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ONO-4059-14: relative bioavailability comparative study
Open-label, randomized, 4-group 4-period cross-over, single-dose study to evaluate the relative bioavailability of the new high content formulation compared with the approved drug in Japanese healthy adult male subjects

ONO-4059 relative bioavailability comparative study

25

Japanese healthy adult males (a mean age: Group 1: 23.3 years, Group 2: 27.3 years, Group 3: 32.3 years, Group 4: 29.0 years, Overall: 28.0 years)

This study was a single-center, open-label, randomized, 4-way x 4-period crossover study to evaluate the relative bioavailability of a single oral dose of the standard formulation and the test formulation (the test formulation-1, the test formulation-2 and the test formulation-3) of ONO-4059 in fasted Japanese healthy adult males. In the 44 healthy subjects who signed informed consent, total of 25 participants were randomly assigned to Groups 1 to 4 (6 participants in each of Groups 1 to 3, and 7 participants in Group 4).

No serious adverse events or adverse events leading to death were observed. Adverse events included presyncope (Grade 3) in 1/24 (4.2%) of the standard formulation group and neutrophil count decreased (Grade 3) and urinary occult blood (Grade 1) in each 1/25 (4.0%) of the test formulation-2 group. The neutrophil count decreased and urinary occult blood were adverse events related to clinical laboratory tests. The neutrophil count decreased recovered without treatment after the drugs used in the clinical trial was discontinued, and the presyncope and urinary occult blood also recovered without treatment. Of these adverse events, the neutrophil count decreased was considered to be adverse drug reaction led to discontinuation of the drugs used in the clinical trial.

In summary statistics (mean [standard deviation], median [minimum - maximum] for Tmax only) of the pharmacokinetic parameters of ONO-4059 in plasma, the Cmax values for the standard formulation, test formulation-1, test formulation-2 and test formulation-3 (same order below) were 1440 (490), 1310 (593), 1560 (440) and 1540 (781) ng/mL, respectively. The Tmax values were 1.50 (0.500-4.00), 1.50 (0.500-6.00), 1.50 (0.500-4.00), and 1.75 (1.00-4.00) hours, and the AUClast values were 8530 (1940), 8390 (2410), 9090 (2040), and 8610 (2490) ng*h/mL, respectively. The primary endpointds of the geometric mean ratios (90% confidence interval) of Cmax and AUClast to the standard formulation were 0.85 (0.69-1.04) and 0.96 (0.89-1.04) for the test formulation-1, 1.09 (0.96-1.25) and 1.06 (0.98-1.13) for the test formulation-2, and 0.96 (0.74-1.25) and 0.99 (0.90-1.09) for the test formulation-3, respectively. The relative bioavailabilities compared to the standard formulation calculated from the geometric mean of AUClast were 96% for the test formulation-1, 106% for the test formulation-2, and 99% for the test formuation-3.

The relative bioavailabilities of the test formulations compared to the standard formulation were 96% for the test formulation-1, 106% for the test formulation-2, and 99% for the test formulation-3. Therefore, the overall exposure of each test formulation was similar to that of the standard formulation. In terms of safety, only one known advrese drug reaction of the standard formulation was observed, and no new safety concerns were observed with any of the test formulations.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2071230119

Namba Yoshinobu

Ono Pharmaceutical Co.,LTD

3 -1 -1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka

clinical_trial@ono-pharma.com

Medical Information Center

Ono Pharmaceutical Co.,LTD

3 -1 -1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka

+81-120-626-190

clinical_trial@ono-pharma.com

Complete

Feb. 28, 2024

Interventional

randomized controlled trial

open(masking not used)

active control

crossover assignment

treatment purpose

1. Healthy Japanese adult males
2. The subject is aged 18 to 45 years, inclusive, at the time of signing the informed consent form.
3. The subject has a BMI of 18.5 kg/m2 or more and less than 25.0 kg/m2 (rounded down to one decimal place) at Screening.
4. Subjects who agree to use contraceptive from the start of the study drug administration to 7 days after the last dose of the study drug
5. Subject who understands the details of the study and has given written informed consent to participate in the study.

1. Those who are receiving treatment or have a history of these in the respiratory system, cardiovascular system, psychiatric system, nervous system, gastrointestinal system, immune system, liver, kidney, hematopoietic function, endocrine function, etc. (History of malignancy within 5 years before admission)
2. The subject has a disease (Asthma, Crohn's disease, etc.) that requires systemic steroids.
3. The subject has an active infection (excluding superficial mycosis).
4. The subject has a history of serious recurrent infection or chronic infection.
5. The subject has received an antibiotic infusion or has an infection requiring hospitalization within 56 days prior to hospitalization.
6. The subject has received oral antibiotics within 14 days prior to admission.
7. The subject has a history of bacteremia caused by Staphylococcus aureus or Pseudomonas aeruginosa within 1 year prior to hospitalization.
This does not apply to patients who have received treatment and are cured.)
8. The subject had a bone and soft tissue infection within 1 year prior to admission.
9. The subject has undergone surgery (excluding biopsy) within 28 days prior to admission.
10. The subject has a history of serious infection while on immunosuppressant therapy (Grade 4 or higher according to NCI-CTCAE v5.0)

Male

Primary central nervous system lymphoma
Primary macroglobulinemia
Lymphoplasmacytic lymphoma

480mg of ONO-4059 will be oraly administered with fasted condition

- Relative bioavailability
Using the administration of the test product as the test group and the administration of the reference product as the control group, the geometric mean ratios and their 90% confidence intervals for Cmax and AUClast of ONO-4059 will be calculated and used to evaluate the relative bioavailability.

- Safety
Adverse events and adverse drug reactions, lab. test (hematology, blood chemistry, coagulation, and urinalysis), vital signs (blood pressure / pulse rate, SpO2, body temperature)
- Pharmacokinetics
Summary statistics of plasma concentration and pharmacokinetic parameters (Cmax, Tmax, AUClast, AUCinf, T1/2, CL/F, kel, MRT) will be calculated for each formulation.

+81-92-283-7701

Feb. 29, 2024

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