Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium) and VIMOVO^® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium) in healthy volunteers

Figures & data

Table 1 Summary of pharmacokinetic results for naproxen and esomeprazole

Variable (unit)	HCP1004 (N=66)		VIMOVO^® (N=66)
	Mean ± SD	CV (%)	Mean ± SD	CV (%)
Naproxen
Cmax (µg/mL)	61.67±15.16	24.59	61.85±14.54	23.51
AUC0−t (h·µg/mL)	1,206.52±166.46	13.80	1,211.44±170.01	14.03
AUCinf (h·µg/mL)	1,369.64±234.25	17.10	1,364.26±229.51	16.82
Tmax*	5.00 (3.00–24.03)		5.00 (3.00–24.02)
t1/2	22.74±4.08		22.17±3.49
Esomeprazole
Cmax (ng/mL)	658.21±510.91	77.62	595.09±364.23	61.21
AUC0−t (h·ng/mL)	1,109.11±1,111.59	100.22	1,015.12±52.98	93.88
AUCinf (h·ng/mL)	1,129.59±1,131.10	100.13	1,034.80±970.05	93.74
Tmax*	0.50 (0.33–2.00)		0.43 (0.17–1.00)
t1/2	1.20±0.41		1.20±0.43

Notes: All values are presented as the arithmetic mean ± standard deviation.

* Median (minimum – maximum).

Abbreviations: N, number of subjects; SD, standard deviation; CV, coefficient of variation; C_max, maximum plasma concentration; AUC_0−t, area under the concentration–time curve from time 0 to the last measurable time point; T_max, time to reach the maximum plasma concentration; t_1/2, apparent elimination half-life.

Figure 1 Mean plasma concentration–time profiles of naproxen and esomeprazole.

Notes: (A) Mean plasma concentration–time profiles of naproxen after a single dose of HCP1004 or VIMOVO^®, and (B) mean plasma concentration–time profiles of esomeprazole after a single dose of HCP1004 or VIMOVO^®.
Abbreviations: N, number of subjects; hr, hours.

Figure 2 Individual changes in pharmacokinetic parameters.

Notes: (A) C_max of naproxen; (B) AUC_0−t of naproxen; (C) C_max of esomeprazole; and (D) AUC_0−t of esomeprazole.
Abbreviations: C_max, maximum plasma concentration; AUC_0−t, area under the concentration–time curve from time 0 to the last measurable time point.

Table 2 Pharmacokinetic comparison of naproxen and esomeprazole by treatment

Parameter	Geometric mean		Point estimate (T/R ratio)	90% confidence interval
	HCP1004 (N=66)	VIMOVO^® (N=66)
Naproxen
Cmax (µg/mL)	59.57	59.97	0.99	0.94–1.06
AUC0−t (h·µg/mL)	1,194.91	1,199.54	1.00	0.98–1.01
Esomeprazole
Cmax (ng/mL)	463.19	470.03	0.99	0.82–1.18
AUC0−t (h·ng/mL)	711.63	685.63	1.04	0.91–1.18

Abbreviations: N, number of subjects; T, test drug HCP1004; R, reference drug VIMOVO^®; C_max, maximum plasma concentration; AUC_0−t, area under the concentration–time curve from time 0 to the last measurable time point.

Table 3 Incidence of AEs after a single dose of HCP1004 or VIMOVO^®

System organ class/preferred term	Number of AEs
	VIMOVO^® (N= 66)		HCP1004 (N= 67)		% of subjects
Causal relationship	Related	Not related	Related	Not related
Number of subjects with AEs	2	2	4	4	17.9
Gastrointestinal disorders	1		3		4.5
Diarrhea	1		1		3.0
Dyspepsia			2		1.5
General disorder and administration site conditions			1	1	3.0
Catheter site pain				1	1.5
Feeling hot			1		1.5
Nervous system disorders	1	1	1		4.5
Headache	1	1	1		4.5
Respiratory, thoracic, and mediastinal disorders		2		3	6.0
Tonsillar hypertrophy				1	1.5
Dysphonia				1	1.5
Oropharyngeal pain				1	1.5
Epistaxis		1			1.5
Rhinorrhea		1			1.5
Skin and subcutaneous tissue disorders				1	1.5
Hyperhidrosis				1	1.5

Abbreviations: AEs, adverse events; N, number of subjects.

Table S1 Comparison of AEs by treatment group

	Treatment			P-value
	VIMOVO^® (N=66)	HCP1004 (N=67)	Total (N=67)
Number of subjects with at least one AE	4	8	12	0.365**
(%)	6.1	11.9	17.9
Number of AEs	5	10	15	0.302*
Number of subjects with at least one drug-related AE	2	4	6	0.688**
(%)	3.0	6.0	9.0
Number of drug-related AEs	2	5	7	0.453**

Notes:

* Chi-squared test;

** Fisher’s exact test.

Abbreviations: AEs, adverse events; N, number of subjects.