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A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED)

24 juin 2019 mis à jour par: Merck Sharp & Dohme LLC

A Single Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-3614

This study will determine if MK-3614, given as single doses, is safe and well tolerated in healthy males and male participants with mild to moderate hypertension.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

Up to three planned panels of either 8 healthy participants (Panels A and B) or 8 participants with mild to moderate hypertension (Panel C) will be enrolled. In Panels A and B, 8 participants will alternately receive single rising doses of MK-3614 or placebo. All doses will be administered in the fasted state, except Panel A, Period 3 in which a standard high-fat breakfast provided approximately 30 minutes prior to dosing. Panel A will begin first. At least 3 days will elapse before participants in the alternate panel (Panel B) will receive the next higher dose. In Panel C, 8 mild to moderate hypertensive male participants will receive single rising doses of MK-8892 or placebo. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. All participants in periods of all panels (with exception of 0.25 mg fasted/fed periods) will be randomly assigned to either study drug or placebo, i.e., a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants will receive 0.25 mg MK-3612 in a fasted and fed state.

Type d'étude

Interventionnel

Inscription (Réel)

24

Phase

  • La phase 1

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 55 ans (Adulte)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Homme

La description

Inclusion Criteria:

  • Healthy participants between 18 to 45 years of age; otherwise healthy participants between 18 to 55 years of age newly diagnosed with grade 1 or 2 hypertension
  • Participant is in good general health
  • Participant is a nonsmoker

Exclusion Criteria:

  • Participant has a history of stroke, seizure or major neurological disease
  • Participant has functional disability that can interfere with rising from a sitting position to a standing position
  • Participant has a family history of a bleeding or clotting disorder
  • Participant has a history of cancer
  • Participant is unable to refrain from or anticipates the use of any prescription or non-prescription medication during the study
  • Participant consumes excessive amounts of alcohol or caffeine
  • Participant has had major surgery, donated blood or participated in another investigational study in the past 4 weeks.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Panel A - Healthy
Healthy participants receive single oral dose of MK-3614 0.25 mg, 1.25 mg, 0.25 mg w/ food, 0.75 mg or matching placebo. There is at least a 7-day washout between the 4 dosing periods. All doses were administered after an 8-hour fast except for Period 3. Period 3 dose was administered after the ingestion of a high-fat breakfast.
Médicament: Comparateur : Placebo
Médicament: MK-3614
Expérimental: Panel B - Healthy
Healthy participants receive single oral dose of MK-3614 0.5 mg. 0.75 mg, 0.25 mg twice a day (b.i.d.), 0.25 mg three times a day (t.i.d), or matching placebo. There is at least a 7-day washout between the 4 dosing periods. All doses were administered after an 8-hour fast
Médicament: Comparateur : Placebo
Médicament: MK-3614
Expérimental: Panel C - Hypertensive
Hypertensive participants receive single oral dose of MK-3614 0.75 mg. 0.5 mg. 0.75 mg, 0.75 mg or matching placebo. There is at least a 7-day washout between the 4 dosing period. All doses were administered after an 8-hour fast
Médicament: Comparateur : Placebo
Médicament: MK-3614

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants
Délai: up to 7 days for each dose level
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. AEs are reported by the dose taken at the time of the event.
up to 7 days for each dose level
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Healthy Participants
Délai: up to 7 days for each dose level
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who were discontinued from the study due to an AE were summarized. AEs are reported by the dose taken at the time of the event.
up to 7 days for each dose level
Percentage of Participants Who Report 1 or More Adverse Event (AE) - Hypertensive Participants
Délai: up to 7 days for each dose level
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. The percentage of participants that reported at least 1 AE was summarized. AEs are reported by the dose taken at the time of the event.
up to 7 days for each dose level
Percentage of Participants Who Were Discontinued From the Study Due to an AE - Hypertensive Participants
Délai: up to 7 days for each dose level
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who were discontinued from the study due to an AE were summarized. AEs are reported by the dose taken at the time of the event.
up to 7 days for each dose level
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Healthy Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of MK-3614 in healthy participants.
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Maximum Concentration (Cmax) of MK-3614- Healthy Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of MK-3614 in healthy participants.
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Time to Cmax (Tmax) of MK-3614- Healthy Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Tmax of MK-3614 in healthy participants.
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Apparent Terminal Half-life (t1/2) of MK-3614- Healthy Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the t1/2 of MK-3614 in healthy participants.
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-3614 - Hypertensive Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of MK-3614 in hypertensive participants
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Maximum Concentration (Cmax) of MK-3614- Hypertensive Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of MK-3614 in hypertensive participants
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Time to Cmax (Tmax) of MK-3614- Hypertensive Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Tmax of MK-3614 in hypertensive participants
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Apparent Terminal Half-life (t1/2) of MK-3614 of MK-3614- Hypertensive Participants
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the t1/2 of MK-3614 in hypertensive participants
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Change From Baseline in Heart Rate - Healthy Participants
Délai: Baseline and 24 hours post-dose for each dose level
Heart rate measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.
Baseline and 24 hours post-dose for each dose level
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Healthy Participants
Délai: Baseline and 24 hours postdose for each dose level
Brachial arterial systolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.
Baseline and 24 hours postdose for each dose level
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Healthy Participants
Délai: Baseline and 24 hours postdose for each dose level
Brachial arterial diastolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.
Baseline and 24 hours postdose for each dose level
Change From Baseline in Heart Rate - Hypertensive Participants
Délai: Baseline and 24 hours postdose for each dose level
HR measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of sequence.
Baseline and 24 hours postdose for each dose level
Change From Baseline in Brachial Arterial Systolic Blood Pressure - Hypertensive Participants
Délai: Baseline and 24 hours postdose for each dose level
Brachial arterial systolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of sequence.
Baseline and 24 hours postdose for each dose level
Change From Baseline in Brachial Arterial Diastolic Blood Pressure - Hypertensive Participants
Délai: Baseline and 24 hours postdose for each dose level
Brachial arterial diastolic blood pressure measurements were obtained using a validated, semi-automated oscillometric device. The difference between the predose (baseline) measurement and the measurement 24 obtained 24 hours postdose was summarized. Data for each specific dose were combined regardless of sequnce.
Baseline and 24 hours postdose for each dose level

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the AUC0-inf of 0.25 mg MK-3614 in healthy participant when administered after an 8 hour fast and after a high-fat breakfest.
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Maximum Concentration (Cmax) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
Délai: Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Blood samples taken at Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose of each dosing period to determine the Cmax of 0.25 mg MK-3614 when administered after an 8 hour fast and after a high-fat breakfest.
Predose, and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose for each dose level
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Healthy Participants
Délai: Baseline and 24 hours postdose for each dose level
Augmentation index was measured at predose (baseline), and 1, 4, 8, 12, and 24 hours postdose by aplanation tonometry of radial artery. The change from baseline at 24 hours postdose was summarized. Data for each specific dose were combined regardless of panel.
Baseline and 24 hours postdose for each dose level
Percentage Change From Baseline in Augmentation Index (AIx) at 24 Hours Postdose - Hypertensive Participants
Délai: Baseline and 24 hours postdose for each dose level
Augmentation index was measured at predose (baseline), and 1, 4, 8, 12, and 24 hours postdose by aplanation tonometry of radial artery. The change from baseline at 24 hours postdose was summarized.
Baseline and 24 hours postdose for each dose level
Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose - Healthy Participants
Délai: Baseline and 24 hours postdose for each dose level
Blood was to be drawn at predose (baseline) and 3 and 24 hours postdose and bleeding time was to be assessed using a Newborn Surgicutt device. Change in bleeding time from baseline at 24 hours postdose were to be summarized. Due to change in number of blood draws and total blood volume restrictions, bleeding time assessment was not performed as planned.
Baseline and 24 hours postdose for each dose level
Percentage Change From Baseline in Bleeding Time at 24 Hours Postdose- Hypertension Participants
Délai: Baseline and 24 hours postdose for each dose level
Blood was to be drawn at predose (baseline) and 3 and 24 hours postdose and bleeding time was to be assessed using a Newborn Surgicutt device. Change in bleeding time from baseline at 24 hours postdose were to be summarized. Due to change in number of blood draws and total blood volume restrictions, bleeding time assessment was not performed as planned.
Baseline and 24 hours postdose for each dose level
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Healthy Participants
Délai: Baseline and 24 hours postdose for each dose level
Blood was drawn at predose (baseline) and 1, 4, 8, and 24 hours postdose. The change in cyclic GMP at 24 hours postdose was summarized. Due to change in number of blood draws and total blood volume restrictions, data for GMP were only collected for first 2 periods of each panel. Therefore only limited data were available and summarized. Data for each specific dose were combined regardless of panel.
Baseline and 24 hours postdose for each dose level
Percentage Change in Cyclic Guanosine Monophosphate (GMP) From Baseline at 24 Hours Postdose - Hypertension Participants
Délai: Baseline and 24 hours postdose for each dose level
Blood was drawn at predose (baseline) and 1, 4, 8, and 24 hours postdose. The change in cyclic GMP at 24 hours postdose was summarized. Due to change in number of blood draws and total blood volume restrictions, data for GMP were only collected for first 2 periods of each panel. Therefore only limited data were available and summarized.
Baseline and 24 hours postdose for each dose level
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Healthy Participants
Délai: Baseline and 24 hours postdose for each dose level
Platelet aggregation induced by adenosine diphosphate (ADP) was measured at predose (baseline) and 3 and 24 hours postdose. Percent inhibition from baseline at 24 hours postdose was calculated. Due to change in number of blood draws and total blood volume restrictions, data for platelet aggregation were only collected for first 2 periods of each panel. Therefore only limited data were available and summarized. Data for each specific dose were combined regardless of panel.
Baseline and 24 hours postdose for each dose level
Percentage Change From Baseline in Platelet Aggregation at 24 Hours Postdose - Hypertensive Participants
Délai: Baseline and 24 hours postdose for each dose level
Platelet aggregation induced by adenosine diphosphate (ADP) was measured at predose (baseline) and 3 and 24 hours postdose. Percent inhibition from baseline at 24 hours postdose was calculated. Due to change in number of blood draws and total blood volume restrictions, data for platelet aggregation were only collected for first 2 periods of each panel. Therefore only limited data were available and summarized.
Baseline and 24 hours postdose for each dose level

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Merck Sharp & Dohme LLC

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 novembre 2008

Achèvement primaire (Réel)

1 mai 2009

Achèvement de l'étude (Réel)

1 mai 2009

Dates d'inscription aux études

Première soumission

13 avril 2010

Première soumission répondant aux critères de contrôle qualité

13 avril 2010

Première publication (Estimation)

15 avril 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

8 août 2019

Dernière mise à jour soumise répondant aux critères de contrôle qualité

24 juin 2019

Dernière vérification

1 juin 2019

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • 3614-001
  • MK-3614-001 (Autre identifiant: Merck)
  • 2010_525

Plan pour les données individuelles des participants (IPD)

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OUI

Description du régime IPD

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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