Healthy ParticipantsPhase 1NCT02415790
Study to Assess the Safety, Tolerability, Pharmacokinetics of E2027 in Healthy Adult and Elderly Subjects, and the Pharmacodynamics in Healthy Adult Subjects
A Phase 1 study testing E2027 in people with Healthy Participants, run by Eisai Inc. at 1 site in United States.
Trial summary
This first-in-human study, designed to assess the safety, tolerability, and pharmacokinetics (PK) of single oral ascending doses of E2027, will be administered to healthy adult participants to determine the maximum tolerated dose (MTD). Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- E2027
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Part A and B only:
- Nonsmoking, male or female, age greater than or equal to 18 years and less than or equal to 50 years old at the time of informed consent
- Part C only:
- Nonsmoking, male or female, age greater than or equal to 65 years and less than or equal to 85 years old at the time of informed consent
- Part D only:
- Nonsmoking, male or female, age greater than or equal to 20 years and less than or equal to 50 years old at the time of informed consent
Show all 11Show fewer
- Born in Japan to Japanese parents and grandparents of Japanese descent
- Been living outside Japan for less than 5 years
- Lifestyle, including diet, has not changed significantly since leaving Japan
- All parts:
- Body mass index (BMI) greater than or equal to 18 and less than or equal to 30 kg/m2 at Screening
Who cannot join
- Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
- Females who are breastfeeding or pregnant at Screening or Baseline
- If females of childbearing potential who:
- Had unprotected sexual intercourse within 30 days before study entry and do not agree to use a highly effective method of contraception
- Are currently abstinent, and do not agree to use a double barrier method or refrain from sexual activity
- Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above. No sperm donation is allowed during the study period or for 28 days after study drug discontinuation.
Show all 30Show fewer
- Evidence of disease that may influence the outcome of the study within 4 weeks before dosing
- Any history of abdominal surgery that may affect PK profiles of E2027
- Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that requires medical treatment at Screening or Baseline
- A prolonged QT/QTc interval (QTc greater than 450 ms) demonstrated on ECG at Screening or Baseline
- Persistent systolic blood pressure greater than 130 mmHg or diastolic blood pressure greater than 85 mm Hg at Screening or Baseline (Parts A, B, and D)
- Persistent systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mm Hg at Screening or Baseline (Part C)
- Heart rate less than 50 or more than 100 beats/min at Screening or Baseline
- History of prolonged QT/QTc interval
- Left bundle branch block
- History of myocardial infarction or active ischemic heart disease
- History of clinically significant arrhythmia or uncontrolled arrhythmia
- Known history of clinically significant drug allergy at Screening or Baseline
- Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline
- Known to be human immunodeficiency virus (HIV) positive at Screening
- Active viral hepatitis (A, B or C) as demonstrated by positive serology at Screening
- History of drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive urine drug or alcohol test at Screening or Baseline
- Intake of caffeinated beverages or food within 72 hours before dosing
- Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug metabolizing enzymes and transporters within 1 week before dosing
- Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing
- Use of prescription drugs within 4 weeks before dosing
- Intake of over-the-counter (OTC) medications within 2 weeks before dosing
- Currently enrolled in another clinical trial or used any investigational drug or device within 30 days (or 5 half-lives, whichever is longer) preceding informed consent
- Engagement in strenuous exercise within 2 weeks before check-in (eg, marathon runners, weight lifters, etc.)
- Any contraindication to continuous CSF sampling via indwelling lumbar catheter (Part B only)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A 4-Part, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics of E2027 in Healthy Adult, Elderly and Japanese Subjects, and the Pharmacodynamics in Healthy Adult Subjects
This first-in-human study, designed to assess the safety, tolerability, and pharmacokinetics (PK) of single oral ascending doses of E2027, will be administered to healthy adult participants to determine the maximum tolerated dose (MTD). Thereafter, the pharmacodynamic (PD) effects of single doses of E2027 on elevation of cerebrospinal fluid (CSF) cyclic guanidine monophosphate (cGMP) in healthy adult participants will be evaluated across a broad dose range, to establish the PK/PD relationship.
Read the detailed description
The study will consist of 4 parts, Parts A, B, C, and D. Part A is a single ascending dose (SAD) clinical pharmacology for evaluation of safety, tolerability, and PK characteristics up to the MTD in healthy adult (greater than or equal to 18 years and less than or equal to 50 years old). In Part B, the PK and PD effects of E2027 on CSF cGMP are evaluated in healthy adult (greater than or equal to 18 years and less than or equal to 50 years old). Participants in 2nd cohort of Part B will participate in the evaluation of food effect in Treatment Period 2. In Part C, the design is similar to Part A. This healthy elderly cohort (greater than or equal to 65 years and less than or equal to 85 years old) will provide bridging PK, safety, and tolerability data on E2027 compared to younger healthy participants in Part A and Part B. Part D will be conducted in healthy Japanese adult participants (greater than or equal to 20 years and less than or equal to 50 years old) and is designed to bridge the PK, safety, and tolerability data of E2027 between Japanese and non-Japanese participants. All parts of the study will have 2 phases: the Prerandomization Phase and the Randomization Phase. The Prerandomization Phase will consist of a Screening Period and a Baseline Period during which each participant's study eligibility will be determined and baseline assessments will be conducted. The Randomization Phase will consist of the Treatment Period and a Follow-Up Period. During the Treatment Period, participants will be randomized to receive a single oral dose of either E2027 or placebo matching E2027.
- Conditions
- Healthy Participants
- Being tested
- E2027, E2027 matching placebo
- Keywords
- E2027, Healthy Adult and Elderly Subjects, Pharmacokinetics/Pharmacodynamics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E2027Drug
Part A: E2027 capsules will be administered orally in doses of 10 mg to 1200 mg in Part A and in Part B, C, and D at doses not exceeding the highest dose achieved in Part A.
E2027 matching placeboDrug
E2027 matching placebo capsule will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Part A: PK of E2027 in healthy adults | Experimental | Part A consists of 6 sequential cohorts of healthy adults. There will be 8 participants in each cohort, with 6 participants randomized to E2027 and 2 participants to placebo. Receives: Drug: E2027; Drug: E2027 matching placebo |
| Part B: PK and PD of E2027 in healthy adults | Experimental | Part B consists of 4 sequential cohorts of healthy adult participants. There will be 8 participants in the 1st cohort, with 6 participants randomized to E2027 and 2 participants to placebo. In the 2nd to 4th cohorts, there will be 7 participants in each cohort, with 6 participants randomized to E2027 and 1 participant to placebo. Participants in the 2nd cohort will then receive placebo/the same dose of E2027 again after their washout period in the fed state for the evaluation of food effect. Receives: Drug: E2027; Drug: E2027 matching placebo |
| Part C: PK of E2027 in elderly cohorts | Experimental | In Part C, 1 cohort of 8 healthy elderly participants will be enrolled, with 6 participants randomized to E2027 and 2 participants to placebo. Receives: Drug: E2027; Drug: E2027 matching placebo |
| Part D: PK of E2027 in healthy Japanese adults | Experimental | In Part D, there will be 3 cohorts of 7 healthy adult Japanese participants, with 6 participants randomized to E2027 and 1 participant to placebo. Receives: Drug: E2027; Drug: E2027 matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From screening up to 10 days
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - Cmax (maximum drug concentration)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Measured: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - tmax (time to reach maximum (peak) concentration following drug administration)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Measured: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - AUC (area under the concentration-time curve)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Measured: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - t1/2 (terminal elimination half-life following last dose)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Measured: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - CL/F (Apparent total clearance following extravascular (eg, oral) administration)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B and Part C - AUC Metabolite Ratio (Metabolite to E2027 ratio for AUC(0-inf) following molecular weight correction)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Measured: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - Vz/F (Apparent volume of distribution at terminal phase)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Measured: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - AUC Metabolite Ratio (Metabolite to E2027 ratio for AUC following molecular weight correction)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Measured: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (part A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Urine PK assessments of E2027 and its metabolites for Part A and Part C - Ae (cumulative amount of drug excreted in urine up to 96 hours postdose)
Measured: Day 1 to Day 5 postdose at 0 to 4 hours and greater than 4 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours and 72 to 96 hours
Urine PK assessments of E2027 and its metabolites for Part A and Part C - CLR (renal clearance)
Measured: Day 1 to Day 5 postdose at 0 to 4 hours and greater than 4 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours and 72 to 96 hours
CSF PK assessments of E2027 and its metabolites for Part B - Cmax (maximum drug concentration)
Measured: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - tmax (time to reach maximum (peak) concentration following drug administration)
Measured: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - AUC (area under the concentration-time curve from zero time extrapolated to infinite time)
Measured: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - t1/2 (terminal elimination half-life following last dose)
Measured: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - CSF:plasma ratio (ratio of AUC for CSF:plasma)
Measured: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - change from baseline in CSF cGMP
Measured: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - Amax (maximum change (%) of CSF cGMP concentration compared to baseline at a single time point within 30 hours postdose)
Measured: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - tAmax (time at which Amax occurs for CSF cGMP)
Measured: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - AUAC(-3 - 0 h) (area under the CSF cGMP concentration x time curve from time - 3 h to 0 h)
Measured: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - AUAC(0 -30 h) (Area under the CSF cGMP concentration x time curve from time 0 h to 30 h)
Measured: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B -Delta AUAC(0 - 30 h) (Change (%) in AUAC averaged over 30 hours postdose relative to baseline AUAC averaged over 3 h predose for CSF cGMP, i.e. (AUAC(0 - 30 h)/30 minus AUAC(-3 - 0 h)/3)/(AUAC(-3 - 0 h)/3)
Measured: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2015 (estimated)
- Study startJul 2015
- Primary completionJun 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02415790
- Sponsor's protocol ID
- E2027-A001-001
- Status last verified
- Mar 2017
- First submitted
- 11 Mar 2015
- Last updated
- 8 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 4-Part, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics of E2027 in Healthy Adult, Elderly and Japanese Subjects, and the Pharmacodynamics in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02415790
- Acronym / sponsor ID
- E2027-A001-001
- Conditions
- Healthy Participants
- Keywords
- E2027, Healthy Adult and Elderly Subjects, Pharmacokinetics/Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Jul 2015 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 14 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This first-in-human study, designed to assess the safety, tolerability, and pharmacokinetics (PK) of single oral ascending doses of E2027, will be administered to healthy adult participants to determine the maximum tolerated dose (MTD). Thereafter, the pharmacodynamic (PD) effects of single doses of E2027 on elevation of cerebrospinal fluid (CSF) cyclic guanidine monophosphate (cGMP) in healthy adult participants will be evaluated across a broad dose range, to establish the PK/PD relationship.
Detailed description
The study will consist of 4 parts, Parts A, B, C, and D. Part A is a single ascending dose (SAD) clinical pharmacology for evaluation of safety, tolerability, and PK characteristics up to the MTD in healthy adult (greater than or equal to 18 years and less than or equal to 50 years old). In Part B, the PK and PD effects of E2027 on CSF cGMP are evaluated in healthy adult (greater than or equal to 18 years and less than or equal to 50 years old). Participants in 2nd cohort of Part B will participate in the evaluation of food effect in Treatment Period 2. In Part C, the design is similar to Part A. This healthy elderly cohort (greater than or equal to 65 years and less than or equal to 85 years old) will provide bridging PK, safety, and tolerability data on E2027 compared to younger healthy participants in Part A and Part B. Part D will be conducted in healthy Japanese adult participants (greater than or equal to 20 years and less than or equal to 50 years old) and is designed to bridge the PK, safety, and tolerability data of E2027 between Japanese and non-Japanese participants. All parts of the study will have 2 phases: the Prerandomization Phase and the Randomization Phase. The Prerandomization Phase will consist of a Screening Period and a Baseline Period during which each participant's study eligibility will be determined and baseline assessments will be conducted. The Randomization Phase will consist of the Treatment Period and a Follow-Up Period. During the Treatment Period, participants will be randomized to receive a single oral dose of either E2027 or placebo matching E2027.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A: PK of E2027 in healthy adults | Experimental | Drug: E2027, Drug: E2027 matching placeboPart A consists of 6 sequential cohorts of healthy adults. There will be 8 participants in each cohort, with 6 participants randomized to E2027 and 2 participants to placebo. |
| Part B: PK and PD of E2027 in healthy adults | Experimental | Drug: E2027, Drug: E2027 matching placeboPart B consists of 4 sequential cohorts of healthy adult participants. There will be 8 participants in the 1st cohort, with 6 participants randomized to E2027 and 2 participants to placebo. In the 2nd to 4th cohorts, there will be 7 participants in each cohort, with 6 participants randomized to E2027 and 1 participant to placebo. Participants in the 2nd cohort will then receive placebo/the same dose of E2027 again after their washout period in the fed state for the evaluation of food effect. |
| Part C: PK of E2027 in elderly cohorts | Experimental | Drug: E2027, Drug: E2027 matching placeboIn Part C, 1 cohort of 8 healthy elderly participants will be enrolled, with 6 participants randomized to E2027 and 2 participants to placebo. |
| Part D: PK of E2027 in healthy Japanese adults | Experimental | Drug: E2027, Drug: E2027 matching placeboIn Part D, there will be 3 cohorts of 7 healthy adult Japanese participants, with 6 participants randomized to E2027 and 1 participant to placebo. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Nonsmoking, male or female, age greater than or equal to 18 years and less than or equal to 50 years old at the time of informed consent
- Nonsmoking, male or female, age greater than or equal to 65 years and less than or equal to 85 years old at the time of informed consent
- Nonsmoking, male or female, age greater than or equal to 20 years and less than or equal to 50 years old at the time of informed consent
- Born in Japan to Japanese parents and grandparents of Japanese descent
- Been living outside Japan for less than 5 years
Key exclusion criteria (30 listed)
- Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
- Females who are breastfeeding or pregnant at Screening or Baseline
- If females of childbearing potential who:
- Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above. No sperm donation is allowed during the study period or for 28 days after study drug discontinuation.
- Evidence of disease that may influence the outcome of the study within 4 weeks before dosing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E2027Part A: E2027 capsules will be administered orally in doses of 10 mg to 1200 mg in Part A and in Part B, C, and D at doses not exceeding the highest dose achieved in Part A. | Drug | Part A: PK of E2027 in healthy adults, Part B: PK and PD of E2027 in healthy adults, Part C: PK of E2027 in elderly cohorts, Part D: PK of E2027 in healthy Japanese adults |
| E2027 matching placeboE2027 matching placebo capsule will be administered. | Drug | Part A: PK of E2027 in healthy adults, Part B: PK and PD of E2027 in healthy adults, Part C: PK of E2027 in elderly cohorts, Part D: PK of E2027 in healthy Japanese adults |
Primary outcome
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From screening up to 10 days
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - Cmax (maximum drug concentration)
Time frame: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - tmax (time to reach maximum (peak) concentration following drug administration)
Time frame: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - AUC (area under the concentration-time curve)
Time frame: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - t1/2 (terminal elimination half-life following last dose)
Time frame: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - CL/F (Apparent total clearance following extravascular (eg, oral) administration)
Time frame: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
Plasma PK assessments of E2027 and its metabolites for Part A, Part B and Part C - AUC Metabolite Ratio (Metabolite to E2027 ratio for AUC(0-inf) following molecular weight correction) For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - Vz/F (Apparent volume of distribution at terminal phase)
Time frame: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (parts A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Plasma PK assessments of E2027 and its metabolites for Part A, Part B, Part C, and Part D - AUC Metabolite Ratio (Metabolite to E2027 ratio for AUC following molecular weight correction)
Time frame: Day 1 at predose and postdose 0.5 (30 minutes) to 18 hours, postdose on Day 2 (24 and 36 hours (part A, B, C, D) and 30 hours (part B only), Day 3 (48 hours), Day 4 (72 hours), Day 5, (96 hours), Day 6 (120 hours), Day 7 (144 hours), Day 10 (216 hours)
For participants in Part B of the 2nd cohort only, samples will also be collected on the following days of Treatment Period 2: Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 18 hours. Participants will receive a single oral dose of the same study drug that they received in the previous treatment period, but after a high-fat meal.
Urine PK assessments of E2027 and its metabolites for Part A and Part C - Ae (cumulative amount of drug excreted in urine up to 96 hours postdose)
Time frame: Day 1 to Day 5 postdose at 0 to 4 hours and greater than 4 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours and 72 to 96 hours
Urine PK assessments of E2027 and its metabolites for Part A and Part C - CLR (renal clearance)
Time frame: Day 1 to Day 5 postdose at 0 to 4 hours and greater than 4 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 48 hours, 48 to 72 hours and 72 to 96 hours
CSF PK assessments of E2027 and its metabolites for Part B - Cmax (maximum drug concentration)
Time frame: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - tmax (time to reach maximum (peak) concentration following drug administration)
Time frame: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - AUC (area under the concentration-time curve from zero time extrapolated to infinite time)
Time frame: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - t1/2 (terminal elimination half-life following last dose)
Time frame: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
CSF PK assessments of E2027 and its metabolites for Part B - CSF:plasma ratio (ratio of AUC for CSF:plasma)
Time frame: At predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - change from baseline in CSF cGMP
Time frame: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - Amax (maximum change (%) of CSF cGMP concentration compared to baseline at a single time point within 30 hours postdose)
Time frame: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - tAmax (time at which Amax occurs for CSF cGMP)
Time frame: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - AUAC(-3 - 0 h) (area under the CSF cGMP concentration x time curve from time - 3 h to 0 h)
Time frame: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B - AUAC(0 -30 h) (Area under the CSF cGMP concentration x time curve from time 0 h to 30 h)
Time frame: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
PD assessments for Part B -Delta AUAC(0 - 30 h) (Change (%) in AUAC averaged over 30 hours postdose relative to baseline AUAC averaged over 3 h predose for CSF cGMP, i.e. (AUAC(0 - 30 h)/30 minus AUAC(-3 - 0 h)/3)/(AUAC(-3 - 0 h)/3)
Time frame: At -3, - 2, -1 hours, predose (0 hour), and postdose at 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 24 and 30 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E2027 in people with Healthy Participants, run by Eisai Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From screening up to 10 days). The study lists 21 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2017.