Effect of Efavirenz on the Pharmacokinetics of SHR6390 in Healthy Volunteers

Figures & data

Figure 1 Study flow chart.

Table 1 Plasma Pharmacokinetic Parameters of SHR6390 Following Monoadministration and Coadministration with Efavirenz

Pharmacokinetic parameters (Unit)	Mean±SD (CV %)
	SHR6390 (N=20)	SHR6390 with efavirenz (N=17)^b
Cmax(ng/mL)	62.7±16.2 (25.9%)	35.3±9.8 (27.8%)
AUC0–t (h*ng/mL)	1970±436 (22.1%)	688±204 (29.6%)
AUC0–∞ (h*ng/mL)	2140±495 (23.2%)	719±215 (29.9%)
Tmax (h)^a	5.0 (2.0, 6.0)	4.0 (1.0, 8.0)
t1/2 (h)	43.7±5.66	29.3±4.33
CL/F (L/h)	74.4±20.3	234±97.8
Vd (L)	4610±970	9600±3250

Notes: SD standard deviation, CV% percent coefficient of variation of mean, N number of subjects with available data in pharmacokinetic analysis, AUC_0–∞ area under the plasma concentration-time curve from time zero to infinity, AUC_0–t area under the plasma concentration-time curve from the time zero to the last measurable plasma concentration, C_max maximum observed plasma concentration, T_max time to maximum plasma concentration, t_1/2 half-life. ^aPresented as median (minimum-maximum). ^bThree subjects dropped out before the administration of SHR6390 with efavirenz.

Table 2 Treatment Ratio Geometric Mean Ratios (GMR, SHR6390+efavirenz versus SHR6390 Alone) with 90% Confidence Interval for SHR6390

PK parameters	Geometric mean^a
	SHR6390 with efavirenz (N=17)	SHR6390 (N=20)	Ratio	90% CI
Cmax(ng/mL)	34.026	60.567	0.562	0.482, 0.654
AUC0–t (h*ng/mL)	652.682	1917.808	0.340	0.289, 0.400
AUC0–∞ (h*ng/mL)	681.868	2079.714	0.328	0.278, 0.386

Notes: AUC_0–∞ area under the plasma concentration-time curve from time zero to infinity, AUC_0–t area under the plasma concentration-time curve from time zero to the last time point with a measurable concentration, CI confidence interval, C_max maximum observed plasma concentration. ^aLeast squares method.

Figure 2 The linear and semilogarithmic scales of mean plasma concentration-time curves after subjects received a single dose (150 mg) of SHR6390 orally and together with 600 mg efavirenz.

SHR6390.

SHR6390 with efavirenz.

Table 3 Summary of Adverse Events After the Study Drug Administration

Treatment Adverse event	SHR6390 (N=20)	Efavirenz (N=20)	SHR6390 + efavirenz (N=17)	Total (N=20)
Dizziness	0 (0)	14 (14)	0 (0)	14 (14)
Hypoesthesia^a	0 (0)	1 (1)	0 (0)	1 (1)
Headache	0 (0)	1 (1)	0 (0)	1 (1)
White blood cell count decrease	1 (1)	0 (0)	3 (3)	4 (4)
Neutrophil count decrease	1 (1)	0 (0)	1 (1)	2 (2)
Blood pressure increase^a	1 (1)	1 (1)	0 (0)	1 (2)
Alanine aminotransferase increase	0 (0)	1 (1)	0 (0)	1 (1)
Aspartate aminotransferase increase	0 (0)	0 (0)	1 (1)	1 (1)
QRS interval prolong^a	0 (0)	1 (1)	0 (0)	1 (1)
Heart rate increase^a	1 (1)	0 (0)	0 (0)	1 (1)
Blood non-binding bilirubin increase	1 (1)	0 (0)	0 (0)	1 (1)
Oral ulcer^a	1 (1)	4 (4)	1 (1)	4 (6)
Nausea	0 (0)	3 (3)	0 (0)	3 (3)
Constipation^a	0 (0)	1 (1)	0 (0)	1 (1)
Non-infectious gingivitis^a	0 (0)	1 (1)	0 (0)	1 (1)
Abnormal dreaming	0 (0)	4 (5)	0 (0)	4 (5)
Insomnia	0 (0)	1 (1)	0 (0)	1 (1)
Upper respiratory tract infection^a	0 (0)	2 (2)	1 (1)	3 (3)
Conjunctivitis^a	0 (0)	1 (1)	0 (0)	1 (1)
Allergic dermatitis	0 (0)	2 (2)	0 (0)	2 (2)
Rash	0 (0)	1 (1)	0 (0)	1 (1)
Acne^a	0 (0)	1 (1)	0 (0)	1 (1)
Anemia^a	0 (0)	0 (0)	2 (2)	2 (2)
Anorexia	0 (0)	1 (1)	0 (0)	1 (1)
Cough^a	0 (0)	0 (0)	2 (2)	1 (1)
Ventricular extrasystole	1 (1)	0 (0)	0 (0)	1 (1)
Total	4 (7)	16 (42)	7 (10)	19 (59)

Notes: Data are presented as the number of subjects (number of events). ^aConsidered as “not related” to the study drugs.

Data Sharing Statement

The data that support the findings of this study are not available due to confidentiality.