- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT05147337
A Study to Assess the Safety and Tolerability of E2511 in Healthy Adult and Elderly Participants
8. september 2022 opdateret af: Eisai Inc.
A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2511 in Healthy Adult and Elderly Subjects
The primary objective of this study is to evaluate the safety, tolerability, and plasma pharmacokinetic (PK) of E2511 following multiple oral doses in healthy adult participants.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
47
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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California
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Glendale, California, Forenede Stater, 91206
- California Clinical Trials Medical Group
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 85 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Non-smoking, male, or female, non-Japanese participants age >=18 years and <55 years old (Cohorts 1 to 4) or age >=55 years and <=85 years old (Cohort 8); or Japanese participants age >=20 years and <55 years old (Cohorts 5 to 7) at the time of informed consent
Japanese participants must also satisfy the following requirements:
- Must have been born in Japan of Japanese parents and Japanese grandparents
- Must have lived no more than 5 years outside of Japan
- Must not have changed their lifestyle or habits, including diet, while living outside of Japan
- Weight of at least 50 kilogram (kg) and body mass index (BMI) >=18 and <30 kilogram per square meter (kg/m^2) (Cohorts 1 to 7) or BMI >=18 and <32 kg/m^2 (Cohort 8) at Screening
Exclusion Criteria:
- Females who are breastfeeding or pregnant at Screening or Baseline
Females of childbearing potential who:
- Within 28 days before study entry, did not use a highly effective method of contraception
- Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation.
- Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
- Evidence of disease that may influence the outcome of the study within 4 weeks before dosing; example, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
- Evidence of disease within 4 weeks before dosing related to chronic headaches, migraines, joint pain, or other disorders or disease resulting in chronic or intermittent pain
- Any personal or family history of seizures (including febrile seizures) or diagnosis of epilepsy or episode of unexplained loss of consciousness
- Any history of neurological or other medical conditions which in the opinion of the investigator has the potential to reduce seizure threshold
- Any history of gastrointestinal surgery that may affect PK profiles of E2511, example, hepatectomy, nephrectomy, digestive organ resection at Screening
- Any clinically abnormal symptom or organ impairment found by medical history at Screening, and physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment at Screening or Baseline
- A prolonged QT/QT interval corrected for heart rate (QTc) interval or a prolonged QT/QTc interval (QT interval corrected for heart rate using Fridericia's formula [QTcF] greater than [>] 450 milliseconds [ms]). A history of risk factors for torsade de pointes
- HR <50 or more than 100 beats per minute at Screening or Baseline (Cohorts 1 through 7); or HR <55 or more than 100 beats per minute at Screening or Baseline (Cohort 8) NOTE: At Baseline, HR must meet the above criteria on 3 assessments (each separated by 15 minutes) to ensure eligibility
- Left bundle branch block
- History of myocardial infarction or active ischemic heart disease
- History of clinically significant arrhythmia or uncontrolled arrhythmia
- Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the C-SSRS
- Any lifetime history of psychiatric disease
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Andet
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Cohort 1: E2511 10 mg or Placebo
Non-Japanese adult (greater than or equal to [>=] 18 years and less than [<] 55 years old) participants will receive 10 milligram (mg) E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Eksperimentel: Cohort 2: E2511 20 mg or Placebo
Non-Japanese adult participants will receive 20 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Eksperimentel: Cohort 3: E2511 40 mg or Placebo
Non-Japanese adult participants will receive 40 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Eksperimentel: Cohort 4: E2511 80 mg or Placebo
Non-Japanese adult participants will receive 80 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Eksperimentel: Cohort 5: E2511 20 mg or Placebo
Japanese adult (>=20 years and <55 years old) participants will receive 20 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Eksperimentel: Cohort 6: E2511 40 mg or Placebo
Japanese adult participants will receive 40 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Eksperimentel: Cohort 7: E2511 80 mg or Placebo
Japanese adult participants will receive 80 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Eksperimentel: Cohort 8: E2511 40 mg or Placebo
Non-Japanese older (>=55 years and less than or equal to [<=] 85 years old) participants will receive 40 mg E2511 or E2511 matched placebo, tablets, orally, once daily from Day 1 to Day 14.
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E2511 tabletter.
E2511 matched placebo tablets.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Serious Adverse Events (SAEs)
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Clinically Significant Abnormal Laboratory Values
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Clinically Significant Abnormal Vital Signs Values
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Findings
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Clinically Significant Abnormal Ambulatory Blood Pressure
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-suicide Severity Rating Scale (C-SSRS)
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment [C-CASA]) is an interview-based rating scale to systematically assess any suicidality, suicidal behavior, or suicidal ideation.
Any suicidality is emergence of any suicidal ideation or suicidal behavior.
Any suicidal behavior is indicated when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts.
Any suicidal ideation is indicated when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Clinically Significant Abnormal Physical Examination Findings
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Clinically Significant Abnormal Neurological Examination Findings
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Number of Participants With Clinically Significant Abnormal Electroencephalogram (EEG) Findings
Tidsramme: From Screening up to 14 days after the last dose of study drug (up to 56 days)
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From Screening up to 14 days after the last dose of study drug (up to 56 days)
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Cmax: Maximum Observed Plasma Concentration for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose
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Css,max: Maximum Observed Plasma Concentration at Steady State for E2511
Tidsramme: Day 14: pre-dose up to 24 hours post-dose
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Day 14: pre-dose up to 24 hours post-dose
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tmax: Time to Reach Maximum Observed Plasma Concentration (Cmax) for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose
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tss,max: Time to Reach Maximum Observed Plasma Concentration (Cmax) at Steady State for E2511
Tidsramme: Day 14: pre-dose up to 24 hours post-dose
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Day 14: pre-dose up to 24 hours post-dose
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Css,av: Average Steady State Plasma Concentration for E2511
Tidsramme: Day 14: pre-dose up to 24 hours post-dose
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Day 14: pre-dose up to 24 hours post-dose
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AUC(0-t): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time Zero to Infinite for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose
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AUC(0-24h): Area Under the Plasma Concentration-time Curve From Time Zero to 24 hours Post-dose for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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t1/2: Terminal Elimination Phase Half-life for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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PTF: Peak-trough Fluctuation for E2511
Tidsramme: Day 14: pre-dose up to 24 hours post-dose
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Day 14: pre-dose up to 24 hours post-dose
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CL/F: Apparent Total Clearance for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose
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CLss/F: Apparent Total Clearance at Steady State for E2511
Tidsramme: Day 14: pre-dose up to 24 hours post-dose
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Day 14: pre-dose up to 24 hours post-dose
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Vz/F: Apparent Volume of Distribution at Terminal Phase for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Rac: Accumulation Ratio for E2511 Based on Cmax and AUC
Tidsramme: Day 14: pre-dose up to 24 hours post-dose
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Day 14: pre-dose up to 24 hours post-dose
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Rss: Accumulation Ratio for E2511 Based on Time and Concentration
Tidsramme: Day 14: pre-dose up to 24 hours post-dose
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Day 14: pre-dose up to 24 hours post-dose
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change From Baseline in the Concentration of Acetylcholine (ACh) in Cerebrospinal Fluid (CSF)
Tidsramme: Baseline, Day 13
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Baseline, Day 13
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Change From Baseline in Heart Rate (HR)
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Change From Baseline in PR Interval of the ECG (PR), QRS Interval of the ECG (QRS), and QT Interval Corrected for Heart Rate (QTc) of the ECG
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Placebo Corrected Change From Baseline in HR
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Placebo Corrected Change From Baseline in PR, QRS, and QTc Interval
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Number of Participants With Categorical Outliers for HR, PR, QRS and QTc Interval
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Number of Participants With Treatment-emergent T-wave and U-wave abnormalities
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Mean Change From Baseline in 24-hours Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) up to Day 15
Tidsramme: Up to Day 15
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The blood pressure (BP) will be evaluated by Ambulatory Blood Pressure Monitoring (ABPM) for all participants based on the measurement of BP recordings after every 24 hours.
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Up to Day 15
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Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Mean Change From Baseline in Day-time, Night-time, and Hourly HR
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Mean Change From Baseline in Day-time, Night-time, and Hourly Mean Arterial Pressure (MAP) and Pulse Pressure (PP)
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Placebo Corrected Mean Change From Baseline in 24-hours SBP and DBP up to Day 15
Tidsramme: Up to Day 15
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The BP will be evaluated by ABPM for all participants based on the measurement of BP recordings after every 24 hours.
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Up to Day 15
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Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly SBP and DBP
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly HR
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Placebo Corrected Mean Change From Baseline in Day-time, Night-time, and Hourly MAP and PP
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Number of Participants With Categorical Outliers for SBP and DBP
Tidsramme: Baseline up to Day 15
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Baseline up to Day 15
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Geometric Mean Ratio of Cmax Between the Healthy Japanese and Non-japanese Participants for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Geometric Mean Ratio of AUC Between the Healthy Japanese and Non-japanese Participants for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Geometric Mean Ratio of Cmax Between the Younger Non-japanese (>=18 and <55 years) and older Non-japanese (>=55 to <=85 years) Participants for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Geometric Mean Ratio of AUC Between the Younger Non-japanese (>=18 and <55 years) and older Non-japanese (>=55 to <=85 years) Participants for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Geometric Mean Ratio Between the Non-japanese (>=18 and <55 years) and Elderly Non-japanese (>=65 to <=85 years) Participants for E2511
Tidsramme: Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Day 1: pre-dose up to 24 hours post-dose; Day 14: pre-dose up to 24 hours post-dose
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
1. december 2021
Primær færdiggørelse (Faktiske)
18. august 2022
Studieafslutning (Faktiske)
18. august 2022
Datoer for studieregistrering
Først indsendt
24. november 2021
Først indsendt, der opfyldte QC-kriterier
24. november 2021
Først opslået (Faktiske)
7. december 2021
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
9. september 2022
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
8. september 2022
Sidst verificeret
1. marts 2022
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Andre undersøgelses-id-numre
- E2511-A001-005
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
JA
IPD-planbeskrivelse
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med E2511
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Eisai Inc.AfsluttetSunde frivilligeForenede Stater