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A Phase 1, Single-center, Parallel-group, Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of EB-1020 in Healthy Adult Male Subjects

A Phase 1 Clinical Trial of EB-1020 in Healthy Subjects (Single and Multiple Ascending Doses)

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In Part A, the 24 subjects in the EB-1020 groups had a mean age of 21.3 years (range: 18 to 30 years), with a mean BMI of 21.54 kg/m2 (range: 19.1 to 24.3 kg/m2). Of the 9 subjects in the placebo group, there was a mean age of 22.1 years (range:18 to 28 years), with a mean BMI of 20.42 kg/m2 (range: 19.0 to 22.5 kg/m2). In Part B, the 16 subjects in the EB-1020 groups had a mean age of 25.9 years (range: 18 to 36 years), with a mean BMI of 22.91 kg/m2 (range: 21.2 to 24.8 kg/m2). Of the 6 subjects in the placebo group, there was a mean age of 22.7 years (range: 19 to 27 years), with a mean BMI of 22.42 kg/m2 (range: 20.4 to 23.5 kg/m2).

A total of 33 subjects were randomized and administered the IMP in Part A of the trial (24 subjects in the EB-1020 groups and 9 subjects in the placebo group). All 33 subjects were analyzed for safety and all 24 subjects in the EB-1020 groups were analyzed for PK. All 33 subjects in Part A completed the trial. A total of 22 subjects were randomized and administered the IMP in Part B of the trial (16 subjects in the EB-1020 groups and 6 subjects in the placebo group). All 22 subjects were analyzed for safety and all 16 subjects in the EB-1020 groups were analyzed for PK. All 22 subjects in Part B completed the trial.

Part A: - None of the 24 subjects who received a single oral dose of EB-1020 QD XR capsule (82.2 mg, 164.4 mg, or 328.8 mg) experienced TEAEs during the trial. - None of the 9 subjects who received placebo experienced TEAEs during the trial. Part B: - None of the 16 subjects who received a QD oral dose of EB-1020 QD XR capsule (164.4 mg or 328.8 mg) for 5 days experienced TEAEs during the trial. - None of the 6 subjects who received placebo experienced TEAEs during the trial.

Part A: - Mean Cmax, AUCInfinity and AUCt of EB-1020 increased in a dose-dependent manner for the dose range of 82.2 to 328.8 mg. - For EB-1020, following single administration for the dose range of 82.2 to 328.8 mg, the 95% CIs for the slopes of Cmax (1.11 to 1.36) and AUCInfinity (1.02 to 1.33) did not include 1. The slopes of Cmax and AUCInfinity were slightly higher than 1 at 1.23 and 1.17, respectively. - For EB-1020, median tmax ranged from 5.00 to 6.00 hours and mean t1/2,z ranged from 3.1 to 7.1 hours. - Mean CL/F of EB-1020 ranged from 20.5 to 25.9 L/h. Part B: - Following multiple oral administrations of EB-1020 QD XR capsule once daily for 5 days, EB-1020 plasma concentration reached a steady state by Day 4. - Mean Cmax and AUC24h of EB-1020 on Day 1 and Day 5 increased in a dose-dependent manner for the dose range of 164.4 to 328.8 mg. - For EB-1020, median tmax ranged from 5.50 to 7.00 hours on Day 1 and 3.00 to 3.50 hours on Day 5. Mean t1/2,z ranged from 2.8 to 4.2 hours on Day 5. Mean CL/F ranged from 18.1 to 18.8 L/h on Day 5. - Mean accumulation ratios of Day 5 to Day 1 for Cmax, AUC24h and Ctrough ranged from 1.16 to 1.39, 1.16 to 1.17, and 0.594 to 0.825, respectively, indicating minimal accumulation of EB-1020 following multiple QD administrations. - EB-1020 QD XR capsules administered as single oral doses at 82.2 to 328.8 mg and EB-1020 QD XR capsules administered as multiple oral doses at 164.4 to 328.8 mg were safe and well tolerated in healthy adult male subjects.

- Following single and multiple oral administrations of EB-1020 QD XR capsule, the mean Cmax, AUCInfinity and AUCt of EB-1020 increased in a dose-dependent manner. - Following multiple oral administrations of EB-1020 QD XR capsule for 5 days, minimal accumulation of EB-1020 was observed. - EB-1020 QD XR capsules administered as single oral doses at 82.2 to 328.8mg and EB-1020 QD XR capsules administered as multiple oral doses at 164.4 to 328.8mg were safe and well tolerated in healthy adult male subjects.

Yes

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Supporting Materials: Study Protocol and Statistical Analysis Plan (SAP) Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data. Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.

https://jrct.mhlw.go.jp/latest-detail/jRCT2071220029

Sanada Nobuhito

Otsuka Pharmaceutical Co., Ltd.

3-2-27, Otedori, Chuo-ku, Osaka-shi

G_CL_EB-1020_P1@otsuka.jp

Drug Information Center

Otsuka Pharmaceutical Co., LTD.

2-16-4, Konan, Minato-ku, Tokyo, Japan

+81-3-6361-7314

opc_ctr@otsuka.jp

Complete

July. 15, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1) Japanese males age 18 years or older and younger than 40 years at the time of informed consent
2) Body mass index (BMI = body weight(kg)/(height{m})2) of>=19.0kg/m2 and=<25.0kg/m2 at screening
3) Body weight of>=50kg at screening
4) Subjects who are capable of providing their own signed informed consent prior to the start of any trial-related procedure and who are judged by the investigator or subinvestigator to be capable of meeting all of the requirements of the trial

1) Subjects who, on the basis of their medical history or the physical examination at either screening or admission, are judged by the investigator or subinvestigator to be placed at risk or to have a clinically significant abnormality that might possibly affect the evaluation endpoints, including drug absorption, distribution, metabolism, or excretion
This may include, but is not limited to, a medical history or complication of cardiac, hepatic, renal, neurologic, endocrine, gastrointestinal, respiratory, hematologic, or immunologic disease.
2) Subjects with systolic blood pressure of >140mmHg or <100mmHg or diastolic blood pressure of >90mmHg or <50mmHg after at least 3 minutes rest in the supine, sitting, or standing position (at either screening or admission), or with orthostatic blood pressure decrease (systolic blood pressure in supine position minus systolic blood pressure in standing position) of >=20mmHg(at screening)
3) Subjects whose pulse rate in the supine position after resting for at least 3 minutes is not within the range of 50 to 90bpm(at either screening or admission)
4) Subjects who have a medical history or current symptoms of hepatitis or acquired immunodeficiency syndrome
5) Subjects with a positive result in immunological tests (hepatitis B surface antigen[HBsAg], hepatitis C virus(HCV)antibody, human immunodeficiency virus[HIV] antigen and antibody, syphilis) or polymerase chain reaction (PCR) test (SARS-CoV-2) at screening
6) Subjects with a history of drug allergy
7) Subjects with a positive result in alcohol breath test or urine drug test at screening or admission (positive result for alcohol breath test: concentration of >0.00 mg/L)

Male

Attention deficit hyperactivity disorder (ADHD)

[Part A]
Subjects will receive single oral administration of EB-1020 once-daily extended-release(QD XR) capsule(82.2,164.4,or 328.8mg) or placebo capsule.
[Part B]
Subjects will receive 5-day repeated oral administration of EB-1020 QD XR capsule(164.4 or 328.8mg/day) or placebo capsule.

Safety endpoints
-Adverse events (AEs)
-Clinical laboratory tests (hematology, blood chemistry, urinalysis)
-Physical examination
-Neurological examination
-Vital signs (blood pressure, pulse rate, body temperature, respiratory rate)
-Body weight
-12-Lead electrocardiogram (ECG)
-Columbia-Suicide Severity Rating Scale (C-SSRS)
Pharmacokinetic endpoints
-Plasma concentrations of EB-1020 and EB-10601
-Pharmacokinetic parameters of EB-1020 and EB-10601
-Cumulative parameters of EB-1020 and EB-10601
-AUC ratio for EB-10601 to EB-1020
-Dose proportionality of Cmax and AUC of EB-1020 and EB-10601

+81-92-283-7701

July. 08, 2022

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