 4.92
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 1, 10: Predose and 1, 2, 4, 6, 8, & 12 hours postdosePopulation: All participants in Panel A who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the Tmax were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at predose and up to 12 hours postdose on first day of multiple dosing of MK-3614 (Day 1) and last day of multiple dosing of MK-3614 (Day 10) to determine the Tmax in Panel A participants. Tmax was defined as time to the maximum concentration of MK-3614 reached over 12 hours.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel A: Time to Maximum Concentration (Tmax) of MK-3614
First Day (Day 1)
|
4.0 hr
Interval 4.0 to 6.0
|
—
|
—
|
—
|
—
|
|
Panel A: Time to Maximum Concentration (Tmax) of MK-3614
Last Day (Day 10)
|
4.0 hr
Interval 2.0 to 4.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Days 4, 13: Predose and 0.5, 1, 2, 3 ,4, 5, 6, 8 & 12 hours postdosePopulation: All participants in Panel D who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the Tmax. No participants were enrolled in Panel E.
Blood samples were collected at predose and up to 12 hours on first day of multiple dosing of MK-3614 (Day 4) and last day of multiple dosing of MK-3614 (Day 13) to determine the Tmax in Panel D participants. Tmax was defined as time to the maximum concentration of MK-3614 reached over 12 hours among participants in Panel D.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel D: Time to Maximum Concentration (Tmax) of MK-3614
First Day (Day 4)
|
—
|
—
|
—
|
4.5 hr
Interval 4.0 to 5.0
|
—
|
|
Panel D: Time to Maximum Concentration (Tmax) of MK-3614
Last Day (Day 13)
|
—
|
—
|
—
|
4.5 hr
Interval 3.0 to 5.0
|
—
|
PRIMARY outcome
Timeframe: Days 1, 10: Predose and 1, 2, 4, 6, 8, 12, 16, & 24 hours postdosePopulation: All participants in Panels B \& C who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the Tmax were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at predose and up to 24 hours on first day of multiple dosing of MK-3614 (Day 1) and last day of multiple dosing of MK-3614 (Day 10) to determine the Tmax in Panel B \& C participants. Tmax was defined as time to the maximum concentration of MK-3614 reached over 24 hours.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panels B, C: Time to Maximum Concentration (Tmax) of MK-3614
First Day (Day 1)
|
—
|
4.0 hr
Interval 4.0 to 24.0
|
11.0 hr
Interval 4.0 to 24.0
|
—
|
—
|
|
Panels B, C: Time to Maximum Concentration (Tmax) of MK-3614
Last Day (Day 10)
|
—
|
6.0 hr
Interval 4.0 to 6.0
|
4.0 hr
Interval 4.0 to 6.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 10: Predose and 1, 2, 4, 6, 8, 12, 16, 24, 36, & 48 hours postdosePopulation: All participants in Panels A, B, \& C who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the t1/2 were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at pre-specified time points on Day 10 to determine t½ in Panels A, B, \& C participants who received multiple doses of MK-3614. Apparent t½ was defined as the time required to eliminate half the amount of MK-3614 from plasma concentration.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panels A, B & C: Apparent Terminal Half-Life (t1/2) of MK-3614
|
10.1 hr
Standard Deviation 0.7
|
12.7 hr
Standard Deviation 1.2
|
11.9 hr
Standard Deviation 2.7
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 13: Predose and 0.5 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, & 48 hours postdosePopulation: All participants in Panel D who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the t1/2 were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at pre-specified time points on Day 13 to determine t½ in Panel D participants who received multiple doses of MK-3614. Apparent t½ was defined as the time required to eliminate half the amount of MK-3614 from plasma concentration.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel D: Apparent Terminal Half-Life (t1/2) of MK-3614
|
—
|
—
|
—
|
8.1 hr
Standard Deviation 1.3
|
—
|
PRIMARY outcome
Timeframe: Panels A, B & C: Day 10: Baseline & 24 hours postdose; Panel D: Day 13: Baseline & 24 hours postdose; Placebo: Day 10 or Day 13: Baseline & 24 hours postdosePopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had a baseline and at least one post baseline AIx value available on last day (Day 10 for Panels A, B, C and Day 13 on Panel D) were evaluated. No participants were enrolled in Panel E.
Aortic AIx is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. Aortic AIx was measured at pre-specified timepoints by aplanation tonometry of radial artery. Linear model containing panel as a fixed effect was used to report the change from baseline in aortic Aix at 24 hours postdose. The 90% confidence intervals (CIs) for the true mean difference (MK-3614-placebo) in change from baseline were obtained using the mean square error from the linear model. Placebo data was pooled across all panels for the analysis. A decrease in the point estimate of ≥ 5 percentage points was considered clinically meaningful.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=7 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Change From Baseline in Aortic Augmentation Index (AIx) at 24 Hours Postdose After Multiple Doses of MK-3614 or Placebo
|
-9.94 Percentage of central pulse pressure
Interval -14.32 to -5.57
|
-1.0 Percentage of central pulse pressure
Interval -6.36 to 4.36
|
-9.25 Percentage of central pulse pressure
Interval -13.04 to -5.46
|
-2.25 Percentage of central pulse pressure
Interval -6.04 to 1.54
|
-5.78 Percentage of central pulse pressure
Interval -8.87 to -2.68
|
PRIMARY outcome
Timeframe: Panels A, B, C: Days 1, 10: Predose & 1, 2, 3, 4, 5, 6, 8, 10, 12 hours postdose; Panel D: Days 1, 4, 13: Predose & 1, 2, 3, 4, 5, 6, 8, 10, 12 hours postdose; Placebo: Days 1 & 10 or 1, 4, 13: Predose & 1, 2, 3, 4, 5, 6, 8, 10, 12 hours postdosePopulation: All participants who received MK-3614 dose or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the HR were evaluated. Due to differing dosing schedules, some time points were not applicable for certain arms (indicated by zero participants analyzed entered in the table). No participants were enrolled in Panel E.
HR was measured with a validated automatic device. TWA 0-12hrs equals all HR values over 12-hr observation period multiplied by length of time participant spent at each HR value by that HR value; added products together,\& divided by observation period duration. Linear mixed effects model with panel, day, panel by day interaction as fixed effects \& participant-within-panel as random effect was used to generate TWA 0-12hrs on 1st day of single dosing (Panel D: Day 1) or 1st day of multiple dosing of MK-3614/placebo (Panels A,B,C: Day 1; Panel D: Day 4) and last day of multiple dosing of MK-3614/placebo (Panels A,B,C: Day 10; Panel D: Day 13) \& 90% CIs for true TWA using appropriate components of variance. Pooled placebo data at Day 1 indicates first day of single dosing (Panel D: Day 1) \& first day of multiple dosing of placebo (Panels A,B,C: Day 1; Panel D: Day 4) \& at Day 10 indicates last day of multiple dosing of placebo from all panels (Panels A,B,C: Day 10; Panel D: Day 13).
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=8 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Time-weighted Average Across 12 Hours (TWA 0-12hrs) for Heart Rate (HR) After Administration of MK-3614 or Placebo
Day 1
|
62.15 beats per minute (bpm)
Interval 60.92 to 63.37
|
63.58 beats per minute (bpm)
Interval 62.36 to 64.8
|
63.04 beats per minute (bpm)
Interval 61.82 to 64.27
|
69.84 beats per minute (bpm)
Interval 68.26 to 71.42
|
66.80 beats per minute (bpm)
Interval 65.84 to 67.76
|
|
Time-weighted Average Across 12 Hours (TWA 0-12hrs) for Heart Rate (HR) After Administration of MK-3614 or Placebo
Day 4
|
—
|
—
|
—
|
70.18 beats per minute (bpm)
Interval 66.68 to 71.67
|
—
|
|
Time-weighted Average Across 12 Hours (TWA 0-12hrs) for Heart Rate (HR) After Administration of MK-3614 or Placebo
Day 10
|
61.12 beats per minute (bpm)
Interval 59.9 to 62.34
|
63.00 beats per minute (bpm)
Interval 61.28 to 64.73
|
65.61 beats per minute (bpm)
Interval 64.39 to 66.83
|
—
|
66.76 beats per minute (bpm)
Interval 65.63 to 67.89
|
|
Time-weighted Average Across 12 Hours (TWA 0-12hrs) for Heart Rate (HR) After Administration of MK-3614 or Placebo
Day 13
|
—
|
—
|
—
|
69.82 beats per minute (bpm)
Interval 68.32 to 71.32
|
—
|
SECONDARY outcome
Timeframe: Panels A, B, C: Day 1: Baseline (0 hours) & up to 12 hours postdose; Panel D: Day 4: Baseline (0 hours) & up to 12 hours postdose; Placebo: Day 1 or Day 4: Baseline (0 hours) & up to 12 hours postdosePopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the SBP were evaluated. No participants were enrolled in Panel E.
Peripheral SBP was measured by the SphygmoCor® device. TWA 0-12hrs was obtained as follows: For all peripheral SBP values obtained over the 12-hour observation period (1, 2, 3, 4, 5, 6, 8, 10, 12 hours postdose), multiplied the length of time that the participant spent at each peripheral SBP value by that peripheral SBP value, added these products together, and then divided by duration of the observation period. Multiple dose effects of MK-3614 or placebo on peripheral SBP were estimated as a TWA change from baseline (0 hours) over the 12 hour postdose on first day of multiple dosing (Panels A, B, C: Day 1; Panel D: Day 4) and summarized descriptively. Placebo data was pooled across all panels for the analysis. Linear model containing panel as a fixed effect was used report the mean difference from placebo and associated 90% CIs after multiple doses of MK-3614 or placebo.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=8 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Systolic Blood Pressure (SBP) on First Day of Multiple Dosing of MK-3614 or Placebo
|
-9.47 mm Hg
Interval -26.08 to 3.69
|
-15.19 mm Hg
Interval -26.61 to -7.83
|
-14.36 mm Hg
Interval -31.53 to -6.29
|
-5.57 mm Hg
Interval -8.88 to 1.06
|
-5.88 mm Hg
Interval -26.6 to 7.01
|
SECONDARY outcome
Timeframe: Panels A, B, C: Day 1: Baseline (0 hours) & up to 12 hours; Panel D: Day 4: Baseline (0 hours) & up to 12 hours; Placebo: Day 1 or Day 4: Baseline (0 hours) & up to 12 hoursPopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the SBP were evaluated. No participants were enrolled in Panel E.
Peripheral SBP was measured by the SphygmoCor® device. TWA 0-12hrs was obtained as follows: For all peripheral SBP values obtained over the 12-hour observation period (1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose), multiplied the length of time that the participant spent at each peripheral SBP value by that peripheral SBP value, added these products together, and then divided by duration of the observation period. Multiple dose effects of MK-3614 or placebo on peripheral SBP were estimated as a TWA change from baseline (0 hours) over the 12 hour postdose on last day of multiple dosing (Panels A, B, C: Day 10; Panel D: Day 13) and summarized descriptively. Placebo data was pooled across all panels for the analysis. Linear model containing panel as a fixed effect was used report the mean difference from placebo and associated 90% CIs after multiple doses of MK-3614 or placebo.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=7 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Systolic Blood Pressure (SBP) on Last Day After Multiple Dosing of MK-3614 or Placebo
|
-10.25 mm Hg
Interval -32.22 to 3.89
|
-19.33 mm Hg
Interval -28.5 to -11.82
|
-15.61 mm Hg
Interval -38.92 to -0.01
|
-14.05 mm Hg
Interval -19.54 to -6.81
|
-8.29 mm Hg
Interval -20.51 to 0.85
|
SECONDARY outcome
Timeframe: Panels A, B, C: Day 10: Baseline (0 hours) & up to 24 hours postdose; Panel D: Day 13: Baseline (0 hours) & up to 24 hours postdose; Placebo: Day 10 or Day 13: Baseline (0 hours) & up to 24 hours postdosePopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the SBP were evaluated. No participants were enrolled in Panel E.
Peripheral SBP was measured by the SphygmoCor® device. TWA 0-24hrs was obtained as follows: For all peripheral SBP values obtained over the 24-hour observation period (1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 24 hours postdose), multiplied the length of time that the participant spent at each peripheral SBP value by that peripheral SBP value, added these products together, and then divided by duration of the observation period. Multiple dose effects of MK-3614 or placebo on peripheral SBP were estimated as a TWA change from baseline (0 hours) over the 24 hour postdose on last day of multiple dosing (Panels A, B \& C - Day 10; Panel D - Day 13) and summarized descriptively. Placebo data was pooled across all panels for the analysis. Linear model containing panel as a fixed effect was used report the mean difference from placebo and associated 90% CIs after multiple doses of MK-3614 or placebo.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=7 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Change From Baseline in Time-Weighted Average Across 24 Hours (TWA 0-24hrs) of Peripheral Systolic Blood Pressure (SBP) on Last Day of Multiple Dosing of MK-3614 or Placebo
|
-11.37 mm Hg
Interval -34.75 to 6.58
|
-18.59 mm Hg
Interval -27.29 to -11.51
|
-17.66 mm Hg
Interval -42.57 to -5.52
|
-15.43 mm Hg
Interval -18.42 to -7.11
|
-9.15 mm Hg
Interval -20.3 to -2.03
|
SECONDARY outcome
Timeframe: Panels A, B, C: Day 1: Baseline (0 hours) & up to 12 hours postdose; Panel D: Day 4: Baseline (0 hours) & up to 12 hours postdose; Placebo: Day 1 or Day 4: Baseline (0 hours) & up to 12 hours postdosePopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the DBP were evaluated. No participants were enrolled in Panel E.
Peripheral DBP was measured by the SphygmoCor® device. TWA 0-12hrs was obtained as follows: For all peripheral DBP values obtained over the 12-hour observation period (1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose), multiplied the length of time that the participant spent at each peripheral DBP value by that peripheral DBP value, added these products together, and then divided by duration of the observation period. Multiple dose effects of MK-3614 or placebo on peripheral DBP were estimated as a TWA change from baseline (0 hours) over the 12 hour postdose on first day of multiple dosing (Panels A, B, C: Day 1; Panel D: Day 4) and summarized descriptively. Placebo data was pooled across all panels for the analysis. Linear model containing panel as a fixed effect was used report the mean difference from placebo and associated 90% CIs after multiple doses of MK-3614 or placebo.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=8 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Diastolic Blood Pressure (DBP) on First Day of Multiple Dosing of MK-3614 or Placebo
|
-8.32 mm Hg
Interval -16.63 to -1.82
|
-13.18 mm Hg
Interval -21.01 to -5.75
|
-9.85 mm Hg
Interval -18.72 to -2.92
|
-3.97 mm Hg
Interval -9.51 to 0.85
|
-3.17 mm Hg
Interval -9.64 to 4.51
|
SECONDARY outcome
Timeframe: Panels A, B, C: Day 10: Baseline (0 hours) & up to 12 hours postdose; Panel D: Day 13: Baseline (0 hours) & up to 12 hours postdose; Placebo: Day 10 or Day 13: Baseline (0 hours) & up to 12 hours postdosePopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the DBP were evaluated. No participants were enrolled in Panel E.
Peripheral DBP was measured by the SphygmoCor® device. TWA 0-12hrs was obtained as follows: For all peripheral DBP values obtained over the 12-hour observation period (1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose), multiplied the length of time that the participant spent at each peripheral DBP value by that peripheral DBP value, added these products together, and then divided by duration of the observation period. Multiple dose effects of MK-3614 or placebo on peripheral DBP were estimated as a TWA change from baseline (0 hours) over the 12 hour postdose on last day of multiple dosing (Panels A, B, C: Day 10; Panel D: Day 13) and summarized descriptively. Placebo data was pooled across all panels for the analysis. Linear model containing panel as a fixed effect was used report the mean difference from placebo and associated 90% CIs after multiple doses of MK-3614 or placebo.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=7 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Change From Baseline in Time-Weighted Average Across 12 Hours (TWA 0-12hrs) of Peripheral Diastolic Blood Pressure (DBP) on Last Day of Multiple Dosing of MK-3614 or Placebo
|
-10.81 mm Hg
Interval -21.67 to -3.29
|
-15.43 mm Hg
Interval -24.79 to -10.5
|
-10.50 mm Hg
Interval -22.11 to -2.21
|
-8.58 mm Hg
Interval -14.51 to -3.78
|
-3.43 mm Hg
Interval -9.74 to 8.4
|
SECONDARY outcome
Timeframe: Panels A, B, C: Day 10: Baseline (0 hours) & up to 24 hours postdose; Panel D: Day 13: Baseline (0 hours) & up to 24 hours postdose; Placebo: Day 10 or Day 13: Baseline (0 hours) & up to 24 hours postdosePopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who received multiple doses of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the DBP were evaluated. No participants were enrolled in Panel E.
Peripheral DBP was measured by the SphygmoCor® device. TWA 0-24hrs was obtained as follows: For all peripheral DBP values obtained over the 24-hour observation period (1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 24 hours postdose), multiplied the length of time that the participant spent at each peripheral DBP value by that peripheral DBP value, added these products together, and then divided by duration of the observation period. Multiple dose effects of MK-3614 or placebo on peripheral DBP were estimated as a TWA change from baseline (0 hours) over the 12 hour postdose on last day of multiple dosing (Panels A, B, C: Day 10; Panel D: Day 13) and summarized descriptively. Placebo data was pooled across all panels for the analysis. Linear model containing panel as a fixed effect was used report the mean difference from placebo and associated 90% CIs after multiple doses of MK-3614 or placebo.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=7 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Change From Baseline in Time-Weighted Average Across 24 Hours (TWA 0-24hrs) of Peripheral Diastolic Blood Pressure (DBP) on Last Day of Multiple Dosing of MK-3614 or Placebo
|
-10.43 mm Hg
Interval -22.92 to -2.12
|
-15.64 mm Hg
Interval -23.27 to -11.54
|
-10.65 mm Hg
Interval -22.06 to -6.24
|
-9.89 mm Hg
Interval -14.24 to -5.03
|
-4.17 mm Hg
Interval -10.94 to 7.85
|
SECONDARY outcome
Timeframe: Panels B, C: Day 10: Baseline (0 hours) & 5 hours postdose; Panel D: Day 13: Baseline (0 hours) & 5 hours postdose; Placebo: Day 10 or Day 13: Baseline (0 hours) & 5 hours postdosePopulation: All participants in Panels B, C \& D who received multiple doses of MK-3614 or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the BT were evaluated. No participants were enrolled in Panel E.
Blood was drawn at baseline (0 hours) and 5 hours postdose on last day (Panels B, C: Day 10; Panel D: Day 13 per protocol) to assess bleeding time using a Newborn Surgicutt device. Linear model containing panel as a fixed effect was used to generate fold change from baseline and associated 90% CIs. Placebo data was pooled across panels B, C and D for the analysis.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=5 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panels B, C, & D: Change From Baseline in Bleeding Time (BT) at 5 Hours Postdose on Last Day After Multiple Doses of MK-3614 or Placebo
|
—
|
1.21 seconds
Interval 0.7 to 2.08
|
0.61 seconds
Interval 0.4 to 0.94
|
1.23 seconds
Interval 0.77 to 1.97
|
1.29 seconds
Interval 0.85 to 1.96
|
SECONDARY outcome
Timeframe: Panels A, B & C: Day 10: Predose & 4, 24 hours postdose; Panel D: Day 13: Predose & 4, 24 hours postdose; Placebo: Day 10 or Day 13: Predose & 4, 24 hours postdosePopulation: All participants who received multiple doses of MK-3614 or a matching placebo, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the cGMP. No participants were enrolled in Panel E.
Whole Blood was drawn at predose (baseline) and at 4, 24 hours postdose on last day of multiple dosing of MK-3614 (Panels A, B \& C: Day 10; Panel D: Day 13) to measure cGMP concentration levels. Linear mixed effects model containing panel, time, and panel by time interaction as fixed effects and participant within panel as a random effect was used to generate geometric mean and associated 90% CIs. Placebo data was pooled across all panels for the analysis.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 Participants
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=3 Participants
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 Participants
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=7 Participants
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Cyclic Guanosine Monophosphate (cGMP) Concentration Levels After Multiple Doses of MK-3614
24 Hours
|
456.28 pmole cGMP/g protein
Interval 336.84 to 618.07
|
627.72 pmole cGMP/g protein
Interval 408.71 to 964.2
|
567.14 pmole cGMP/g protein
Interval 418.68 to 768.16
|
497.20 pmole cGMP/g protein
Interval 342.85 to 721.04
|
262.41 pmole cGMP/g protein
Interval 198.13 to 347.51
|
|
Cyclic Guanosine Monophosphate (cGMP) Concentration Levels After Multiple Doses of MK-3614
Predose
|
443.55 pmole cGMP/g protein
Interval 327.44 to 600.82
|
507.86 pmole cGMP/g protein
Interval 330.63 to 780.0
|
517.34 pmole cGMP/g protein
Interval 381.95 to 700.78
|
405.57 pmole cGMP/g protein
Interval 279.7 to 588.16
|
269.72 pmole cGMP/g protein
Interval 203.65 to 357.2
|
|
Cyclic Guanosine Monophosphate (cGMP) Concentration Levels After Multiple Doses of MK-3614
4 Hours
|
515.43 pmole cGMP/g protein
Interval 380.51 to 698.13
|
532.62 pmole cGMP/g protein
Interval 346.78 to 818.11
|
721.33 pmole cGMP/g protein
Interval 532.51 to 977.01
|
394.89 pmole cGMP/g protein
Interval 272.3 to 572.66
|
316.43 pmole cGMP/g protein
Interval 233.62 to 428.63
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 14, & 24 hours postdosePopulation: All participants in Panel D who received single day dose of MK-3614, who complied with the protocol sufficiently to ensure that these data exhibited the effects of treatment, according to the underlying scientific model and had available data for the AUC 0-24 hours were evaluated. No participants were enrolled in Panel E.
Blood samples were collected at pre-specified timepoints to determine the AUC 0-24hrs of MK-3614 in Panel D participants who received single daily dosing on Day 1. AUC 0-24hrs was defined as the area under the concentration-time curve of MK-3614 from time zero to 24 hours. AUC 0-24hrs was reported instead of AUC 0-inf since Panel D participants received single daily dosing only on Day 1.
Outcome measures
| Measure |
MK-3614 0.25 mg (Panel A)
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 Participants
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Panel D: Area Under the Concentration Time-Curve From Hour 0 to 24 Hours (AUC 0-24hrs) of MK-3614
|
—
|
—
|
—
|
290.0 nM*hr
Standard Deviation 39.6
|
—
|
Adverse Events
MK-3614 0.25 mg (Panel A)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
MK-3614 0.50/0.25 mg (Panel B)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
MK-3614 0.50/0.25 mg (Panel C Repeat)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
MK-3614 0.50 mg (Panel D)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Placebo (All Panels)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
MK-3614 0.25 mg (Panel A)
n=6 participants at risk
Participants received 0.25 mg of MK-3614 twice daily (BID) every 12 hours orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel B)
n=6 participants at risk
Participants received 0.50 mg of MK-3614 in the morning (AM) and 0.25 mg of MK-3614 in the evening (PM), 12 hours apart orally for 10 days.
|
MK-3614 0.50/0.25 mg (Panel C Repeat)
n=6 participants at risk
Per protocol amendment, the Panel B dose was repeated, and participants received instead 0.50 mg of MK-3614 in the AM, and 0.25 mg of MK-3614 in the PM, 12 hours apart orally for 10 days.
|
MK-3614 0.50 mg (Panel D)
n=4 participants at risk
Participants received single day dose of 0.50 mg of MK-3614 three times a day (TID) every 8 hours on Day 1 followed by a wash out period for Days 2, 3 and multiple doses of 0.50 mg of MK-3614 BID every 12 hours orally for 10 days (Days 4-13).
|
Placebo (All Panels)
n=8 participants at risk
Participants received a dose matched placebo orally according to randomization.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Extrasystoles
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
12.5%
1/8 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Anal haemorrhage
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Faeces pale
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
12.5%
1/8 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
General disorders
Asthenia
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
General disorders
Chest pain
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
General disorders
Influenza like illness
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
12.5%
1/8 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
General disorders
Vessel puncture site haematoma
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 2 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Dizziness postural
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 3 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 2 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
12.5%
1/8 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 2 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Peripheral paralysis
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
33.3%
2/6 • Number of events 2 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Nervous system disorders
Visual field defect
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Psychiatric disorders
Anxiety disorder
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Psychiatric disorders
Nervousness
|
16.7%
1/6 • Number of events 2 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/4 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/6 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
25.0%
1/4 • Number of events 1 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
0.00%
0/8 • Non-serious AEs, serious AEs and all-cause mortality were collected for up to approximately 27 days.
All-Cause mortality is reported for all enrolled participants. Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in Panel E since the study objectives were achieved after enrolling 4 participants in Panel D.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
- Publication restrictions are in place
Restriction type: OTHER