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Investigation of safety, tolerability and pharmacokinetics of subcutaneously co-administered single doses of NNC0480-0389 and semaglutide in healthy Japanese male subjects

A research study of how the medicine NNC0480-0389 taken with semaglutide works in the body of healthy Japanese men

24

Demographics and other baseline characteristics All subjects were Asian (Japanese) males with a mean age of 37 years. The demographics and baseline characteristics were generally similar across the treatment groups.

This was a randomised, single-centre, double-blind, placebo controlled, six-armed, parallel-grouped trial investigating the safety, tolerability, and pharmacokinetics of subcutaneously co-administered single doses of NNC0480-0389 (1.7 mg, 8.6 mg or 30 mg) and semaglutide (0.5 mg only) as separate injections in healthy Japanese male subjects. Each of the three dose groups consisted of two arms (treatment arm and placebo arm) and eligible subjects were randomised to one of the six-arms (3:1:3:1:3:1). Due to differences in injection volumes, the placebos were volume-matched within each dose group and the trial was blinded within each of the three dose groups and not between the three dose groups. NUMBER OF SUBJECTS (PLANNED AND ANALYSED) A total of 24 subjects were planned to be randomised. A total of 48 subjects were screened with 24 subjects randomised and included in both FAS and SAS. All 24 randomised subjects completed the trial.

-Co-administered single doses of NNC0480-0389 s.c. and semaglutide s.c. were well-tolerated in healthy Japanese male subjects, and no safety concerns were identified. -There was no apparent correlation between dose of NNC0480-0389 and number of AEs or proportion of subjects reporting AEs. Twenty-two (22) AEs were reported in 12 subjects (66.7% (12/18)) receiving active treatment. No AEs were reported in the placebo arms. Of the 22 AEs, 19 AEs in 11 subjects were judged by the investigator as possibly or probably related to trial products. -No deaths and no SAEs were reported. -No subjects withdrew from the trial due to an AE. -All AEs were mild in severity except for one moderate AE, and none were severe. -The most frequently reported AEs were within the SOCs of Gastrointestinal disorders and Metabolism and nutrition disorders, driven by, respectively, the PT abdominal distension and decreased appetite. -One (1) subject experienced an injection site reaction judged by the investigator as unlikely related to trial product. -A trend for increase in heart rate and pulse rate was seen for subjects receiving NNC0480-0389 and semaglutide. -No other clinically significant abnormalities were reported for clinical laboratory assessments, physical examination or vital signs.

Pharmacokinetic results -Increasing NNC0480-0389 exposure (AUC0-oo and Cmax) was seen with increasing dose of NNC0480-0389 s.c. and the NNC0480-0389 exposure increased in a dose proportional manner. The estimated effect on exposure of doubling the dose (2B) was 2.02 (95% CI: 1.94, 2.11) and 2.03 (95% CI: 1.92, 2.14) for AUC0- oo,NNC0480-0389,SD and Cmax,NNC0480-0389,SD, respectively. -The geometric mean t1/2 of NNC0480-0389 ranged from 113 to 119 hours. -The median tmax ranged from 36.0 to 48.0 hours for NNC0480-0389. -Semaglutide exposures (AUC0-oo and Cmax) were not significantly affected across the three NNC0480-0389 dose levels co-administered with 0.5 mg semaglutide s.c.

-Single doses of co-administered NNC0480-0389 s.c. (up to 30 mg) and semaglutide s.c. (0.5 mg) were well-tolerated and no safety concerns were identified in healthy Japanese male subjects. -NNC0480-0389 exposure (AUC0-oo and Cmax) increased in a dose proportional manner. -The observed half-life of NNC0480-0389 was approximately 5 days. -Semaglutide exposure (AUC0-oo and Cmax) was not significantly affected across the three NNC0480-0389 levels.

June. 20, 2023

Yes

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com URL:http://novonordisk-trials.com

https://jrct.mhlw.go.jp/latest-detail/jRCT2071210021

Hashida Masahiro

Novo Nordisk Pharma Ltd.

2-1-1, Marunouchi, Chiyodaku, Tokyo

JPHC_clinical_trials@novonordisk.com

Hashida Masahiro

Novo Nordisk Pharma Ltd.

2-1-1, Marunouchi, Chiyodaku

+81-362661000

JPHC_clinical_trials@novonordisk.com

Complete

May. 18, 2021

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

-Male aged 20-55 years (both inclusive) at the time of signing the informed consent.
- Both parents of Japanese descent.
- Body mass index between 20.0 kg/m2 and 24.9 kg/m2 (both inclusive).
- Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

-Any disorder which in the investigators opinion might jeopardise subjects safety or compliance with the protocol.
- HbA1c >= 6.5% (48 mmol/mol) at screening.
- Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of acetaminophen, ibuprofen and acetylsalicylic acid, or topical medication not reaching systemic circulation within 14 days prior to the day of screening.
- Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions.

Male

type 2 diabetes

Single dose of subcutaneous NNC0480-0389 (1.7 mg, 8.6 mg or 30 mg) and semaglutide (0.5 mg only) or a single dose of subcutaneous NNC0480-0389 placebo and semaglutide placebo as separate injections
Screening visit, in-house treatment (5 nights) and follow-up visit
Follow-up period afrer dosing is 42 days.
Trial duration is 45 - 72 days for each subject (depending on time of screening relative to dosing)

Number of treatment emergent adverse events

- Area under the NNC0480-0389 plasma concentration-time curve from time 0 to infinity upon a single-dose
- Maximum plasma concentration of NNC0480-0389 upon a single-dose
- Area under the semaglutide plasma concentration-time curve from time 0 to infinity upon a single-dose
- Maximum plasma concentration of semaglutide upon a single-dose

+81-92-283-7701

April. 09, 2021

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