臨床研究等提出・公開システム

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24

Of the 24 subjects exposed to treatment in the trial, 14 were male (58.3%) and 10 were female (41.7%) with a mean age of 38.3 years. The mean body weight was 62.65 kg and mean BMI was 22.65 kg/m2. At baseline, the mean duration of diabetes was 13.0 years and mean HbA1c was 7.7%.

A total of 29 subjects were screened, of which 24 subjects were randomised and exposed to both the trial products. All 24 randomised subjects completed the trial.

In this open-label trial in Japanese subjects with T1D receiving 8 weeks of insulin 287 and 2 weeks of IGlar U100, insulin 287 was well-tolerated, no new safety issues and severe hypoglycaemic episodes were identified. <Adverse events> -A total of 18 AEs (in 13 subjects) were reported, of which 16 (in 11 subjects) were reported in insulin 287 and 2 (in 2 subjects) in the IGlar U100 treatment period. -The most commonly reported AEs in the insulin 287 treatment period were ‘nasopharyngitis’ (3 events in 2 subjects) and ‘vessel puncture site pain’ (2 events in 2 subjects). -The 2 AEs reported in the IGlar U100 treatment period were ‘conjunctivitis’ and ‘vessel puncture site pain’ (1 event in 1 subject each). -All the AEs reported in both treatment periods were mild in severity except for 1 event of ‘vomiting’ reported in the insulin 287 treatment period, which was considered to be moderate. -One (1) subject experienced an ‘injection site reaction’ in the insulin 287 treatment period and this event was possibly related to insulin 287. -All other AEs reported in both treatment periods were unlikely related to the trial product. -All the AEs were reported to be recovered or resolving at the end of treatment. -No deaths, serious or severe adverse events were reported during the trial. <Hypoglycaemic events> -No severe hypoglycaemic episodes (level 3) were reported during the treatment period. -During the treatment period, the rate of clinically significant hypoglycaemic episodes (level 2) was 3728.1 and 3060.4 episodes per 100 years of exposure for insulin 287 and IGlar U100, respectively. -During the treatment period, the rate of clinically significant nocturnal hypoglycaemic episodes (level 2) was 784.9 and 941.7 episodes per 100 years of exposure for insulin 287 and IGlar U100, respectively. <Hyperglycaemic events> -During the treatment period, the rate of hyperglycaemic episodes was 3363.7 and 3649.0 episodes per 100 years of exposure for insulin 287 and IGlar U100, respectively. <Antibodies> Nine (9, 37.5%) of the 24 subjects had pre-existing antibodies binding to insulin 287 (pre-existing antibodies are expected in subjects previously treated with insulin). -Six (6) of the remaining 15 subjects developed antibodies binding to insulin 287 during the trial. -All the subjects who were positive for antibodies binding to insulin 287 had cross-reactive antibodies to human insulin. -The median change in antibody titre from pre-insulin 287 dose to follow-up was 63.0. <Other safety assessments> -In majority of the subjects, no clinically significant vital signs and physical examination abnormalities were reported in the trial. No clinically significant abnormalities were reported for clinical laboratory or ECG assessments.

-Insulin 287 exposure was well-distributed across the one-week dosing interval at steady state with a peak around 16 hours followed by a slow decline. -F21The total exposure of insulin 287 increased with increasing dose at steady state.

Pharmacokinetic results for insulin 287 at steady state and after first dose -In a post hoc analysis for dose proportionality for insulin 287 for AUCI287,T,SS (estimated slope 1.17 [0.99; 1.36]95% CI, p=0.0650), the slope of AUC was not significantly different from 1. -The maximum concentration of insulin 287 increased with increasing dose at steady state. -In the post hoc analysis of dose proportionality for insulin 287 for Cmax,I287,T,SS (estimated slope 1.19 [0.93; 1.45]95%CI, p=0.1469), the slope of Cmax was not significantly different from 1. -Overall, the data is considered to support dose proportionality. -The median tmax,I287,SS was 16 hours with a range of 12 to 18 hours. -The t1/2 for insulin 287 after 8 weeks of dosing (geometric mean) was 164 hours with a range of 122 to 213 hours. -Steady state was reached within 3-4 weeks of once weekly administration of insulin 287. -The ratios between total exposure and Cmax at steady state and during the first week dosing interval for insulin 287 were 1.76 and 1.73, respectively. Pharmacodynamics results for insulin 287 at steady state -The duration of the glucose-lowering effect of insulin 287 covered one week at clinically relevant doses. -The fluctuation in glucose-lowering effect could be due to diurnal variation in insulin sensitivity.

The following conclusions were made based on this randomised, single-centre, open-label, 2-period cross over, multiple-dose trial investigating the steady state PK and PD properties and safety of s.c. insulin 287 administered OW (treatment for 8 weeks) and s.c. IGlar U100 administered OD (treatment for 2 weeks) in Japanese subjects with T1D. -Insulin 287 exposure was well-distributed across one week and half-life supports a OW administration. -The duration of the glucose-lowering effect of insulin 287 cover

Yes

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

Novo Nordisk Pharma Ltd.

Meiji Yasuda Seimei Bldg., 2-1-1, Marunouchi, Chiyoda-ku, Tokyo

JPHC_clinical_trials@novonordisk.com

Novo Nordisk Pharma Ltd.

Meiji Yasuda Seimei Bldg., 2-1-1, Marunouchi, Chiyoda-ku, Tokyo

+81-3-6266-1000

JPHC_clinical_trials@novonordisk.com

completed

Dec. 07, 2018

Interventional

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treatment purpose

1

Both

investigational material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : 249 Other hormone preparations (including antihormone preparations)
Dosage and Administration for Investigational material : -

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code : 249 Other hormone preparations (including antihormone preparations)
Dosage and Administration for Investigational material : -

pharmacokinetics

safety
pharmacokinetics
pharmacodynamics
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Nov. 16, 2018