A Randomized, Double-Blind, Placebo-Controlled, Combined Single Ascending Dose and Multiple Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of Intravenous Infusions of E2814 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- E2814
- Conditions
- Healthy Volunteers
- Sponsor
- Eisai Inc.
- Enrollment
- 72
- Locations
- 2
- Primary Endpoint
- MAD, Number of Participants With Clinically Significant Laboratory Values
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The primary objective of this study is to evaluate the safety and tolerability of single and multiple intravenous infusions of E2814 in healthy adult participants.
Detailed Description
The study is comprised of two components: a single ascending dose (SAD) component and a multiple ascending dose (MAD) component. The SAD component consists of 5 sequential cohorts and in each cohort, 8 healthy participants are randomized (3:1) to receive a single dose of E2814 or E2814-matched placebo. The MAD component of the study consists of 4 sequential cohorts and in each cohort, 8 healthy participants are randomized (3:1) to receive E2814 or E2814-matched placebo every 4 weeks (Q4W) on 3 occasions.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Nonsmoking, healthy participants.
- •Japanese participants must satisfy the following requirements:
- •Must have been born in Japan to Japanese parents and Japanese grandparents
- •Must have lived no more than 5 years outside of Japan
- •Must not have changed their life style or habits, including diet, while living outside of Japan
Exclusion Criteria
- •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
- •Females of childbearing potential who within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
- •total abstinence (if it is their preferred and usual lifestyle)
- •an intrauterine device or intrauterine hormone-releasing system
- •a contraceptive implant
- •an oral contraceptive (Participants must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 16 weeks after study drug discontinuation)
- •have a vasectomized partner with confirmed azoospermia Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 16 weeks after study drug discontinuation NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
- •Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation). If the female partner is pregnant, then males who do not agree to use latex, or synthetic condoms throughout the study period and for 90 days after study drug discontinuation. No sperm donation is allowed during the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation
- •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
Arms & Interventions
SAD, Cohort 1: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814
SAD, Cohort 1: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814-matched placebo
SAD, Cohort 2: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814-matched placebo
SAD, Cohort 2: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814
SAD, Cohort 3: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814
SAD, Cohort 3: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814-matched placebo
SAD, Cohort 4: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814
SAD, Cohort 4: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814-matched placebo
SAD, Cohort 5: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814
SAD, Cohort 5: E2814 or E2814-matched Placebo
Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.
Intervention: E2814-matched placebo
MAD, Cohort 1: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814
MAD, Cohort 1: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814-matched placebo
MAD, Cohort 2: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814
MAD, Cohort 2: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814-matched placebo
MAD, Cohort 3: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814
MAD, Cohort 3: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814-matched placebo
MAD, Cohort 4: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814
MAD, Cohort 4: E2814 or E2814-matched Placebo
Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.
Intervention: E2814-matched placebo
Outcomes
Primary Outcomes
MAD, Number of Participants With Clinically Significant Laboratory Values
Time Frame: Up to 169 days
SAD, Number of Participants With Clinically Significant Laboratory Values
Time Frame: Up to 113 days
SAD, Number of Participants With Clinically Significant Vital Signs Values
Time Frame: Up to 113 days
MAD, Number of Participants With TEAEs and SAEs
Time Frame: Up to 169 days
SAD, Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 113 days
SAD, Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
Time Frame: Up to 113 days
MAD, Number of Participants With Clinically Significant Vital Signs Values
Time Frame: Up to 169 days
MAD, Number of Participants With Clinically Significant ECG Findings
Time Frame: Up to 169 days
Secondary Outcomes
- SAD, Tmax Plasma: Time to Reach the Maximum Observed Concentration (Cmax) for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, t½ Plasma: Terminal Elimination Phase Half-life for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, CL Plasma: Clearance for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, Vz Plasma: Volume of Distribution for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, Plasma anti-E2814 Antibody Concentration(Pre-dose (Day 1) and up to Day 113 Post Dose)
- MAD, Cmax Serum: Maximum Observed Concentration for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- SAD, AUC (0-24h) Serum: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814(Pre-dose (Day 1) and up to 24 hours Post Dose)
- SAD, AUC (0-72h) Serum: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814(Pre-dose (Day 1) and up to 72 hours Post Dose)
- SAD, AUC (0-inf) Serum: Area Under the Concentration-time Curve from Time 0 to Infinity for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, t½ Serum: Terminal Elimination Phase Half-life for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, CL Serum: Clearance for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, AUC (0-24h) Plasma: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814(Pre-dose (Day 1) and up to 24 hours Post Dose)
- SAD, Cmax Serum: Maximum Observed Concentration for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, Tmax Serum: Time to Reach the Maximum Observed Concentration (Cmax) for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, Vz Serum: Volume of Distribution for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, Serum anti-E2814 Antibody Concentration(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, Cmax CSF: Maximum Observed Concentration for E2814(Pre-dose (Day 1) and up to Day 29 Post Dose)
- SAD, Tmax CSF: Time to Reach the Maximum Observed Concentration (Cmax) for E2814(Pre-dose (Day 1) and up to Day 29 Post Dose)
- SAD, AUC (0-24h) CSF: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814(Pre-dose (Day 1) and up to 24 hours Post Dose)
- SAD, Cmax Plasma: Maximum Observed Concentration for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- SAD, AUC (0-72h) Plasma: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814(Pre-dose (Day 1) and up to 72 hours Post Dose)
- SAD, AUC (0-inf) Plasma: Area Under the Concentration-time Curve from Time 0 to Infinity for E2814(Pre-dose (Day 1) and up to Day 113 Post Dose)
- MAD, Tmax Serum: Time to Reach the Maximum Observed Concentration (Cmax) for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, AUC (0-24h) Serum: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814(Pre-dose (Day 1) and up to 24 hours Post Dose)
- MAD, AUC (0-72h) Serum: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814(Pre-dose (Day 1) and up to 72 hours Post Dose)
- MAD, AUC (0-tau) Serum: Area Under the Concentration-time Curve From Zero Time to the end of the Dosing Interval for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, t½ Serum: Terminal Elimination Half-life for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, CL Serum: Clearance for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Vz Serum: Volume of Distribution for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Rac(Cmax) Serum: Ratio of Accumulation for Cmax for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Rac(AUC) Serum: Ratio of Accumulation for AUC for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Serum anti-E2814 Antibody Concentration(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, CSF Concentration for E2814(Pre-dose (Day 1) and up to Day 85 Post Dose)
- MAD, Cmax Plasma: Maximum Observed Concentration for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Tmax Plasma: Time to Reach the Maximum Observed Concentration (Cmax) for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, AUC (0-24h) Plasma: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814(Pre-dose (Day 1) and up to 24 hours Post Dose)
- MAD, AUC (0-72h) Plasma: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814(Pre-dose (Day 1) and up to 72 hours Post Dose)
- MAD, AUC (0-tau) Plasma: Area Under the Concentration-time Curve From Zero Time to the end of the Dosing Interval for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, t½ Plasma: Terminal Elimination Half-life for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, CL Plasma: Clearance for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Vz Plasma: Volume of Distribution for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Rac(Cmax) Plasma: Ratio of Accumulation for Cmax for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Rac(AUC) Plasma: Ratio of Accumulation for AUC for E2814(Pre-dose (Day 1) and up to Day 169 Post Dose)
- MAD, Plasma anti-E2814 Antibody Concentration(Pre-dose (Day 1) and up to Day 169 Post Dose)