Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel-group, single-dose, Phase I study

Figures & data

Figure 1. Subject disposition.

Table 1. Baseline subject demographics (safety analysis set).

	CT-P13 (n = 71)	EU-RMP (n = 71)	US-RMP (n = 71)
Age (years)
Median (range)	41.0 (22–55)	45.0 (24–55)	41.0 (18–55)
Sex (n, %)
Male	61 (85.9)	61 (85.9)	61 (85.9)
Female	10 (14.1)	10 (14.1)	10 (14.1)
Race (n, %)
Caucasian	71 (100)	69 (97.2)	70 (98.6)
Other	0	2 (2.8)	1 (1.4)
Height (cm)
Median (range)	180.0 (158–193)	177.0 (159–200)	178.0 (154–196)
Weight (kg)
Median (range)	81.4 (60.4–99.2)	77.0 (55.6–99.3)	78.1 (55.4–99.9)
BMI (kg/m^2)
Median (range)	25.0 (18.8–29.7)	25.3 (18.6–29.6)	24.5 (18.8–29.7)

EU-RMP: Europe-approved reference medicinal product; US-RMP: US-licensed reference medicinal product.

Figure 2. Mean ± standard deviation serum concentrations of three formulations of infliximab over time.

Table 2. Primary pharmacokinetic end points between three formulations of infliximab: CT-P13, EU-RMP and US-RMP.

Test (T)	Reference (R)	Parameter	Geometric mean		GMR% (T/R)	90% CI
			T	R
		Cmax (µg/ml)	132.29	125.95	105.03	100.64–109.62
CT-P13 (n = 70)	EU-RMP (n = 71)	AUClast (h*µg/ml)	32526.76	31949.76	101.81	96.36–107.56
		AUCinf (h*µg/ml)	34313.46	34053.52	100.76	94.37–107.59
		Cmax (µg/ml)	132.29	124.43	106.32	101.86–110.99
CT-P13 (n = 70)	US-RMP (n = 70)	AUClast (h*µg/ml)	32526.76	33041.50	98.44	93.16–104.03
		AUCinf (h*µg/ml)	34313.46	35564.16	96.48	90.36–103.02
		Cmax (µg/ml)	125.95	124.43	101.23	96.99–105.65
EU-RMP (n = 71)	US-RMP (n = 70)	AUClast (h*µg/ml)	31949.76	33041.50	96.70	91.52–102.16
		AUCinf (h*µg/ml)	34053.52	35564.16	95.75	89.72–102.19

AUC_inf: Area under the concentration–time curve from time zero to infinity; AUC_last: Area under the concentration–time curve from time zero to last quantifiable concentration; C_max: Maximum serum concentration; EU-RMP: Europe-approved reference medicinal product; GMR: Geometric mean ratio; US-RMP: US-licensed reference medicinal product.

Table 3. Mean (± standard deviation) values for the secondary pharmacokinetic end points (pharmacokinetic analysis set).

	CT-P13 (n = 70)	EU-RMP (n = 71)	US-RMP (n = 70)
Vz (ml)	5441.34 (1656.29)	5584.02 (1579.16)	5670.80 (1361.15)
t1/2 (day)	13.42 (5.27)	13.82 (5.28)	14.70 (4.68)
CL (ml/h)	12.71 (3.51)	12.53 (3.25)	11.72 (2.72)
MRT (h)	334.79 (72.89)	344.18 (65.18)	354.99 (57.42)

CL: Total body clearance; EU-RMP: Europe-approved reference medicinal product; MRT: Mean residence time; t_1/2: Terminal half-life; US-RMP: US-licensed reference medicinal product; V_z: Volume of distribution during the terminal phase.

Table 4. Treatment-related TEAEs. Data are shown for TEAEs that occurred in ≥3% of subjects in any treatment group (safety analysis set).

	CT-P13 (n = 71)	EU-RMP (n = 71)	US-RMP (n = 71)
Nasopharyngitis	11 (15.5)	11 (15.5)	16 (22.5)
Rhinitis	5 (7.0)	1 (1.4)	4 (5.6)
Fatigue	4 (5.6)	1 (1.4)	2 (2.8)
Flatulence	4 (5.6)	0	0
Headache	3 (4.2)	3 (4.2)	6 (8.5)
Abdominal pain	3 (4.2)	0	1 (1.4)
Oropharyngeal pain	1 (1.4)	1 (1.4)	3 (4.2)
Oral herpes simplex	0	0	3 (4.2)

EU-RMP: Europe-approved reference medicinal product; TEAEs: Treatment-emergent adverse events; US-RMP: US-licensed reference medicinal product.