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Randomized, placebo-controlled, single-blind, dose escalation study to investigate the safety, tolerability, and pharmacokinetics after single and multiple nasal doses of BAY 2586116 in Japanese healthy male participants (Phase 1 study of BAY 2586116 in Japanese healthy male participants)

Phase 1 study of BAY 2586116 in Japanese healthy male participants (Phase 1 study of BAY 2586116 in Japanese healthy male participants)

36

All 36 randomized participants were treated and completed the treatment, the study as well as the follow-up visit. The 36 treated participants were included in the safety analysis set (SAF). 27 participants treated with BAY2586116 were included in the PK analysis set (PKS), whereas the 9 participants treated with placebo were not included. All 36 participants (100.0%) of the SAF were male and Asian without Hispanic or Latino ethnicity. The participants had a mean age 25.6 years (range: 20 to 43 years) and a mean BMI of 21.32 kg/m2 (range: 18.3 to 26.6 kg/m2).

In total, 116 healthy male participants were enrolled into this study. 80 participants were screening failures and 36 participants were randomized. 9 participants each were randomly allocated to active treatment of lower, middle or higher dose BAY2586116 and 9 participants to placebo.

None of the 36 treated participants had a TEAE or non-treatment- emergent AE.

Primary variable: The nasal administration of BAY2586116 as SDs, or MD (OD for 5 consecutive days) was safe and systemically and locally well tolerated in this study. No deaths were reported during this study. None of the 36 treated participants had a TEAE or non-treatment- emergent AE. No clinically relevant changes of laboratory parameters, vital signs, ECG parameters, heart rate over 1 minute, respiratory rate, and oxygen saturation occurred. Secondary variables: BAY2586116 was well absorbed after nasal administration of single and multiple doses in all 3 dose groups. The geometric mean Cmax and AUC of BAY2586116 increased in a dose-dependent way following SD administration across the studied dose range of lower to higher. However, AUC and Cmax appeared to increase less than dose- proportional after administration of higher dose when compared to the preceding dose steps. The geometric mean accumulation ratios (RAAUC and RACmax) of BAY2586116 were close to 1, indicating no accumulation of BAY2586116 after multiple OD administration of higher dose for 5 consecutive days.

- The nasal administration of BAY2586116 as SDs, or MD (OD for 5 consecutive days) was safe and systemically and locally well tolerated in Japanese healthy male participants. - BAY2586116 was well absorbed after nasal administration of single and multiple doses.

Jan. 12, 2024

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071210020

Myoishi Masashi

Bayer Yakuhin, Ltd.

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

byl_ct_contact@bayer.com

contact Dedicated

Bayer Yakuhin, Ltd.

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

+81-6-6133-6363

byl_ct_contact@bayer.com

Complete

May. 10, 2021

Interventional

randomized controlled trial

single blind

placebo control

parallel assignment

other

- Participants who are overtly healthy as determined by medical evaluation (including medical and surgical history, physical examination, laboratory tests, ECG, vital signs).
- Participant must be 20 to 45 years of age inclusive, at the time of signing the ICF.
- BMI above or equal 18.0 and below or equal 29.9 kg/m2 at screening.
- Male.
- Japanese.
- Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- 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.

- A history of relevant diseases of vital organs, of the CNS (central nervous system) or other organs.
- Pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study intervention will not be normal.
- Given the nasal administration route, these diseases include (but are not limited to) any symptomatic and/or a history of relevant diseases of the ear, nose, and throat area (e.g. acute allergic rhinitis, acute infectious rhinitis, acute or chronical sinusitis, infection of the upper respiratory tract, symptomatic deviation of the nasal septum or a different relevant impairment of nasal breathing, history of any surgery of the ear, nose, and throat area [exception: sole history of adenectomy and/or tonsillectomy and/or paracentesis >1 year prior to 1st administration of study intervention], anatomical abnormalities of the ear, nose, and throat area [e.g. surgical corrected or uncorrected cheilognathopalatoschisis]).
- Liver insufficiency or active liver disease, which may include unexplained persistent transaminase elevations.
- Known or suspected liver disorders (e.g. Morbus Gilbert/Meulengracht) and bile secretion/flow (cholestasis, also history of it).
- Participants with thyroid disorders as evidenced by assessment of thyroid stimulating hormone levels outside the normal reference range at screening.
- Personal or familial history of genetically muscular diseases.
- History of autoimmune disease.
- Known hypersensitivity to the study interventions (active substances or excipients of the preparations).
- Known severe allergies, e.g. allergies to more than 3 allergens, allergies affecting the lower respiratory tract, allergic asthma, allergies requiring therapy with corticosteroids, urticarial, or significant non-allergic drug reactions.
- History of known or suspected malignant tumors.
- Tendency for vasovagal reactions (e.g. after venipuncture) or history of syncope.

Male

Obstructive sleep apnea Drug

Experimental: BAY2586116 Dose step 1 and Placebo
Each participant of Dose step 1 will receive a single dose of BAY2586116 or placebo.
In this dose step, 12 participants will be included (9 on active treatment, 3 on placebo).
Experimental: BAY2586116 Dose step 2 and Placebo
Each participant of Dose step 2 will receive a single dose of BAY2586116 or placebo.
In this dose step, 12 participants will be included (9 on active treatment, 3 on placebo).
Experimental: BAY2586116 Dose step 3 and Placebo
Each participant of Dose step 3 will receive single and multiple doses of BAY2586116 or placebo administered once daily (OD) for 5 consecutive days.
In this dose step, 12 participants will be included (9 on active treatment, 3 on placebo).

The main aim of this study is to learn more about how safe BAY2586116 is compared to the placebo. To answer this question, the researchers will count the number of participants who have medical problems that may or may not be related to the study treatment. These medical problems are also known as adverse events while they are in the study. Number of participants with adverse events [ Time Frame: From first administration up to 8 days after last dose (follow-up visit) ]

Cmax of BAY2586116 ( Time Frame: Day 1 )
Cmax: maximum observed drug concentration in measured matrix after single dose administration.
Cmax/D of BAY2586116 ( Time Frame: Day 1 )
Cmax/d: Cmax divided by dose.
AUC of BAY2586116 ( Time Frame: Day 1 )
AUC: area under the concentration vs. time curve from zero to infinity after single (first) dose.
AUC/D of BAY2586116 ( Time Frame: Day 1 )
AUC/D: AUC divided by dose.
Cmax,md of BAY2586116 ( Time Frame: Day 5 )
Only for Dose step 3.
Cmax,md/D of BAY2586116 ( Time Frame: Day 5 )
Only for Dose step 3.
AUCT,md of BAY2586116 ( Time Frame: Day 5 )
Only for Dose step 3.
AUCT,md: AUC during any planned dose interval after multiple dose.
AUCT,md/D of BAY2586116 ( Time Frame: Day 5 )
Only for Dose step 3.
AUCT,md/D: AUCT,md divided by dose.

+81-92-283-7701

May. 07, 2021

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