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CS-8958 Clinical Pharmacology study - Safety and pharmacokinetics of nebulized laninamivir octanoate (CS-8958) after a single inhaled administration in healthy male Japanese subjects -

Safety and pharmacokinetics of nebulized CS-8958

64

The mean age was 25.3, the mean body weight was 62.3 kg. No notable difference was found among the administration groups.

A total of 64 subjects who were confirmed to be eligible were enrolled after obtaining informed consent for the study. There were no subjects withdrawn from the study.

- No deaths and other serious adverse events were reported in the study. - The incidence of treatment emerged adverse events (TEAEs) was 20.0% (8/40) in the plasma pharmacokinetics (PK) study part (single inhaled administration of CS-8958 40 to 320 mg) and 45.8% (11/24) in the pulmonary PK study part (single inhaled administration of CS-8958 160 mg). Two TEAEs in the plasma PK study part were considered related to the study drug. - No clinically relevant changes from baseline were seen in laboratory parameters, vital signs, 12-lead ECG parameters, or body weight, except for the abnormal change in the laboratory values reported as TEAEs.

- After a single inhaled administration of CS-8958 40 to 320 mg, the Cmax, AUCinf an AUClast for both CS-8958 and laninamivir (the active metabolite of CS-8958) increased almost dose proportionally. - After a single inhaled administration of CS-8958 160 mg, both CS-8958 and laninamivir concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) were much higher than those in plasma and lasted for 168 h after dosing, with a longer t1/2 than that in plasma. Laninamivir concentrations in ELF and AM exceeded the 50% inhibitory concentrations for viral neuraminidase up to 168 h.

Please refer to "adverse events" section since secondary outcome measures in the study are safety.

After a single inhaled administration of CS-8958 40 to 320 mg, plasma concentrations of CS-8958 and laninamivir increased almost dose proportionally. After a single inhaled administration of CS-8958 160 mg, laninamivir was retained in the trachea and lungs over long periods, and these PK profiles support its long-lasting effect against influenza virus infection. A single administration of 40 to 320 mg of CS-8958 inhaled using a nebulizer was no safety concern and well tolerated in healthy adult subjects

Oct. 23, 2017

https://pubmed.ncbi.nlm.nih.gov/29061751/

No

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DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Aug. 31, 2015

Interventional

single-center, open labeled, single dose

other

1

1) male Japanese
2) between the age of 20 and 45
3) between the BMI of 18.5 and 25.0

1) Subjects with abnormal lung function tests will be excluded.

Male

healthy volunteers

investigational material(s)
Generic name etc : CS-8958
INN of investigational material : laninamivir
Therapeutic category code : 625 Anti-virus agents
Dosage and Administration for Investigational material : CS-8958 40 to 320 mg, single inhalation

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

pharmacokinetics
Pharmacokinetic parameters for CS-8958 and laninamivir

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Aug. 28, 2015