臨床研究等提出・公開システム

Phase 1 study of EA3571 in healthy adult subjects

Phase 1 study of EA3571 in healthy adult subjects

165

-SAD Part- The mean (SD) ages ranged from 24.7 (3.93) to 28.1 (7.13) years in Part 1 (Japanese) and from 25.0 (3.35) to 37.8 (5.67) years in Part 2 (Caucasian). The mean weight (SD) ranged from 58.25 (2.696) to 69.62 (3.544) kg in Part 1 and from 73.03 (7.260) to 81.50 (8.031) kg in Part 2. The mean BMI (SD) ranged from 20.23 (1.344) to 23.08 (1.179) kg/m2 in Part 1 and from 23.23 (1.763) to 24.70 (3.348) kg/m2 in Part 2. -Gelatin Load Test Part- The mean (SD) ages ranged from 26.0 (3.46) to 36.0 (7.55) years in Part 3 (Japanese), from 27.3 (7.20) to 31.0 (8.85) years in Part 4 (Japanese), and from 29.2 (6.43) to 35.8 (11.14) years in Part 5 (Caucasian) . The mean weight (SD) ranged from 58.40 (6.809) to 62.27 (6.637) kg in Part 3, from 58.58 (5.811) to 65.82 (6.438) kg in Part 4, and from 72.50 (15.799) to 77.04 (9.760) kg in Part 5. The mean BMI (SD) ranged from 19.97 (1.457) to 22.47 (2.754) kg/m2 in Part 3, from 19.67 (1.325) to 22.25 (2.439) kg/m2 in Part 4, from 22.82 (4.467) to 24.84 (3.422) kg/m2 in Part 5. -MAD Part- The mean (SD) ages ranged from 28.0 (4.94) to 31.5 (4.89) years in Part 6 (Japanese) and from 22.8 (2.75) to 29.0 (6.90) years in Part 7 (Caucasian). The mean weight (SD) ranged from 60.92 (6.252) to 68.28 (6.081) kg in Part 6 and from 76.53 (7.130) to 78.95 (8.728) kg in Part 7. The mean BMI (SD) ranged from 21.10 (1.881) to 21.80 (1.066) kg/m2 in Part 6 and from 24.10 (2.974) to 25.03 (2.681) kg/m2 in Part 7. Overall, the demographic and baseline characteristics were comparable among any cohort in both parts.

-SAD Part- In Part 1, 64 Japanese subjects were divided into 8 cohorts (8 doses, Cohorts 1-1 to 1-8), with 8 subjects in each. In Part 2, 24 Caucasian subjects were divided into 3 cohorts (3 doses, Cohorts 2-1 to 2-3), with 8 subjects in each. In each cohort, 6 subjects were randomly assigned to the EA3571 group and 2 subjects to the placebo group. -Gelatin Load Test Part- Part 3 (Japanese, 2-group, 2-period crossover): In Part 3, 18 Japanese subjects were divided into 3 cohorts (3 doses: Cohorts 3-1 to 3-3) with 6 subjects in each. In each cohort, 3 subjects were randomly assigned to Group A (Tratment Period 1: immediately before breakfast, Period 2: after breakfast) and 3 subjects were randomly assigned to Group B (Period 1: after breakfast, Period 2: immediately before breakfast). On days 1 and 6, subjects received a single oral dose of EA3571 immediately before breakfast (5 minutes before breakfast start) or after breakfast (30 minutes after breakfast start), and gelatin was orally administered 15 minutes after breakfast start in the specified order. Part4 (Japanese) and Part5 (Caucasian): In Part 4, 12 Japanese subjects were divided into 2 cohorts (2 doses: Cohorts 4-1 and 4-2) with 6 subjects in each. In Part 5, 11 Caucasian subjects were divided into 2 cohorts (2 doses: Cohorts 5-1: 6 subjects, 5-2: 5 subjects). On days 1 and 6, subjects received a single oral dose of EA3571 immediately before breakfast (5 minutes before breakfast start) . For gelatin loading, gelatin was orally administered 15 minutes after the start of breakfast on day 1 (Period1) and 15 minutes after the start of lunch on day 6 (Period 2). -MAD Part- In Part 6, 24 Japanese subjects were divided into 3 cohorts (3 doses: Cohorts 6-1 to 6-3) with 8 subjects in each. In each cohort, 6 subjects were randomly assigned to the EA3571 group and 2 subjects to the placebo group. In Part 7, 9 Caucasian subjects were randomly assigned to the EA3571 group and 3 subjects to the placebo group. Subjects received EA3571 or placebo orally just before breakfast on Day 1, followed by a 2-day washout period, and then orally administered EA3571 or placebo 3 times daily 5 minutes before the start of breakfast, lunch, and dinner for 7 days from Day 4 to Day 10.

-SAD Part- Part 1: TEAEs were reported in 2 subjects (12.5%) in the placebo group, 1 subject (16.7%) in cohort 1-1 (10 mg), 1 subject (16.7%) in cohort 1-2 (30 mg), 1 subject (16.7%) in cohort 1-7 (800 mg), and 2 subjects (33.3%) in cohort 1-8 (1200 mg) in the EA3571 group. Part 2: TEAEs were reported in 1 subject (16.7%) each in cohort 2-1 (50 mg) and 2-3 (800 mg) in the EA3571 group. -Gelatin Load Test part- Part 3: TEAEs were reported in 1 subject (16.7%) in cohort 3-1 (50 mg). Part 4: TEAEs were reported in 1 subject (16.7%) each in cohorts 4-1 (200 mg) and 4-2 (50 mg). Part 5: TEAEs were reported in 2 subjects (33.3%) in cohort 5-1 (200 mg) and 1 subject (20.0%) in cohort 5-2 (50 mg). -MAD part- Part 6: TEAEs were reported in 1 subject (16.7%) in the placebo group, 1 subject (16.7%) in cohort 6-1 (50 mg), 3 subjects (50.0%) in cohort 6-2 (100 mg), and 4 subjects (66.7%) in cohort 6-3 (200 mg) in the EA3571 group. Part 7: One TEAE (25.0%) in the placebo group and 5 TEAEs (71.4%) in the EA3571 group in cohort 7-1 (200 mg) were reported. The most common TEAE was "occult blood positive" throughout the study. All the events of occult blood positive were mild and not considered related to the study treatment. No deaths, serious TEAEs, severe TEAEs, or TEAEs leading to discontinuation of investigational products or the study after treatment completion were reported. The majority of TEAEs were mild, and only 1 moderate TEAE (muscle enzyme increased) was reported for a subject receiving EA3571 in Cohort 1-7 (800 mg, Japanese) and considered unrelated to the study treatment by the investigator. Most TEAEs were considered unrelated to treatment and resolved without any action with study treatment.

There were no apparent dose- or treatment-related trends or clinically significant findings for clinical laboratory evaluations, vital signs, body weight, skeletal mass index, or 12-lead ECGs after single or multiple doses of EA3571. At single oral dosing, the plasma EA3571 concentrations increased monotonically, and after reaching the peak, plasma EA3571 concentrations declined in a monophasic manner. At doses of 800 mg and higher, plasma EA3571 concentrations no longer increased and time to peak concentrations was delayed. At single oral dosing, EA3571 was mostly excreted up to 4 hours postdose and cumulative urinary excretion rates of EA3571 reached a plateau up to 10 hours. At multiple oral dosing 3 times daily for 7 days, EA3571 was also monotonically absorbed and excreted without marked accumulation.

Single oral doses of EA3571 were well-tolerated with a favorable safety profile of up to 1200 mg in Japanese and up to 800 mg in Caucasian healthy adult males. Multiple oral doses of EA3571 were also well-tolerated with a favorable safety profile up to 200 mg 3 times daily for 7 days in Japanese and Caucasian healthy adult males. At single or multiple oral dosing, EA3571 was monotonically absorbed and excreted without marked accumulation.

Oct. 02, 2024

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2051220036

Takeuchi Yutaka

EA Pharma Co., Ltd

2-1-1, Irifune, Chuo-ku, Tokyo

contact_ea@eapharma.co.jp

Takeuchi Yutaka

EA Pharma Co., Ltd

2-1-1, Irifune, Chuo-ku, Tokyo

+81-3-6280-9600

contact_ea@eapharma.co.jp

Complete

June. 17, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. A Japanese or Caucasian healthy adult aged between 20 and 44 inclusive at the time of written informed
consent
2. A BMI meeting the following criterion at screening:
Japanese subjects, >= 18.5 and < 25.0 kg/m2
Caucasian subjects, >= 18.5 and < 30.0 kg/m2
3. Consenting in writing to participate in this clinical study on his/her own free will and able to comply with
the requirements in the clinical study

1. Surgical history at screening that affects the PK of the investigational product
2. History or complication at screening or any physical finding, vital sign, ECG finding, or laboratory value at screening or baseline that raises suspicion of a clinically abnormal symptom or organ dysfunction that requires treatment
3. History of allergy to gelatin, other foods, or any drugs at screening
4. Use of prescription drugs or over-the-counter drugs within 4 weeks before the investigational product administration
5. Ongoing participation in another clinical study, or use of an investigational product or device while participating in another clinical study within 16 weeks before giving consent
6. Anyone deemed ineligible to participate in this clinical study by the investigator or sub investigator

Male

Nonalcoholic Steatohepatitis

Single or multiple oral doses of EA3571 or placebo

Safety: AEs, Laboratory tests, Vital signs, Body weight, 12-lead ECGs, Physical findings
Pharmacokinetics: Plasma EA3571 concentrations, Urinary EA3571 excretions

June. 10, 2022

none