A Fixed-Dose Combination Of Gemigliptin And Rosuvastatin Exhibits Similar Pharmacokinetics, Pharmacodynamics, And Safety Compared To That Of A Loose Combination In Healthy Subjects

Figures & data

Table 1 Demographic Characteristics Of The Subjects

	Sequence A (N = 20)	Sequence B (N = 20)	p-value
Age (years)	28.5 ± 5.3 (21–42)	28.1 ± 5.6 (21–44)	0.6640*
Height (cm)	176.4 ± 7.0 (165–186)	173.5 ± 5.3 (161–180)	0.1753*
Weight (kg)	72.3 ± 9.2 (56.2–87.2)	68.8 ± 7.3 (53.0–85.6)	0.1996**
BMI (kg/m^2)	23.2 ± 2.3 (18.5–26.9)	22.9 ± 2.1 (18.3–27.0)	0.6103**

Notes: Data are presented as arithmetic mean ± standard deviation. (min-max). Sequence A was first administered the loose combination of gemigliptin (50 mg) and rosuvastatin (20 mg), followed by the fixed-dose combination of gemigliptin/rosuvastatin 50/20 mg, and sequence B was administered in the reverse order. * P-value was obtained from Mann–Whitney U-test. ** P-value was obtained from two-sample t-test.

Table 2 Pharmacokinetic Parameters Of Rosuvastatin, Gemigliptin, And LC15-0636 After Administration Of Gemigliptin (50 mg) And Rosuvastatin (20 mg) As A Fixed-Dose Combination Or Loose Combination

Parameter	Rosuvastatin			Gemigliptin			LC15-0636
	FDC^a (N = 37)	LC^b (N = 37)	Geometric Mean Ratio* (90% CI)	FDC^a (N = 37)	LC^b (N = 37)	Geometric mean Ratio* (90% CI)	FDC^a (N = 37)	LC^b (N = 37)	Geometric Mean Ratio* (90% CI)
Tmax (h)	4.00 [1.50–8.00]	4.00 [0.50–6.02]	-	1.50 [0.50–5.02]	1.50 [0.50–5.00]	-	4.00 [1.00–5.02]	5.00 [1.00–6.00]	-
Cmax (μg/L)	27.85 ± 10.68	26.59 ± 12.20	1.0857 (0.9647–1.2218)	71.89 ± 22.59	66.29 ± 21.51	1.0791 (0.9869–1.1800)	10.70 ± 2.34	10.68 ± 2.45	1.0038 (0.9344–1.0785)
AUClast (h·μg/L)	285.78 ± 96.14	280.39 ± 94.42	1.0184 (0.9530–1.0882)	878.37 ± 217.67	842.40 ± 121.46	1.0233 (0.9605–1.0901)	278.03 ± 54.83	268.70 ± 36.83	1.0248 (0.9749–1.0773)
AUCinf (h·μg/L)	295.89 ± 94.87	291.40 ± 94.61	1.0184 (0.9596–1.0807)	968.83 ± 423.31	894.85 ± 132.09	1.0358 (0.9510–1.1281)	353.24 ± 183.33	324.19 ± 47.06	1.0335(0.9512–1.1230)
t1/2 (h)	11.33 ± 2.59	12.63 ± 4.12	-	18.92 ± 6.79	18.45 ± 1.73	-	28.69 ± 12.17	28.06 ± 4.88	-
CL/F (L/h)	75.89 ± 29.82	77.29 ± 29.09	-	56.51 ± 14.82	57.09 ± 8.63	-	-	-	-
Vd/F (L)	1207.95 ± 437.89	1422.75 ± 796.43	-	1473.26 ± 359.25	1510.09 ± 209.17	-	-	-	-
Metabolic ratio**	-	-	-	-	-	-	0.33 ± 0.06	0.32 ± 0.06	-

Notes: Data are presented as arithmetic mean ± standard deviation (SD) except for T_max, for which median [min–max] is presented. *Values expressed as geometric mean ratio (90% Confidence interval, CI) of FDC to loose combination. **Ratio of AUC_last for metabolite (LC15-0636) to parent drug (gemigliptin). Values are presented as mean ± SD. ^aFDC: fixed-dose combination of gemigliptin/rosuvastatin 50/20 mg. ^bLC: loose combination of gemigliptin 50 mg and rosuvastatin 20 mg.

Abbreviations: AUC_inf, area under the concentration–time curve from 0 to infinity; AUC_last, area under the concentration–time curve from 0 to the last measurable timepoint; CI, confidence interval; CL/F, apparent clearance; C_max, maximum concentration; GMR, geometric mean ratio of FDC to separate tablets; T_max, time to reach the C_max; t_1/2, terminal half-life; and V_d/F, apparent volume of distribution after oral dosing.

Figure 1 Mean plasma concentration-time profiles of (A) gemigliptin and LC15-0636 and (B) rosuvastatin after a single administration of a fixed-dose combination and loose combination of gemigliptin 50 mg and rosuvastatin 20 mg. Error bars represent standard deviations.

Table 3 Comparison Of Plasma DPP-4 Activity Inhibition From Baseline After Administration Of Gemigliptin (50 mg) And Rosuvastatin (20 mg) As A Fixed-Dose Combination Or Loose Combination

Parameter	DPP-4 Activity Inhibition (%)
	Fixed-Dose Combination	Loose Combination	Geometric Mean Ratio*
	(N = 37)	(N = 37)	(90% CI)
AUEClast (%·h)	4838.76 ± 442.36	4826.99 ± 511.14	1.0041 (0.9797–1.0291)
Imax (%)	93.35 ± 2.58	92.65 ± 3.78	1.0082 (0.9956–1.0210)

Note: *Values expressed as geometric mean ratio (90% CI) of fixed-dose combination to loose combination. Data are presented as arithmetic mean ± standard deviation.

Abbreviations: AUEC_last, area under the inhibition of DPP activity–time curve from 0 to the last measurable timepoint; CI, confidence interval; I_max, maximum inhibition of DPP-4 activity.

Figure 2 Mean plasma DPP-4 activity inhibition from baseline–time profiles after administration of a fixed-dose combination and loose combination of gemigliptin and rosuvastatin. Error bars represent standard deviations.