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Phase I clinical study for safety and pharmacokinetic evaluation of NMB58 in Japanese healthy adult male

Phase I clinical study for safety and pharmacokinetic evaluation of NMB58 in Japanese healthy adult male

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The age [mean (standard deviation), hereafter the same], height, weight, and BMI of subjects included in the safety analysis set in this study were 29 (5) years, 171.5 (5.6) cm, 66.9 (8.9) kg, 22.7 (2.2) kg/m2, respectively.

Of the 39 screened subjects, 10 subjects who received one investigational drug on day 1 and day 2 each (cohort 1 (exercise stress group): 5 subjects, cohort 2 (pharmacologic stress group): 5 subjects) were used as the safety analysis set. The pharmacokinetic (radiokinetic) analysis set and the radiation dosimetry analysis set were the same populations as the safety analysis set.

One adverse event, dysphoria was reported in cohort 1 on day 2. Because this AE was not serious and mild, and the subject recovered without any treatment, we considered this AE was not related to NMB58. There were no subjects discontinued from the study due to an AE. In addition, there were no cllinically important changes or results in clinical laboratory parameteres, vital signs, and ECGs.

Based on the results of adverse events, the tolerability and safety of NMB58 administered to Japanese healthy adult males once daily for 2 days were confirmed.

The 18F activity concentrations in the whole blood peaked immediately after administration, decreased rapidly, then gradually increased to reach a plateau, and was maintained until 480 minutes after administration. The 18F uptake in the heart wall was maintained at more than about 3% ID until 51.5 minutes after administration and more than 2.5% ID until 156 minutes after administration in all tests. Regarding the radiation dosimetry, the organ with the highest absorbed dose was the kidney on day 1 and the heart wall on day 2. The effective doses of day 1 and day 2 (cohort 1 and cohort 2) were 0.021, 0.017 and 0.021 mSv / MBq.

Regarding safety, good tolerability was confirmed. As a result of the radiation dosimetry, the absorbed dose after the administration of NMB58 was considered to have a low risk of having a deterministic effect, and the effective dose was also considered to be within an acceptable range compared to existing diagnostic radiopharmaceuticals. NMB58 is considered to have a suitable dynamics as a radiodiagnostic agent for myocardial perfusion imaging.

No

Nihon Medi-Physics Co., Ltd.

3-4-10, Shinsuna, Koto-ku, Tokyo 136-0075, Japan

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Nihon Medi-Physics Co., Ltd.

3-4-10, Shinsuna, Koto-ku, Tokyo 136-0075, Japan

+81-3-5634-7363

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completed

Jan. 18, 2019

Interventional

non-randomized, open-label

diagnostic purpose

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1.Have no history or symptoms of disease that would interfere with the evaluation the subjects, and no clinically significant deviation from normal ranges in screening tests (medical history, physical examination, ECG and clinical laboratory tests (hematology, biochemistry and urinalysis)).
2.Expected ability to perform a treadmill exercise stress testing sufficiently to achieve more than 85% of age-predicted maximum heart rate (APMHR). (For cohort 1 subjects)
3.Have a body mass index (BMI) of 18 to 28 at the time of screening.

1. Be contracting a disease or having trauma that may affect pharmacokinetics.
2. Have a history of prior allergic response to any drugs.
3. Be presence of any contraindications (absolute or relative) to exercise stress testing. (For cohort 1subjects)
4. Be presence of any contraindications to pharmacologic stress testing with adenosine or administration of aminophylline. (For cohort 2 subjects)

Male

Japanese healthy male subjects

investigational material(s)
Generic name etc : flurpiridaz (18F)
INN of investigational material : flurpiridaz (18F)
Therapeutic category code : 43- Radioactive medicines
Dosage and Administration for Investigational material : Day1: 111-167MBq, 2mL of the investigational drug is administered as an intravenous bolus injection (10 seconds) under rest conditions.
Day2: 111-167MBq, 2mL of the investigational drug is administered as an intravenous bolus injection (10 seconds) under stress conditions.

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

safety
AEs, vital signs, ECGs, clinical laboratory tests and physical examinations.

other
pharmacokinetics
To assess the radiokinetics of NMB58 in healthy subjects under rest and stress conditions.
To estimate the radiation dosimetry of NMB58 in healthy subjects under rest and stress conditions.

+81-3-5803-5612

Dec. 26, 2018