Hypercholesterolaemia
Conditions
Brief summary
The primary objective of the study is to compare the plasma pharmacokinetics (PK) of enlicitide decanoate following a single 20 mg dose in participants on a background of statin therapy with varying degrees of renal impairment (moderate, severe, end stage renal disease \[ESRD\]) to those of healthy mean matched control participants on a background of statin therapy. There is no formal hypothesis.
Detailed description
Panel C included participants with ESRD. No urine samples could be obtained on Panel C participants and hence no pharmacokinetic (PK) analysis could be performed for Panel C participants as pre-specified in the protocol.
Interventions
Oral dose
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Be in good health with the exception of renal impairment (RI) and hypercholesterolemia for participants in Panels A, B, and C. Participants with RI that have stable, chronic medical or psychiatric conditions, including but not limited to hypertension, hypercholesterolemia, diabetes mellitus, hyper- or hypothyroidism, gout, and chronic anxiety or depression may be included at the discretion of the investigator * Body Mass Index (BMI) ≥ 18 kg/m\^2 and ≤ 40 kg/m\^2, inclusive * Be on a stable dose of any statin therapy defined as: no changes to dose or type of statin therapy for at least 2 months prior to Screening and participant anticipates no changes to statin therapy throughout the study until the poststudy visit
Exclusion criteria
* History or presence of renal artery stenosis * Had a functioning renal transplant in the past 5 years and is taking transplant medication * Participants in panels A, B and D: Has rapidly fluctuating renal function as determined by historical measurements * Has a history gastrointestinal disease which might affect food and drug absorption, as determined by the investigator, or has had gastric bypass or similar surgery * History of cancer (malignancy) * History of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food * Has received an anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) small molecule treatment, monoclonal antibody, or short interfering RNA (siRNA) or RNA interference (ie, Inclisiran) within 12 months prior to Screening * Participants with RI (Panels A, B, and C): Taking medications to treat chronic medical conditions and/or conditions associated with renal disease, if participant has not been on a stable regimen for at least 1 month (other than statins, which require a stable dose for at least 2 months) prior to administration of the initial dose of study intervention, and/or is unable to withhold the use of the medication(s) within 4 hours prior to and 4 hours after administration of study intervention * Participated in another investigational study within 4 weeks prior to the prestudy (screening) visit * Consumes greater than 3 servings of alcoholic beverages per day * Consumes excessive amounts, defined as greater than 6 servings of caffeinated beverages per day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate | Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose | AUC0-inf was a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood for plasma samples was collected at pre-specified timepoints to determine the AUC0-inf of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUC0-inf. Per protocol, mean AUC0-inf was reported. |
| AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate | Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose | AUClast was defined as the area under the concentration-time curve of enlicitide decanoate from time zero to last measurable concentration. Blood for plasma samples was collected at pre-specified timepoints to determine the AUClast of enlicitide decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUClast. Per protocol, mean AUClast was reported. |
| Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate | Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose | Cmax was defined as the maximum or peak concentration of enlicitide decanoate observed after its administration. Blood for plasma samples was collected at pre-specified time points to determine the Cmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Cmax. Per protocol, mean Cmax was reported. |
| Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate | Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose | Tmax was defined as the time required for a study drug to reach maximum concentration in plasma. Blood for plasma samples was collected at pre-specified time points to determine the Tmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Tmax. Per protocol, mean Tmax was reported. |
| Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate | Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose | Half-life (t1/2) was defined as the time required for plasma drug concentration of enclitide decanoate to decrease by 50% from peak. Blood for plasma samples was collected at pre-specified time points to determine the t1/2 of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report t1/2. Per protocol, mean t1/2 was reported. |
| Apparent Clearance (CL/F) of Enlicitide Decanoate | Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose | CL/F was the apparent total clearance of enlicitide decanoate in plasma over time. Blood for plasma samples was collected at pre-specified timepoints to determine the CL/F of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report CL/F. Per protocol, mean CL/F was reported. |
| Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate | Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose | Vz/F was the apparent volume of distribution of enlicitide decanoate between the plasma and the rest of the body, after dose, assessed as the total volume of enlicitide decanoate that would need to be uniformly distributed to achieve the desired plasma drug concentration. Blood for plasma samples was collected at pre-specified time points to determine the Vz/F of Enlicitide Decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Vz/F. Per protocol, mean Vz/F was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 30 days | 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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported. |
| Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate | Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose | CLd was the measure of the amount of enlicitide decanoate cleared from plasma via dialysis. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean CLd. |
| Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE | Up to approximately 30 days | 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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of Panel C participants who discontinued study treatment due to an AE were reported. |
| Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE | Up to approximately 30 days | 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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of Panel A, B, and D participants who discontinued study treatment due to an AE were reported. |
| Panel C: Dialysate Concentration (Cd) of Enlicitide Decanoate | Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose | Cd was the measure of the concentration of enlicitide decanoate in dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean Cd. |
| Panel C: Amount of Enlicitide Decanoate Excreted (AEd) in Dialysate | Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose | AEd was the measure of the amount of enlicitide decanoate excreted in the dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean AEd. |
| Panel C: Percentage of Dose (%Dose) of Enlicitide Decanoate Excreted in Dialysate | Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose | %Dose was the percentage of the dose of enlicitide decanoate excreted in the dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine %Dose. |
| Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate | Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose | AE0-24 was the measure of the amount of enlicitide decanoate excreted at 0 to 24 hours. Urine samples were to be collected to determine the AE0-24 after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report AE0-24. Per protocol, mean AE0-24 was reported. |
| Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe) | Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose | Fe was the measure of the percentage of unchanged enlicitide decanoate excreted in the urine. The percentage of enlicitide decanoate that was excreted unchanged in urine over the 24-hr collection interval (Fe) was calculated as 100 times the ratio of Ae0-24 and dose. Urine samples were to be collected to determine the Fe after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Fe. |
| Renal Clearance (CLr) of Enlicitide Decanoate | Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose | CLr was the measure of how quickly enlicitide decanoate was removed from the plasma by the kidney and excreted in urine. Urine samples were to be collected to determine the CLr after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report CLr. Per protocol, mean CLr was reported. |
Countries
United States
Participant flow
Pre-assignment details
All allocated participants. Panel C included participants with End-Stage Renal Disease (ESRD). No urine samples could be obtained on Panel C participants and hence no pharmacokinetic (PK) analysis could be performed for Panel C participants as pre-specified in the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Panel A: Moderate Renal Impairment (RI) Participants received Enlicitide Decanoate 20 mg tablet single dose orally on Day 1. | 8 |
| Panel B: Severe RI Participants received Enlicitide Decanoate 20 mg tablet single dose orally on Day 1. | 8 |
| Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD) Participants received Enlicitide Decanoate 20 mg tablet orally on Day 1 and Day 16. | 9 |
| Panel D: Healthy Controls Participants received Enlicitide Decanoate 20 mg tablet single dose orally on Day 1. | 8 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Panel A: Moderate Renal Impairment (RI) | Panel B: Severe RI | Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD) | Panel D: Healthy Controls | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67 Years STANDARD_DEVIATION 9.6 | 66.8 Years STANDARD_DEVIATION 12.1 | 60.1 Years STANDARD_DEVIATION 9.6 | 62.8 Years STANDARD_DEVIATION 4 | 64 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 2 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 6 Participants | 7 Participants | 3 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 7 Participants | 3 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 3 Participants | 2 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 1 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 8 Participants | 6 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 2 / 8 | 2 / 8 | 0 / 9 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 1 / 9 | 0 / 8 |
Outcome results
Primary
Apparent Clearance (CL/F) of Enlicitide Decanoate
CL/F was the apparent total clearance of enlicitide decanoate in plasma over time. Blood for plasma samples was collected at pre-specified timepoints to determine the CL/F of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report CL/F. Per protocol, mean CL/F was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Population: All participants of Panel A, B, C, and D who received at least a dose of study treatment and had data available for the CL/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Apparent Clearance (CL/F) of Enlicitide Decanoate | 17.6 Liter/hr |
| Panel B: Severe RI | Apparent Clearance (CL/F) of Enlicitide Decanoate | 23.3 Liter/hr |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Apparent Clearance (CL/F) of Enlicitide Decanoate | 15.2 Liter/hr |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | Apparent Clearance (CL/F) of Enlicitide Decanoate | 22.6 Liter/hr |
| Panel D: Healthy Controls | Apparent Clearance (CL/F) of Enlicitide Decanoate | 26.5 Liter/hr |
90% CI: [0.43, 1.02]
90% CI: [0.58, 1.35]
90% CI: [0.36, 0.91]
90% CI: [0.57, 1.29]
Primary
Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate
Half-life (t1/2) was defined as the time required for plasma drug concentration of enclitide decanoate to decrease by 50% from peak. Blood for plasma samples was collected at pre-specified time points to determine the t1/2 of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report t1/2. Per protocol, mean t1/2 was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Population: All participants of Panel A, B, C, and D who received at least a dose of study treatment and had data available for the t1/2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate | 81.5 hours | Geometric Coefficient of Variation 70.4 |
| Panel B: Severe RI | Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate | 56.4 hours | Geometric Coefficient of Variation 32.7 |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate | 53.6 hours | Geometric Coefficient of Variation 36.9 |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate | 75.6 hours | Geometric Coefficient of Variation 62.9 |
| Panel D: Healthy Controls | Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate | 46 hours | Geometric Coefficient of Variation 60.8 |
Primary
Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate
Vz/F was the apparent volume of distribution of enlicitide decanoate between the plasma and the rest of the body, after dose, assessed as the total volume of enlicitide decanoate that would need to be uniformly distributed to achieve the desired plasma drug concentration. Blood for plasma samples was collected at pre-specified time points to determine the Vz/F of Enlicitide Decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Vz/F. Per protocol, mean Vz/F was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Population: All participants of Panel A, B, C, and D who received at least a dose of study treatment and had data available for the Vz/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate | 2070 Liter |
| Panel B: Severe RI | Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate | 1890 Liter |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate | 1170 Liter |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate | 2470 Liter |
| Panel D: Healthy Controls | Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate | 1760 Liter |
90% CI: [0.78, 1.5]
90% CI: [0.5, 0.89]
90% CI: [1, 1.97]
90% CI: [0.83, 1.67]
Primary
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate
AUC0-inf was a measure of the total amount of drug in the plasma from the dose administration extrapolated to infinity. Blood for plasma samples was collected at pre-specified timepoints to determine the AUC0-inf of enlicitide decanoate for Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUC0-inf. Per protocol, mean AUC0-inf was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Population: All allocated participants of Panel A, B, C, and D who received at least a dose of study treatment and had data available for AUC0-inf.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate | 733 hr*nmol/Liter |
| Panel B: Severe RI | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate | 554 hr*nmol/Liter |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate | 850 hr*nmol/Liter |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate | 570 hr*nmol/Liter |
| Panel D: Healthy Controls | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate | 487 hr*nmol/Liter |
90% CI: [0.98, 2.31]
90% CI: [0.74, 1.74]Geometric Mean Ratio
90% CI: [1.1, 2.78]
90% CI: [0.77, 1.77]
Primary
AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate
AUClast was defined as the area under the concentration-time curve of enlicitide decanoate from time zero to last measurable concentration. Blood for plasma samples was collected at pre-specified timepoints to determine the AUClast of enlicitide decanoate in Panel A, B, C, and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C ESRD - enlicitide decanoate pre-hemodialysis and Panel C ESRD - enlicitide decanoate post-hemodialysis to report AUClast. Per protocol, mean AUClast was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Population: All participants of Panel A, B, C, and D who received at least a dose of study treatment and had data available for AUClast.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate | 735 hr*nmol/Liter |
| Panel B: Severe RI | AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate | 362 hr*nmol/Liter |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate | 649 hr*nmol/Liter |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate | 538 hr*nmol/Liter |
| Panel D: Healthy Controls | AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate | 456 hr*nmol/Liter |
90% CI: [1.05, 2.46]
90% CI: [0.37, 1.72]
90% CI: [0.8, 2.54]
90% CI: [0.78, 1.78]
Primary
Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate
Cmax was defined as the maximum or peak concentration of enlicitide decanoate observed after its administration. Blood for plasma samples was collected at pre-specified time points to determine the Cmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Cmax. Per protocol, mean Cmax was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Population: All participants of Panel A, B, C, and D who received at least a dose of study treatment and had data available for Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate | 9.56 nmol/Liter |
| Panel B: Severe RI | Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate | 5.8 nmol/Liter |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate | 8.73 nmol/Liter |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate | 9.08 nmol/Liter |
| Panel D: Healthy Controls | Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate | 9.72 nmol/Liter |
90% CI: [0.71, 1.37]
90% CI: [0.34, 1.04]
90% CI: [0.64, 1.27]
90% CI: [0.78, 1.78]
Primary
Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate
Tmax was defined as the time required for a study drug to reach maximum concentration in plasma. Blood for plasma samples was collected at pre-specified time points to determine the Tmax of enlicitide decanoate in Panel A, B, C and D participants. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Tmax. Per protocol, mean Tmax was reported.
Time frame: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
Population: All participants of Panel A, B, C and D who received at least a dose of study treatment and had data available for Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate | 16 hours |
| Panel B: Severe RI | Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate | 2.75 hours |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate | 18.01 hours |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate | 1.00 hours |
| Panel D: Healthy Controls | Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate | 1.0 hours |
Secondary
Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate
AE0-24 was the measure of the amount of enlicitide decanoate excreted at 0 to 24 hours. Urine samples were to be collected to determine the AE0-24 after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report AE0-24. Per protocol, mean AE0-24 was reported.
Time frame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose
Population: All participants from Panel A, B, C, and D who received a dose of study treatment and had data available for AE0-24 were to be analyzed. No urine samples were collected on Panel C participants; therefore, no data were reported for this group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate | 0.0213 mg |
| Panel B: Severe RI | Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate | 0.00592 mg |
| Panel D: Healthy Controls | Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate | 0.0662 mg |
90% CI: [0.14, 0.74]
90% CI: [0.04, 0.22]
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported.
Time frame: Up to approximately 30 days
Population: All allocated participants who received a dose of study treatment. Per protocol, AEs were not collected separately for Panel C ESRD - Enlicitide Decanoate pre-hemodialysis and Panel C ESRD Enlicitide Decanoate post-hemodialysis arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Panel B: Severe RI | Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Number of Participants Who Experienced an Adverse Event (AE) | 1 Participants |
| Panel C: ESRD - Enlicitide Decanoate Post-Hemodialysis | Number of Participants Who Experienced an Adverse Event (AE) | 0 Participants |
Secondary
Panel C: Amount of Enlicitide Decanoate Excreted (AEd) in Dialysate
AEd was the measure of the amount of enlicitide decanoate excreted in the dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean AEd.
Time frame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Population: Per protocol all participants of Panel C who received at least a dose of study treatment and had data available were to be analyzed. However, no urine samples could be collected on Panel C participants, thus no data were reported.
Secondary
Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate
CLd was the measure of the amount of enlicitide decanoate cleared from plasma via dialysis. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean CLd.
Time frame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Population: Per protocol all participants of Panel C who received at least a dose of study treatment and had data available were to be analyzed. However, no urine samples could be collected on Panel C participants, thus no data were reported.
Secondary
Panel C: Dialysate Concentration (Cd) of Enlicitide Decanoate
Cd was the measure of the concentration of enlicitide decanoate in dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine mean Cd.
Time frame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Population: Per protocol all participants of Panel C who received at least a dose of study treatment and had data available were to be analyzed. However, no urine samples could be collected on Panel C participants, thus no data were reported.
Secondary
Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE
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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of Panel C participants who discontinued study treatment due to an AE were reported.
Time frame: Up to approximately 30 days
Population: All allocated participants in Panels C who received a dose of study treatment. Per protocol, AEs were not collected separately for Panel C ESRD - Enlicitide Decanoate pre-hemodialysis and Panel C ESRD Enlicitide Decanoate post-hemodialysis arms.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE | 0 Participants |
Secondary
Panel C: Percentage of Dose (%Dose) of Enlicitide Decanoate Excreted in Dialysate
%Dose was the percentage of the dose of enlicitide decanoate excreted in the dialysate. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis. Urine samples were to be collected for Panel C participants to determine %Dose.
Time frame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Population: Per protocol all participants of Panel C who received at least a dose of study treatment and had data available were to be analyzed. However, no urine samples could be collected on Panel C participants, thus no data were reported.
Secondary
Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE
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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of Panel A, B, and D participants who discontinued study treatment due to an AE were reported.
Time frame: Up to approximately 30 days
Population: All allocated participants in Panels A, B and D who received a dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE | 0 Participants |
| Panel B: Severe RI | Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE | 0 Participants |
| Panel C: ESRD - Enlicitide Decanoate Pre-Hemodialysis | Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE | 0 Participants |
Secondary
Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe)
Fe was the measure of the percentage of unchanged enlicitide decanoate excreted in the urine. The percentage of enlicitide decanoate that was excreted unchanged in urine over the 24-hr collection interval (Fe) was calculated as 100 times the ratio of Ae0-24 and dose. Urine samples were to be collected to determine the Fe after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report Fe.
Time frame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Population: All participants from Panel A, B, C, and D who received a dose of study treatment and had data available for Fe were to be analyzed. No urine samples were collected on Panel C participants; therefore, no data were reported for this group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe) | 0.107 Percentage of Enlicitide Decanoate |
| Panel B: Severe RI | Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe) | 0.0296 Percentage of Enlicitide Decanoate |
| Panel D: Healthy Controls | Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe) | 0.331 Percentage of Enlicitide Decanoate |
90% CI: [0.14, 0.74]
90% CI: [0.04, 0.22]
Secondary
Renal Clearance (CLr) of Enlicitide Decanoate
CLr was the measure of how quickly enlicitide decanoate was removed from the plasma by the kidney and excreted in urine. Urine samples were to be collected to determine the CLr after administration of enlicitide decanoate for Panels A, B, C, and D. Per protocol, Panel C ESRD on HD arm was separated into two arms: Panel C enlicitide decanoate pre-hemodialysis and Panel C enlicitide decanoate post-hemodialysis to report CLr. Per protocol, mean CLr was reported.
Time frame: Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
Population: All participants from Panel A, B, C, and D who received a dose of study treatment and had data available for CLr were to be analyzed. No urine samples were collected on Panel C participants; therefore, no data were reported for this group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Panel A: Moderate Renal Impairment (RI) | Renal Clearance (CLr) of Enlicitide Decanoate | 0.0716 Liter/hr |
| Panel B: Severe RI | Renal Clearance (CLr) of Enlicitide Decanoate | 0.0347 Liter/hr |
| Panel D: Healthy Controls | Renal Clearance (CLr) of Enlicitide Decanoate | 0.243 Liter/hr |
90% CI: [0.16, 0.55]
90% CI: [0.06, 0.36]