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A randomized, placebo-controlled, single-blind, dose escalation study to investigate the safety, tolerability, and pharmacokinetics of BAY 2395840 after single and multiple dose in Japanese healthy male participants

Phase 1 study of BAY 2395840 in Japanese healthy male participants

36

All 36 treated participants were included in the safety analysis set (SAF). 26 participants treated with BAY 2395840 were included in the PK analysis set (PKS). The 10 participants treated with placebo were not included in the PKS. All 36 participants (100.0%) of the SAF were male and Asian without Hispanic or Latino ethnicity. The participants had a mean age of 27.4 years (range: 20 to 45 years).

In total, 110 healthy male participants were enrolled into this study. 74 participants were screening failures and 36 participants were randomized. In Dose steps 1 to 3, 6 participants were randomized to active treatment and 2 participants to placebo per dose step. In Dose step 4, 8 participants were randomized to active treatment and 4 participants to placebo. All 36 randomized participants were treated and completed the study as well as the follow-up phase.

No deaths or other treatment-emergent serious adverse events were reported during this study. None of the 36 treated participants had a TEAE that led to discontinuation of study intervention. The TEAEs were of mild intensity in 2 participants (5.6%) and of moderate intensity in 1 participant (2.8%). All TEAEs were reported as resolved at the end of the study and considered by the investigator as not related to the study intervention.

Primary variable: TEAEs were reported by 3 participants (8.3%). The TEAEs included (by preferred term [PT]) blood creatine phosphokinase increased after an SD of placebo, medical device site dermatitis after an SD of the 2nd dose level BAY2395840, and alanine aminotransferase (ALT) increased after MDs of the 3rd dose level BAY2395840 (ALT increased to a maximum of 1.64 times upper limit of normal (ULN) and was in the normal range at the FU). Laboratory parameter changes reported as TEAEs (blood creatine phosphokinase increased, and alanine aminotransferase increased) were considered as not related to study intervention administration and were resolved at latest by the end of the study. No clinically relevant changes of vital signs and ECG parameters occurred. Secondary variables: The geometric means of Cmax (maximum observed drug concentration in measured matrix after single dose administration) of BAY2395840 at dose levels 1, 2, and 3 were 19.4, 46.8, and 75.0 mg/L, respectively. The geometric means of AUC (area under the concentration vs. time curve from zero to infinity after single (first) dose) at dose levels 1, 2, and 3 were 210, 418, and 757 mg h/L, respectively. The geometric means of AUC(0-24) (AUC from time 0 to 24 h after single dosing) at dose levels 1, 2, and 3 were 156, 330, and 587 mg h/L, respectively. In Dose step 4, the geometric means of Cmax,md (Cmax after MD administration during a dosage interval, directly taken from analytical data) and AUC(0-24)md (AUC from time 0 to 24 h after multiple dosing) of BAY2395840 were 71.8 mg/L and 711 mg h/L, respectively.

- BAY2395840 was safe and well tolerated at tested dose in Japanese healthy male participants. - Dose-normalized parameters (AUC/D and Cmax/D) were comparable for the 3 dose strengths which indicates dose-proportionality. - After daily dosing of the 3rd dose level BAY2395840 for 7 days, the mean accumulation ratio for AUC(0-24) and Cmax was 1.31 and 1.08, respectively. Thus overall, slight accumulation in plasma was observed after multiple administrations.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071220060

Myoishi Masafumi

Bayer Yakuhin, Ltd.

2-4-9 Umeda, Kita-ku, Osaka, Osaka

byl_ct_contact@bayer.com

Dedicated contact

Bayer Yakuhin, Ltd.

2-4-9 Umeda, Kita-ku, Osaka, Osaka

+81-6-6133-6363

byl_ct_contact@bayer.com

Complete

Oct. 07, 2022

Interventional

randomized controlled trial

single blind

placebo control

parallel assignment

other

- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs (BP and pulse rate), 12-lead ECG, and laboratory tests. Re-screening will be allowed.
- Ethnicity: Japanese
- Participant must be 20 to 45 years of age inclusive, at the time of signing the informed consent.
- BMI above or equal 18.0 kg/m^2 and below or equal 29.9 kg/m^2 at screening
- Male
- Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Study participants of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period between signing of the ICF and 90 days after administration of the study intervention. Acceptable methods of contraception include, but are not limited to: (i) condoms (male or female); (ii) intra-uterine device; (iii) hormone-based contraception. Study participants of reproductive potential must agree to utilize 2 reliable and acceptable methods of contraception simultaneously including condoms.
- A sexually active man who has not been surgically sterilized has to agree not to act as sperm donor for the time period between signing of the ICF and 90 days after the last administration of study intervention.

- Any findings from the medical examination (including medical history, physical examination, vital signs, laboratory tests, and 12-lead ECG) deviating from normal and deemed to be of clinical relevance by the investigator.
- Relevant diseases within the last 4 weeks prior to first administration of study intervention.
- Known severe allergies.
- Regular use of therapeutic or recreational drugs.
- Suspicion of drug or alcohol abuse.
- Positive cotinine test.
- Donation of more than 200 mL of blood within 4 weeks before first administration of study intervention, donation of more than 400 mL of blood within 3 months before first administration of study intervention, or plasmapheresis within 3 months prior to first administration of study intervention.
- Intake of foods or beverages containing grapefruit, pomelo, tangelo, or Seville oranges from 7 days before first administration of the study intervention up to the last time point of PK sampling after the last administration of the study intervention.
- Special diets preventing the participants from eating the standard meals during the study conduct.
- Participation in a clinical study of an investigational drug within 4 months or of an approved drug within 3 months before the first administration of study intervention.
- Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the participants safety.
- Participant is in custody by order of an authority or a court of law.
- Participant is an employee of the sponsor or of a CRO conducting the study, or has a close affiliation with the investigational site.
- Unable/unwilling to comply with study restrictions

Male

Diabetic neuropathic pain

- Dose step 1: Each participant will receive an single dose (SD) of dose 1 of
BAY2395840 or matching placebo.
- Dose step 2: Each participant will receive an single dose (SD) of dose 2 of
BAY2395840 or matching placebo.
- Dose step 3: Each participant will receive an single dose (SD) of dose 3 of
BAY2395840 or matching placebo.
- Dose step 4:Each participant will receive multiple doses (MDs) of dose 3 of BAY2395840 or matching placebo.

Incidence of treatment emergent adverse events (TEAEs) [ Time Frame: 10 to 14 days after last administration of study intervention ]

- Cmax (maximum observed drug concentration in measured matrix after single dose administration) of BAY2395840 [ Time Frame: On day 1]
- AUC (area under the concentration vs. time curve from zero to infinity after single (first) dose) of BAY2395840 [ Time Frame: On day 1]
- AUC(0-24) (AUC from time 0 to 24 h after single dosing) of BAY2395840 [ Time Frame: On day 1]
- Cmax,md (Cmax after MD administration during a dosage interval, directly taken from analytical data) of BAY2395840 (only for Dose step 4) [ Time Frame: On day 7 ]
- AUC(0-24)md (AUC from time 0 to 24 h after multiple dosing) of BAY2395840 (only for Dose step 4) [ Time Frame: On day 7]

+81-92-283-7701

Oct. 06, 2022

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