A Study of Single Dose MK-3614 (MK-3614-001)(COMPLETED)
24 juni 2019 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
24
Fas
- Fas 1
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 55 år (Vuxen)
Tar emot friska volontärer
Ja
Kön som är behöriga för studier
Manlig
Beskrivning
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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.
|
|
|
Experimentell: 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
|
|
|
Experimentell: 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
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Percentage of Participants Who Reported 1 or More Adverse Event (AE) - Healthy Participants
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 0.25 mg MK-3614 - Healthy Participants- Fasted Versus Fed
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
1 november 2008
Primärt slutförande (Faktisk)
1 maj 2009
Avslutad studie (Faktisk)
1 maj 2009
Studieregistreringsdatum
Först inskickad
13 april 2010
Först inskickad som uppfyllde QC-kriterierna
13 april 2010
Första postat (Uppskatta)
15 april 2010
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
8 augusti 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
24 juni 2019
Senast verifierad
1 juni 2019
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 3614-001
- MK-3614-001 (Annan identifierare: Merck)
- 2010_525
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
JA
IPD-planbeskrivning
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .