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DS-7830A PHASE 1 STUDY-A study to assess the safety,tolerability, and pharmacokinetics of single and multiple oral administration of DS-7830a in Japanese healthy adults, and to evaluate the effect of food (high-fat and low-fat meal) on the pharmacokinetics of orally administrated DS-7830a in Japanese healthy adults-

DS-7830A PHASE 1 STUDY-A study to assess the safety,tolerability, and pharmacokinetics of single and multiple oral administration of DS-7830a in Japanese healthy adults, and to evaluate the effect of food (high-fat and low-fat meal) on the pharmacokinetics of orally administrated DS-7830a in Japanese healthy adults-

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[Part 1] In the safety analysis set, the mean age was 27.8 years, mean body weight was 63.36 kg, mean BMI was 21.36 kg/m^2, and there were 32 males. The main demographic and other baseline characteristics of the PK analysis set were similar to those of the safety analysis set, with no notable imbalances between treatment groups. [Part 2] In the safety analysis set, the mean age was 34.4 years, mean body weight was 61.69 kg, mean BMI was 21.45 kg/m^2, and there were 18 males. The main demographic and other baseline characteristics of the PK analysis set were similar to those of the safety analysis set, with no notable imbalances between treatment groups. [Part 3] In the safety analysis set, the mean age was 30.1 years, mean body weight was 56.36 kg, and mean BMI was 20.11 kg/m^2. There were 7 males and 7 females. The main demographic and other baseline characteristics of the PK analysis set and pharmacodynamic analysis set were similar to those of the safety analysis set, with no notable imbalances between treatment groups.

[Part 1] Part 1 consisted of 4 cohorts. In each cohort, 6 participants were randomized to the DS-7830a group and 2 participants to the placebo group, and the study drug was administered as a single oral dose. All 32 participants who received the study drug completed the trial, and no participants discontinued. [Part 2] Part 2 consisted of a 6-group, 3-period crossover with three food conditions. 3 participants were randomized to each group and received DS-7830a as a single oral dose under assigned food conditions (fasting, low-fat meal, high-fat meal). All 18 participants who received the study drug completed the trial, and no participants discontinued. [Part 3] In Part 3, 5 participants of each sex were randomized to the DS-7830a group and 2 participants to the placebo group, and the study drug was administered orally once daily for 10 days under fasting conditions. All 14 participants who received the study drug completed the trial, and no participants discontinued.

-The incidence of TEAEs in Part 1 was 16.7% (4/24) in the overall DS-7830a group and 12.5% (1/8) in the placebo group. In Part 2, the incidence of TEAEs by dosing condition was 16.7% (3/18) under fasting conditions, 11.1% (2/18) under low-fat meal conditions, and 11.1% (2/18) under high-fat meal conditions. In Part 3, the incidence of TEAEs was 30.0% (3/10) in the DS-7830a group, with no TEAEs reported in the placebo group. -TEAEs reported in >=2 participants were increased C-reactive protein in the overall DS-7830a group in Part 1, increased C-reactive protein under fasting conditions in Part 2, and headache in the DS-7830a group in Part 3. -Among TEAEs in Part 1, glucose urine present (DS-7830a 10 mg group) and blood creatinine increased (DS-7830a 80 mg group) were assessed as related to the study drug. Among TEAEs in Part 2, headache, terminal insomnia, and urticaria observed in the same participant (under low-fat meal conditions) were assessed as related to the study drug. Among TEAEs in Part 3, urticaria (DS-7830a group) was assessed as related to the study drug. All were mild in severity and resolved without treatment. -No deaths, other serious adverse events, or adverse events leading to discontinuation were reported. -Apart from changes assessed as adverse events, no clinically significant changes were observed in laboratory tests, body weight, vital signs, or 12-lead ECG.

Safety Evaluation Parameters: Refer to "Adverse Events" Pharmacokinetic Evaluation Parameters: [Part 1] -Following single oral administration of DS-7830a at doses of 10 mg to 80 mg to healthy Japanese adults, the median Tmax of plasma DS-7830a ranged from 1.13 to 1.75 hours, and the geometric mean t1/2 ranged from 5.51 to 6.09 hours, remaining relatively constant regardless of dose. -Dose proportionality analysis for Cmax, AUClast, and AUCinf demonstrated dose proportionality across DS-7830a doses of 10 mg to 80 mg. [Part 2] -Compared to fasting conditions, oral administration of DS-7830a 40 mg with food condition (high-fat and low-fat meals) resulted in approximately 12-14% increase in AUC and delayed median Tmax from 1.00 to 1.50 hours, while no notable differences were observed in Cmax. [Part 3] -During multiple oral administration of DS-7830a 40 mg once daily for 10 days, steady state was achieved by at least Day 3 of study drug administration, with no notable accumulation or reduction in plasma DS-7830a concentrations, and no apparent gender differences in PK were observed. Pharmacodynamic Evaluation Parameters: [Part 3] -Evaluation of Choice Reaction Time (CRT) during multiple oral administration of DS-7830a 40 mg once daily for 10 days showed no notable changes between the DS-7830a and placebo groups at any time point.

-Single doses of DS-7830a (10-80 mg) , multiple doses (40 mg QD for 10 days) and single doses (40 mg) with food conditions showed no clinically significant safety concerns. -Single doses demonstrated dose-proportional exposure. -Compared to fasting conditions, single doses with food conditions resulted in 12-14% increase in AUC and delayed Tmax by 0.5 hours. -In multiple dose part, steady state was achieved with no notable accumulation or reduction in plasma DS-7830a concentrations.

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https://jrct.mhlw.go.jp/latest-detail/jRCT2051230152

Inoguchi Akihiro

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

Daiichi Sankyo Co., Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Complete

Dec. 26, 2023

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Healthy Japanese adults
2. Age: 18 to 45 years at the time of informed consent
3. Body mass index (BMI) at screening: >=18.5 and <25.0 kg/m^2

Exclusion criteria at screening
1. Having a history of a serious disease attributable to central nervous, psychiatric, cardiovascular, respiratory, blood and hematopoietic, or gastrointestinal system disorders, or other disorders including hepatic/renal impairment, thyroid dysfunction, pituitary malfunction, and adrenal insufficiency, and the conduct of the study is not appropriate for the safety of the subject as judged by the investigator or subinvestigator.
2. Having clinically significant symptoms (eg, headache, dizziness), findings (eg, blood pressure decreased), abnormalities on ECG, or deviations from the reference ranges for laboratory tests at the study site at screening as judged by the investigator or subinvestigator (however, the subject will not be excluded if the disease will not affect participation in the study as judged by the investigator or subinvestigator).
3. Having a history of hypersensitivity to any drugs or substances, or being idiosyncratic (eg, having penicillin allergy).
4. Having alcohol or drug dependence.
5. Having received or planning to receive treatment by other physicians during the period from 14 days before study drug administration to the post-study examination or the follow-up examination.
etc

Both

major depressive disorder

10 to 80 mg of DS-7830a or Placebo is administered at a single oral dose, or an appropriate dose of DS-7830a within the dose range as stated above or Placebo is administered at multiple oral doses.

Safety: Adverse events (AEs), laboratory data, body weight, vital signs, standard 12-lead electrocardiogram(ECG), Holter ECG and Columbia-Suicide Severity Rating Scale (hereinafter referred to as C-SSRS).
Pharmacokinetics: Pharmacokinetic parameters of plasma and urine DS-7830a concentrations

Safety: AEs, laboratory data, body weight, vital signs, standard 12-lead ECG, and C-SSRS.
Pharmacodynamics: Choice Reaction Time (CRT) task

+81-6-6395-9000

Dec. 21, 2023

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