臨床研究等提出・公開システム

A Phase 1, Open-Label, Randomized, Three-Period, Crossover Study to Evaluate the Relative Bioavailability of Naldemedine Granule to Tablet and the Effect of Food on the Pharmacokinetics of Naldemedine in Healthy Adult Subjects

A Phase 1, Open-Label, Randomized, Three-Period, Crossover Study to Evaluate the Relative Bioavailability of Naldemedine Granule to Tablet and the Effect of Food on the Pharmacokinetics of Naldemedine

18

In the 18 subjects receiving 1 g of naldemedine 0.02% granules and 1 naldemedine 0.2-mg tablet in a fasted state, the mean value (SD) of age, weight, BMI were 32.9 (7.0) years, 70.36 (9.35) kg, 23.23 (2.52) kg/m2, respectively. In the 17 subjects receiving 1 g of naldemedine 0.02% granules in a fed state, the mean value (SD) of age, weight, and BMI were 32.8 (7.2) years, 69.39 (8.66) kg, and 23.06 (2.49) kg/m2, respectively.

A total of 18 subjects were enrolled in the study. Of those subjects, 17 subjects completed the study. One subject discontinued the study because of withdrawal by subject.

-A total of 2 TEAEs (diarrhoea and contusion) were reported during the study in 2 subjects receiving 1 g of naldemedine 0.02% granules in a fed state. Neither event was treatment-related. No TEAEs were reported in subjects receiving 1 g of naldemedine 0.02% granules in a fasted state or 1 naldemedine 0.2-mg tablet in a fasted state. -No deaths, serious AEs, or TEAEs leading to study drug discontinuation were reported during the study.

-The Cmax, AUC0-last, and AUC0-inf of naldemedine following the administration of 1 g naldemedine 0.02% granules were slightly lower than those following the administration of naldemedine 0.2-mg tablet in a fasted state. The AUC0-last and AUC0-inf of naldemedine met the bioequivalence criteria (90% CI of 80% to 125%), while Cmax did not. -The median Tmax of naldemedine was 0.75 hours for both formulations. -Food intake decreased the mean Cmax of naldemedine by 43% when naldemedine granules were administered following a high-calorie and high-fat meal, while it did not affect AUC0-last and AUC0-inf of naldemedine. -The median Tmax of naldemedine following the administration of naldemedine granules was delayed from 0.75 hours in a fasted state to 4.00 hours in a fed stated.

See above "adverse events"

There is no significant difference in the PK of naldemedine between following the administration of naldemedine 0.02% granules and naldemedine 0.2-mg tablet in a fasted state. Regarding naldemedine 0.02%granule, food intake decreased the mean Cmax of naldemedine by 43%, while it did not affect AUC0-last and AUC0-inf of naldemedine. The median Tmax of naldemedine was delayed from 0.75 hours in a fasted state to 4.00 hours in a fed stated. There is no concern about safety and tolerability.

No

https://www.clinicaltrials.jp/file/IOkrTzOYc

Shionogi & Co., Ltd.

shionogiclintrials-admin@shionogi.co.jp

Shionogi & Co., Ltd.

+81-6-6209-7885

shionogiclintrials-admin@shionogi.co.jp

completed

April. 23, 2019

Interventional

Crossover and open-label study

treatment purpose

1

Healthy Caucasian adult subjects between the ages >=20 and <=55

Subjects who are considered by the investigator or subinvestigator to be unsuitable for participation in the study for any reason.
etc.

Both

Healthy Caucasian adult subjects

investigational material(s)
Generic name etc : naldemedine
INN of investigational material : naldemedine
Therapeutic category code : 239 Other agents affecting digestive organs
Dosage and Administration for Investigational material : Oral

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

pharmacokinetics
maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), area under the concentration-time curve extrapolated from time zero to infinity (AUC0-inf), terminal elimination rate constant (lambdaz) , terminal elimination half-life (t1/2,z), mean residence time (MRT), and apparent total clearance (CL/F).

safety
Vital signs, electrocardiograms, clinical laboratory tests, and adverse events (AEs).

April. 12, 2019