Trial Outcomes & Findings for A Study of Enlicitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Participants With Moderate Renal Impairment (MK-0616-007) (NCT NCT05070390)
NCT ID: NCT05070390
Last Updated: 2024-09-26
Results Overview
Blood samples were collected at pre-specified timepoints to determine the AUC0-inf of MK-0616. AUC0-inf was defined as the area under the concentration-time curve of MK-0616 from time zero to infinity.
COMPLETED
PHASE1
18 participants
Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdose
2024-09-26
Participant Flow
Of 24 participants screened for inclusion, 18 participants were allocated to receive MK-0616 single dose 10-mg. All participants received at least one dose of study intervention.
Participant milestones
| Measure |
Panel A - Moderate Renal Impairment (RI)
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
8
|
|
Overall Study
COMPLETED
|
10
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Enlicitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Participants With Moderate Renal Impairment (MK-0616-007)
Baseline characteristics by cohort
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=10 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=8 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.5 Years
STANDARD_DEVIATION 5.6 • n=5 Participants
|
60.4 Years
STANDARD_DEVIATION 5.0 • n=7 Participants
|
63.8 Years
STANDARD_DEVIATION 6.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for AUC0-inf.
Blood samples were collected at pre-specified timepoints to determine the AUC0-inf of MK-0616. AUC0-inf was defined as the area under the concentration-time curve of MK-0616 from time zero to infinity.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=7 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=6 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of MK-0616
|
453 hour*nmol/Liter
Interval 211.0 to 972.0
|
369 hour*nmol/Liter
Interval 211.0 to 646.0
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for AUC0-last.
Blood samples were collected at pre-specified timepoints to determine the AUC0-last of MK-0616. AUC0-last was defined as the area under the concentration-time curve of MK-0616 from time zero to last measurable concentration.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=8 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=8 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Area Under the Concentration- Time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of MK-0616.
|
312 hour*nmol/Liter
Interval 120.0 to 815.0
|
192 hour*nmol/Liter
Interval 64.1 to 574.0
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for Cmax.
Blood samples were collected at pre-specified time points to determine the Cmax of MK-0616. Cmax was defined as the maximum concentration of MK-0616 reached.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=8 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=8 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of MK-0616
|
5.80 nmol/Liter
Interval 2.98 to 11.3
|
4.00 nmol/Liter
Interval 1.97 to 8.13
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for Tmax.
Blood samples were collected at pre-specified timepoints to determine the Tmax of MK-0616. Tmax was defined as time to the maximum concentration of MK-0616 reached.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=8 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=8 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of MK-0616
|
2.00 Hour
Interval 1.0 to 24.0
|
4.66 Hour
Interval 1.5 to 24.02
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for t1/2.
Blood samples were collected at pre-specified timepoints to determine the t1/2 of MK-0616. t1/2 was defined as the time required to divide the MK-0616 plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-0616.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=7 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=6 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Apparent Terminal Half-life (t1/2) of MK-0616
|
55.1 Hour
Geometric Coefficient of Variation 44.1
|
48.8 Hour
Geometric Coefficient of Variation 32.0
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for CL/F.
Blood samples were collected at pre-specified timepoints to determine the CL/F of MK-0616. CL/F was the apparent total clearance of MK-0616 in plasma over time, assessed as the rate at which MK-0616 was removed from the plasma.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=7 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=6 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Apparent Clearance (CL/F) of MK-0616
|
14.2 Liter/hour
Interval 6.63 to 30.6
|
17.5 Liter/hour
Interval 9.99 to 30.5
|
PRIMARY outcome
Timeframe: Predose and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 72, 120, 168, 240, and 336 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for Vz/F.
Blood samples were collected at pre-specified timepoints to determine the Vz/F of MK-0616. Vz/F was the apparent volume of distribution of MK-0616 between the plasma and the rest of the body, after dose, assessed as the total volume of MK-0616 that would need to be uniformly distributed to achieve the desired plasma drug concentration.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=7 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=6 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) of MK-0616
|
1130 Liter
Interval 675.0 to 1900.0
|
1230 Liter
Interval 972.0 to 1550.0
|
SECONDARY outcome
Timeframe: Up to approximately 14 daysPopulation: All allocated participants who received a dose of intervention.
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who experienced an AE were reported.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=10 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=8 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Number of Participants Who Experienced an Adverse Event (AE)
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 14 daysPopulation: All allocated participants who received a dose of study intervention.
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Number of participants who discontinued from the study due to an AE were reported.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=10 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=8 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Number of Participants Who Discontinued From the Study Due to an AE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Predose and at 0, 4, 8, 12 and 24 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for Ae0-24.
Urine samples were collected at pre-specified time points to determine the AE0-24 of MK-0616. Ae0-24 was defined as the amount of MK-0616 recovered in urine from time 0-24 hours.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=10 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=7 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Amount Recovered in Urine From 0 to 24 Hours (Ae0-24) of MK-0616
|
0.0116 Miligram
Interval 0.00288 to 0.0467
|
0.0141 Miligram
Interval 0.00485 to 0.0409
|
SECONDARY outcome
Timeframe: Predose and at 0, 4, 8, 12, 24, 36 and 48 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for Fe.
Urine samples were collected at pre-specified time points to determine the Fe of MK-0616. Fe was defined as the fraction of dose of MK-0616 recovered in urine.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=10 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=7 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Fraction of Dose Recovered in Urine (Fe) of MK-0616
|
0.116 Percent
Interval 0.0288 to 0.467
|
0.141 Percent
Interval 0.0485 to 0.409
|
SECONDARY outcome
Timeframe: Predose and 4, 8, 12, 24, 36, and 48 hours postdosePopulation: All allocated participants who received a dose of study intervention and had data available for CLr.
Urine samples were collected at pre-specified time points to determine the CLr of MK-0616. was defined as the time it takes for the MK-0616 to be completely removed by the kidneys.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=8 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=7 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Renal Clearance (CLr) of MK-0616
|
0.0573 Liter/hour
Interval 0.0157 to 0.209
|
0.152 Liter/hour
Interval 0.0781 to 0.294
|
SECONDARY outcome
Timeframe: Baseline (Predose) and up to 336 hours post dosePopulation: All allocated participants who received a dose of study intervention, and had a baseline measure and at least one postbaseline measure of PCSK9.
Urine samples were collected at pre-specified time points (baseline and 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48 and 336 hours postdose) to evaluate the reduction in free PCSK9 from baseline to up to 336 hours postdose after administration of MK-0616. The percent change from baseline in free PCSK9 was reported.
Outcome measures
| Measure |
Panel A - Moderate Renal Impairment (RI)
n=10 Participants
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
Panel B - Healthy Controls
n=8 Participants
Healthy matched control participants received a single dose of MK-0616 10 mg orally on Day 1.
|
|---|---|---|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 336 hours postdose
|
5.00 Percent Change
Interval -9.22 to 27.2
|
7.50 Percent Change
Interval -4.78 to 21.2
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 1 hour postdose
|
-80.5 Percent Change
Interval -83.6 to -36.3
|
-66.6 Percent Change
Interval -73.4 to -10.2
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 1.5 hours postdose
|
-90.9 Percent Change
Interval -97.7 to -66.2
|
-88.6 Percent Change
Interval -98.3 to -54.5
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 2 hours postdose
|
-90.8 Percent Change
Interval -96.5 to -68.9
|
-87.1 Percent Change
Interval -96.8 to -54.9
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 3 hours postdose
|
-89.7 Percent Change
Interval -96.1 to -67.1
|
-86.0 Percent Change
Interval -95.0 to -60.7
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 5 hours postdose
|
-89.6 Percent Change
Interval -94.8 to -73.5
|
-83.6 Percent Change
Interval -97.0 to -51.6
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 8 hours postdose
|
-84.9 Percent Change
Interval -91.6 to -64.3
|
-78.5 Percent Change
Interval -97.8 to -35.1
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 12 hours postdose
|
-71.8 Percent Change
Interval -80.4 to -43.5
|
-60.8 Percent Change
Interval -93.4 to 9.55
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 24 hours postdose
|
-67.2 Percent Change
Interval -75.2 to -43.8
|
-27.9 Percent Change
Interval -47.3 to 6.46
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 36 hours postdose
|
-54.9 Percent Change
Interval -64.6 to -30.9
|
1.38 Percent Change
Interval -26.4 to 47.2
|
|
Percent Change From Baseline in Free Proprotein Convertase Subtilisin Kexin 9 (PCSK9)
Change from baseline to 48 hours postdose
|
-44.9 Percent Change
Interval -56.6 to -15.3
|
5.11 Percent Change
Interval -10.2 to 26.2
|
Adverse Events
Panel A - Moderate RI
Panel A - Moderate Renal Impairment (RI)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Panel A - Moderate RI
n=10 participants at risk
Participants with moderate renal impairment (RI) received a single dose of MK-616 10mg orally on Day 1.
|
Panel A - Moderate Renal Impairment (RI)
n=8 participants at risk
Participants with moderate RI received a single dose of MK-616 10mg orally on Day 1.
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/10 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
12.5%
1/8 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/10 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
12.5%
1/8 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
|
General disorders
Axillary pain
|
10.0%
1/10 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
0.00%
0/8 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
|
General disorders
Fatigue
|
0.00%
0/10 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
12.5%
1/8 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.0%
1/10 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
0.00%
0/8 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.0%
1/10 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
0.00%
0/8 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
0.00%
0/8 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
|
Nervous system disorders
Headache
|
0.00%
0/10 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
12.5%
1/8 • Number of events 1 • Up to approximately 16 days
All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received a dose of study treatment.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding thist rial 45 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