Evaluation of performance, safety, subject acceptance, and compliance of a disposable autoinjector for subcutaneous injections in healthy volunteers

Figures & data

Figure 1 Study Design – Each subject received a total of 24 injections in three sessions of 8 injections. With 40 subjects, a total of 960 injections were expected.

Table 1 Screening and inclusion population

Screened subjects	Included subjects	Age strata
		25–35 years	45–65 years
N = 62	N = 40	12 male 8 female Mean age (SD) 28.8 (2.8) years	8 male 12 female Mean age (SD) 54.5 (5.8) years

Notes: Nonincluded subjects, N = 22. Eight subjects removed their consent, seven subjects didn’t satisfy eligibility criteria, and seven subjects were not included because age strata was already full when the center obtained all their screening results.

Table 2 Fluid leakage and injected volume, gravimetric method (primary endpoint) – per protocol populationa

Volume	System	N	Leakage (μL)		Injected volume (μL)
			Mean (SD)	Median (MAD)e	Mean (SD)	Median (MAD)e
0.2 ml	Self-injection/subject	205	1.7 (2.4)	1.0 (1.0)	206.8 (8.0)	207 (4)
	Syringe/nurse	233	2.1 (2.6)	1.0 (1.0)	206.6 (5.8)	208 (2)
1 ml	Self-injection/subject	206	3.3 (17.5)c	1.0 (1.0)	1013.0 (19.9)	1015 (4)
	Syringe/nurse	227	1.6 (2.0)	1.0 (1.0)	1012.0 (7.1)	1013 (3)
Total of analyzed injections		871
	Missing data	1 missing value for an injection by a nurseb
		88 leakages were not collectedd
Total of performed injections		960

Notes:

a the per protocol population is the study population used for the main criteria analysis (excluding the 88 cases without leakage collection);

b one missing value for an injection into the abdomen by a health care professional;

c this mean (SD) is inflated by an outlying value of 223μL (the mean [SD] without this outlying value is 2.2 μL [8.5 μL]);

d When the leakage was not collected it was impossible to calculate the injected volume. Cases without leakage collected (n = 88) were excluded from main criteria analysis;

e Median Absolute deviation.

Figure 2 Box plots of depth of fluid depot in mm from skin surface after injection (ultrasound examination data). Description by device and volume for the per protocol population (mean, median, 25th and 75th percentiles, and range).

Note: *Statistically outlying values.

Figure 3 Perceived pain, 100 mm visual analog scale (VAS; secondary endpoint) – per protocol population.

Table 3 Perceived pain, 100 mm visual analog scale (VAS) and verbal scale (VS) – per protocol population

PP set	Device		Volume		Device				Site		Gender
	Self-injection	Injection by nurse			Self-injection		Injection by nurse
			0.2 ml	1 ml	0.2 ml	1 ml	0.2 ml	1 ml	Abdomen	Thigh	Male	Female
Na	480	480	480	480	240	240	240	240	481	479	480	480
Pain VASb:
Mean (SD)	6.6 (9.6)	15.2 (16.6)	9.2 (13.5)	12.6 (14.7)	4.6 (7.3)	8.5 (11.1)	13.8 (16.5)	16.7 (16.5)	10.6 (13.8)	11.1 (14.6)	13.1 (15.3)	8.7 (12.6)
P-valuesc	P < 0.0001		P = 0.0003		P = 0.5738 (NS)d				P = 0.6143 (NS)d		P < 0.0001
Pain VSb:
Mean (SD)	12.1 (9.8)	22.3 (14.0)	14.7 (12.1)	19.6 (13.6)	9.4 (7.8)	14.7 (10.9)	20.0 (13.4)	24.6 (14.2)	17.1 (12.9)	17.2 (13.3)	17.4 (12.2)	16.9 (14.0)
P-valuesc	P < 0.0001		P < 0.0001		P = 0.6408 (NS)d				P = 0.9034 (NS)d		P = 0.7846 (NS)d

Notes:

a no missing data;

b in mm;

c P-values from mixed model;

d NS = not statistically significant.

Table 4 Local skin reactions at injection site – Safety populationa

	Auto-injector/subject	Syringe/nurse
Bleedingb N (%)	207 (43.1)	51 (10.6)	P < 0.0001c
Edema N (%)	16 (3.3)	92 (19.2)	P < 0.0001c
Bruising N (%)	3 (0.6)	1 (0.2)	Not significantd
Itching N (%)	1 (0.2)	0 (0.0)	Not significantd
Erythema N (%)	6 (1.3)	5 (1.1)	Not significantd

Notes:

a the safety population includes all subjects with at least one injection;

b 132/207 (63.8%) for Auto-injector/Subject and 30/51 (58.8%) for Syringe/Nurse are categorized as “just a spot”;

c from ordinal logistic regression;

d Fisher’s exact test.

Figure 4 Device acceptability score for four injection scenarios (mean and 95% confidence interval).

Notes: At study end the subjects had to answer these four questions with a quotation from 1 (“Not at all probable”) to 9 (“Completely probable”): “For a further chronic treatment administered by SC injection, I agree that I will perform myself these injections with an auto-injector?”, I agree that I will perform myself these injections with a syringe?, I agree that a nurse will give me these injections with an auto-injector?, I agree that a nurse will give me these injections with a syringe?