Evaluation of pharmacokinetics, user handling, and tolerability of peginterferon alfa-2a (40 kDa) delivered via a disposable autoinjector device

Figures & data

Table 1 Questions for the (A) injection-method observational survey and (B) subjective patient assessment of injection method

A Injection method observational survey*

Did the patient…

Exhibit any nervousness prior to the injection? Exhibit any difficulty initiating the injection? Appear confident performing the injection? Follow the instructions for performing the injection without the need for additional instructions or guidance? Experience any technical problems with the device or syringe during the injection? Withdraw the device/syringe before the injection was complete, as evidenced by withdrawal before the second audible click for the autoinjector, and remaining fluid in the barrel for the prefilled syringe? Exhibit any visible pain or physical discomfort (eg, hand discomfort, pain upon injection) during the injection? Appear to be satisfied using the device or syringe? Exhibit any frustration using the syringe or device?

B Patient subjective assessment of injection method Did you have any concerns about using the device before starting the injection? How comfortable were you using the device? Were the instructions easy to follow? Were there any problems with the device itself? Were there any problems performing the injection? Did you experience any pain or discomfort? Is there anything else you would like to add?

* Note: Answers recorded as “yes” or “no”.

Table 2 Demographic data for trials 1 and 2

	Trial 1 (healthy subjects) n = 50	Trial 2 (chronic hepatitis C patients)
		AI weeks 1–3; PFS weeks 4–6 n = 30	PFS weeks 1–3; AI weeks 4–6 n = 30
Male, n (%)	47 (94)	17 (57)	14 (47)
Mean age, years (range)	39.0 (13.6)	47.6 (23–74)	51.3 (27–69)
Race, n (%)
White caucasian	47 (94)	26 (87)	28 (93)
Black/African	2 (4)	4 (13)	2 (7)
Asian	1 (2)	0	0
Hispanic/latino ethnicity, n (%)	N/A	7 (23)	4 (13)
Mean body weight, kg (SD)	77.1 (9.9)	88.1 (23.2)	83.4 (17.4)
Mean BMI, kg/m^2 (SD)	24.6 (2.7)	31.0 (8.4)	28.9 (5.2)

Note: For trial 2, patient demographic data are presented according to which device they were randomized to first.

Abbreviations: BMI, body mass index; N/A, not assessed; SD, standard deviation; AI, autoinjector; PFS, prefilled syringe.

Figure 1 Mean (± standard deviation) peginterferon alfa-2a concentration-time profile after single dose administered via the disposable autoinjector on linear (A) and log (B) scales.

Figure 2 Mean (± standard deviation) exposure from previous peginterferon alfa-2a healthy volunteer and patient studies.

Table 3 Single-dose pharmacokinetic parameters of peginterferon alfa-2a after administration via disposable autoinjector compared with historic studies

Parameter (units)	N	Mean ± SD	%CV	Historic studies
				Healthy volunteer studies*		Hepatitis C patient studies†
				Mean, range %	CV, range	Mean, range %	CV, range
Tmax (hours)	45	78.7 ± 43.7	55.5	78.0–102	28.0–48.0	57.0–105.0	35.0–70.2
Cmax (ng/mL)	45	16.1 ± 5.3	33.1	9.0–14.2	17.6–38.8	8.0–15.4	26.7–62.4
AUC0–168 h (ng · hour/mL)	45	1996 ± 613	30.7	950–1743	26.3–50.2	1009–1820	32.2–79.3
AUC0–last (ng · hour/mL)	45	2736 ± 1054	38.5
AUC0–∞ (ng · hour/mL)	43	3048 ± 1062	34.9
t1/2 (hours)	43	67.8 ± 36.3	53.5
Vz/F (L)	43	5.9 ± 2.9	49.5
Cl/F (mL/hour)	43	67.5 ± 27.1	40.1

* Notes: NP15537, NP15762, NP15989, NP15580, NP15538;

† NV15489, NV15495, NV15496, NV15497, NP17354, and NP17355.

Abbreviations: AUC, area under the concentration-time curve; C_max, observed maximum serum concentration; Cl/F, apparent total body clearance; T_max, time to C_max; t_½, terminal elimination half-life; V_z/F, apparent volume of distribution; %CV, percent coefficient of variation; AI, autoinjector; PFS, prefilled syringe.

Table 4 Summary of injection-method observational survey responses by study staff

n (%)	Injection 1		Injection 2		Injection 3
	AI n = 60	PFS n = 59	AI n = 58	PFS n = 59	AI n = 57	PFS n = 59
Patients exhibited nervousness prior to injection	11 (18)	14 (24)	0	3 (5)	1 (2)	2 (3)
Patients exhibited difficulty initiating injection	7 (12)	10 (17)	0	2 (3)	0	2 (3)
Patients appeared confident performing the injection	58 (97)	46 (78)	58 (100)	57 (97)	57 (100)	58 (98)
Patients successfully followed instructions	58 (97)	54 (92)	53 (91)	53 (90)	55 (96)	56 (95)
Patients experienced technical difficulties with device	7 (12)	2 (3)	5 (9)	1 (2)	3 (5)	3 (5)
Patients withdrew device before completion of injection	4 (7)	0	1 (2)	0	0	1 (2)
Patients exhibited pain/discomfort on injection	0	2 (3)	0	1 (2)	0	2 (3)
Patients appeared satisfied using device	60 (100)	51 (86)	58 (100)	55 (93)	57 (100)	56 (95)
Patients exhibited frustration with device	1 (2)	2 (3)	0	2 (3)	0	2 (3)

Notes: Results summarized for each injection (1, 2, or 3) by injection method used (disposable AI or PFS), regardless of timing (weeks 1–3 vs weeks 4–6).

Abbreviations: AI, autoinjector; PFS, prefilled syringe.

Table 5 Summary of patient subjective assessment of the injection method*

The patient	Injection 1		Injection 2		Injection 3
	AI n = 60	PFS n = 59	AI n = 59	PFS n = 59	AI n = 57	PFS n = 59
Was concerned about using the device preinjection	15 (25)	10 (17)	0	3 (5)	0	2 (3)
Was comfortable using the device	56 (93)	52 (88)	58 (100)	55 (93)	57 (100)	58 (98)
Found instructions easy to follow	60 (100)	59 (100)	58 (100)	59 (100)	57 (100)	59 (100)
Reported problems with the device	4 (7)	0	1 (2)	2 (3)	0	2 (3)
Reported problems performing injection	3 (5)	1 (2)	4 (7)	0	1 (2)	0
Reported pain or discomfort	2 (3)	8 (14)	0	3 (5)	0	4 (7)

* Note: Results summarized for each injection (1, 2, or 3) by injection method used (disposable AI or PFS), regardless of timing (weeks 1–3 vs weeks 4–6).

Abbreviations: AI, autoinjector; PFS, prefilled syringe.