MK-0616 (経口 PCSK9 阻害剤) 腎障害研究 2 (MK-0616-020)
さまざまな程度の腎障害を持つ参加者におけるMK-0616の薬物動態を評価するための非盲検単回投与臨床研究
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Florida
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Hallandale、Florida、アメリカ、33009
- Velocity Clinical Research, Hallandale Beach ( Site 0003)
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Miami、Florida、アメリカ、33014-3616
- Clinical Pharmacology of Miami ( Site 0005)
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Miami、Florida、アメリカ、33147
- Advanced Pharma CR, LLC ( Site 0001)
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Orlando、Florida、アメリカ、32809
- Orlando Clinical Research Center ( Site 0004)
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Tampa、Florida、アメリカ、33603
- Genesis Clinical Research, LLC ( Site 0002)
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Panel A: Moderate Renal Impairment (RI)
Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1 |
Oral dose
他の名前：
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実験的：Panel B: Severe RI
Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1 |
Oral dose
他の名前：
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実験的：Panel C: End-Stage Renal Disease (ESRD) on Hemodialysis (HD)
Participants receive Enlicitide Decanoate 20 mg tablet orally on Day 1 and Day 16. |
Oral dose
他の名前：
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実験的：Panel D: Healthy Controls
Participants receive Enlicitide Decanoate 20 mg tablet single dose orally on Day 1. |
Oral dose
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-Inf) of Enlicitide Decanoate
時間枠：Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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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. |
Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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AUC From Time 0 to Last Measurable Concentration (AUClast) of Enlicitide Decanoate
時間枠：Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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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. |
Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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Maximum Plasma Concentration (Cmax) of Enlicitide Decanoate
時間枠：Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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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. |
Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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Time to Maximum Plasma Concentration (Tmax) of Enlicitide Decanoate
時間枠：Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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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. |
Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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Apparent Terminal Half-life (t1/2) of Enlicitide Decanoate
時間枠：Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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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. |
Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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Apparent Clearance (CL/F) of Enlicitide Decanoate
時間枠：Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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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. |
Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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Apparent Volume of Distribution (Vz/F) of Enlicitide Decanoate
時間枠：Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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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. |
Predose and 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, 120, 168, and 240 hours postdose
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Panel C: Dialysate Clearance (CLd) of Enlicitide Decanoate
時間枠：Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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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. |
Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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Panel C: Dialysate Concentration (Cd) of Enlicitide Decanoate
時間枠：Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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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. |
Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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Panel C: Amount of Enlicitide Decanoate Excreted (AEd) in Dialysate
時間枠：Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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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. |
Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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Panel C: Percentage of Dose (%Dose) of Enlicitide Decanoate Excreted in Dialysate
時間枠：Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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%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. |
Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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Amount of Enlicitide Decanoate Excreted in Urine From 0 to 24 Hours (AE0-24) After Administration of Enlicitide Decanoate
時間枠：Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose
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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. |
Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours postdose
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Percentage of Unchanged Enlicitide Decanoate Excreted in Urine (Fe)
時間枠：Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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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. |
Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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Renal Clearance (CLr) of Enlicitide Decanoate
時間枠：Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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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. |
Predose and 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, and 48 hours postdose
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Number of Participants Who Experienced an Adverse Event (AE)
時間枠：Up to approximately 30 days
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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. |
Up to approximately 30 days
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Panels A, B, and D: Number of Participants Who Discontinued From the Study Due to an AE
時間枠：Up to approximately 30 days
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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. |
Up to approximately 30 days
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Panel C: Number of Participants Who Discontinued From the Study Treatment Due to an AE
時間枠：Up to approximately 30 days
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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. |
Up to approximately 30 days
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協力者と研究者
スポンサー
捜査官
- スタディディレクター：Medical Director、Merck Sharp & Dohme LLC
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- 0616-020
- MK-0616-020 (その他の識別子：MSD)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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