MK-0616 (Oral PCSK9 Inhibitor) Renal Impairment Study 2 (MK-0616-020)
Study Details
Study Description
Brief Summary
The primary objective of the study is to compare the plasma pharmacokinetics (PK) of MK-0616 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Panel A: Moderate Renal Impairment (RI) Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days) |
Drug: MK-0616
Single oral dose
|
| Experimental: Panel B: Severe RI Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days) |
Drug: MK-0616
Single oral dose
|
| Experimental: Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD) Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days). Period 2 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 2 = 15 days). A washout period of 14 days will separate Period 1 and Period 2. |
Drug: MK-0616
Single oral dose
|
| Experimental: Panel D: Healthy Period 1 Day 1: Participants receive MK-0616 20 mg tablet single dose orally (Period 1 = 15 days) |
Drug: MK-0616
Single oral dose
|
Outcome Measures
Primary Outcome Measures
- Panels A, B, and D: Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-Inf) of MK-0616: Period 1 [Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (Period 1 = 15 days)]
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-0616
- Panel C: AUC0-inf of MK-0616: Periods 1 and 2 [Periods 1 and 2: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (each period = 15 days)]
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-0616
- Panels A, B and D: AUC from Time 0 to Last Measurable Concentration (AUClast) of MK-0616: Period 1 [Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (Period 1 = 15 days)]
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUClast of MK-0616
- Panel C: AUClast of MK-0616: Periods 1 and 2 [Periods 1 and 2: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose (each period = 15 days]
Blood for plasma samples will be collected at pre-specified timepoints to determine the AUClast of MK-0616
- Panels A, B and D: Maximum Plasma Concentration (Cmax) of MK-0616: Period 1 [Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 postdose (Period 1 = 15 days)]
Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of MK-0616
- Panel C: Maximum Plasma Concentration (Cmax) of MK-0616: Periods 1 and 2 [Periods 1 and 2: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose (each period = 15 days]
Blood for plasma samples will be collected at pre-specified time points to determine the Cmax of MK-0616
- Panel A, B, and D: Time to Maximum Plasma Concentration (Tmax) of MK-0616: Period 1 [Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose]
Blood for plasma samples will be collected at pre-specified time points to determine the Tmax of MK-0616
- Panel C: Time to Maximum Plasma Concentration (Tmax) of MK-0616: Periods 1 and 2 [Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose]
Blood for plasma samples will be collected at pre-specified time points to determine the Tmax of MK-0616
- Panels A, B and D: Apparent Terminal Half-life (t1/2) of MK-0616: Period 1 [Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose]
Blood for plasma samples will be collected at pre-specified time points to determine the t1/2 of MK-0616
- Panel C: t1/2 of MK-0616: Periods 1 and 2 [Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose]
Blood for plasma samples will be collected at pre-specified time points to determine the t1/2 of MK-0616
- Panel A, B and D: Apparent Clearance (CL/F) of MK-0616: Period 1 [Period 1: Predose and 0.5, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose (Period 1 = 15 days)]
Blood for plasma samples will be collected at pre-specified time points to determine the CL/F of MK-0616
- Panel C: Apparent Clearance (CL/F) of MK-0616: Periods 1 and 2 [Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose]
Blood for plasma samples will be collected at pre-specified time points to determine the CL/F of MK-0616
- Panels A, B and D: Apparent Volume of Distribution (Vz/F) of MK-0616 [Period 1: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose]
Blood for plasma samples will be collected at pre-specified time points to determine the Vz/F of MK-0616
- Panel C: Apparent Volume of Distribution (Vz/F) of MK-0616 [Periods 1 and 2: Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168 and 240 hours postdose]
Blood for plasma samples will be collected at pre-specified time points to determine the Vz/F of MK-0616
Secondary Outcome Measures
- Dialysate Clearance (CLd) of MK-0616 [Predose and up to 8 hours postdose- Panel C (Period 2)]
CLd is the amount of MK-0616 cleared from plasma via dialysis.
- Dialysate Concentration of MK-0616 [Predose and up to 8 hours postdose- Panel C (Period 2)]
Cd is the concentration of MK-0616 in dialysate.
- Amount of MK-0616 Excreted (AEd) in Dialysate [Predose and up to 8 hours postdose- Panel C (Period 2)]
The amount of MK-0616 excreted in the dialysate will be assessed.
- Percentage of Dose (%Dose) of MK-0616 Excreted in Dialysate [Predose and up to 8 hours postdose- Panel C (Period 2)]
The percentage of the dose of MK-0616 in the dialysate will be assessed.
- Amount of MK-0616 Excreted in Urine from 0 to 24 hours (AE0-24) [Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)]
The amount of MK-0616 excreted in urine in first 24 hours after dosing will be reported.
- Fraction of Unchanged MK-0616 Excreted in Urine (Fe) [Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)]
The fraction of unchanged MK-0616 excreted in urine will be reported
- Renal Clearance (CLr) of MK-0616 [Predose and up to 24 hours postdose (All Panels: Period 1; Panel C: Period 2)]
The CLr of MK-0616 will be reported
- Percentage of Participants Who Experience at Least 1 Adverse Event (AE) [Up to approximately 30 days]
An AE is 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
- Percentage of Participants Who Discontinue From the Study due to an AE [Up to approximately 30 days]
An AE is 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
Eligibility Criteria
Criteria
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 and the Sponsor.
-
Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 40 kg/m2, 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 renal transplant.
-
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 0616-020
- MK-0616-020