Phase I, Single-Dose Study to Assess the Pharmacokinetics and Safety of Suramin in Healthy Chinese Volunteers

Figures & data

Figure 1 Study design. Placebo-treated subjects were followed for at least 28 days until unblinding permits in each dose group. PK sampling time was up to 140 days for suramin treatment cohorts to better characterize the terminal phase, given the long elimination half-life based on emerging data.

Table 1 Baseline Characteristics of the Randomized Study Population (n = 36)

Characteristic	Placebo n = 6	Suramin			Total n = 36
		10 mg/kg (n = 10)	15 mg/kg (n = 10)	20 mg/kg (n = 10)
Age, mean (SD), y	24.8 (2.9)	25.4 (2.7)	28.2 (4.6)	26.1 (4.1)	26.2 (3.9)
Height, mean (SD), m	1.65 (1.1)	1.64 (7.4)	1.64 (7.7)	1.65 (6.6)	1.64 (7.3)
Weight, mean (SD), kg	61.4 (8.5)	59.2 (6.6)	58.3 (8.7)	60.5 (7.8)	60.3 (7.3)
BMI, mean (SD), kg/m^2	22.4 (2.2)	22.0 (1.7)	21.6 (1.9)	22.2 (2.5)	22.1 (2.0)
Sex, No. (%)
Male	4 (66.7)	8 (80.0%)	6 (60.0%)	7 (70.0%)	25 (69.4%)
Female	2 (33.3)	2 (20%)	4 (40.0%)	3 (30.0%)	11 (30.6%)
Race, No. (%)
Asian	6 (100%)	10 (100%)	10 (100%)	10 (100%)	36 (100%)
Nation, No. (%)
Han	6 (100%)	10 (100%)	8 (80%)	8 (80%)	32 (88.9%)

Abbreviations: BMI, body mass index; SD, standard deviation.

Table 2 Pharmacokinetic Parameters of Suramin After Single-Dose Administration of Injected Suramin Sodium in Healthy Subjects

Parameters	Geometric Mean (Geometric CV%)			Slop β (95% CI)
	10 mg/kg n = 9	15 mg/kgn = 9	20 mg/kg n = 8
Cmax, μg/mL^a**	160 (9.6)	253 (10.9)	328 (6.5)	1.040 (0.908–1.171)
AUC0-140d, h·mg/mL^a**	13.4 (20.4)	23.8 (19.8)	33.7 (9.2)	1.334 (1.092–1.575)
AUC0-∞, h·mg/mL^a**	15.6 (28.9)	26.4 (19.9)	38.2 (14.6)	1.288 (1.004–1.573)
Tmax, hour^b	0.59 (0.50–0.59)	0.54 (0.49–1.0)	0.58 (0.50–0.58)
t1/2, hour	1050 (33.9)	1109 (22.9)	1174 (46.3)
CL, mL/hour	37.3 (26.5)	33.4 (26.2)	31.9 (11.4)
V, L	56.5 (23.3)	53.4 (36.7)	54.0 (42.6)
Urinary recovery in 7days (% of dose)	3.95 (1.57)	3.75 (0.83)	3.81 (0.73)

Notes: ^aPharmacokinetic parameters were logarithmically transformed prior to analysis of variance (ANOVA). ^bData was shown as median (min, max). **P<0.001: The difference of the PK parameters among different dose groups is considered to be statistically significant.

Abbreviations: AUC_0-∞, area under the plasma concentration–time curve from time 0 to infinity; AUC_0-140d, area under the plasma concentration–time curve from time 0 to 140 days; CL, apparent clearance; C_max, maximum observed concentration; T_max, time to C_max; t_1/2, terminal elimination phase half-life; V, apparent volume of distribution.

Figure 2 Mean concentration–time curve with standard deviation for suramin in healthy human subjects after a single dose.

Figure 3 Dose linearity plots of C_max and AUC parameters in a single ascending-dose study.

Table 3 Summary of Adverse Events

Adverse Event	Placebo n = 6	Suramin			Total (n = 36)
		Cohort 1	Cohort 2	Cohort 3
		10 mg/kg n = 10	15 mg/kg n = 10	20 mg/kg n = 10
Summary of AEs
Any AE, n (%)	5 (83.3%)	10 (100%)	10 (100%)	10 (100%)	35 (97.2%)
Moderate or severe AE, n (%)	0	0	2 (10%)	3 (30%)	5 (13.9%)
Severe AE, n (%)	0	0	0	0	0
SAE, n (%)	0	0	0 (10%)	1 (10%)	1 (2.7%)
Discontinuing or withdrawing due to an AE, n (%)	0	0	1 (10%)	0	1 (2.7%)
Treatment-related AE, n (%)	4 (66.7%)	5 (50%)	9 (90%)	7 (70%)	25 (69.4%)
Body as a whole
Infusion reaction	0	0	0	1
Infectious and infective disease
Conjunctivitis	0	0	0	1
Pharyngitis	0	0	1	0
Upper respiratory tract infection	1	3	1	5
Gastrointestinal disorders
Diarrhea	0	1	0	1
Nausea	0	0	1	0
Oral ulcer	0	0	1	0
Hemorrhoidal bleeding	1	0	0	0
Nervous system disorders
Abnormal sensation	0	0	0	1
Headache	1	0	1	0
Cardiovascular disorders
Sinus tachycardia	0	0	1	1
Sinus bradycardia	2	2	1	3
Supraventricular extrasystole	0	0	0	1
Ventricular extrasystole	1	0	0	0
Skin and subcutaneous tissue disorders
Rash	0	0	1	1
Pimple	0	0	1	0
Acne-like dermatitis	0	0	1	0
Pruritus	0	0	1	0
Vascular and lymphatic diseases
Low blood pressure	0	1	1	0
Hot flush	0	0	1	0
Pregnancy, puerperium and perinatal conditions
Pregnancy	0	0	1	0
Laboratory values
Elevated blood uric acid	0	1	0	0
Elevated serum alanine aminotransferase	1	2	2	0
Elevated serum aspartate aminotransferase	1	1	1	0
Elevated serum bilirubin	1	0	1	0
Elevated serum creatinine	0	0	0	2
Elevated serum total bile acid	1	0	1	1
Elevated serum triglyceride	0	2	4	2
Decreased fibrinogen	0	0	2	2
Decreased platelet	0	1	0	0
Decreased potassium	0	0	1	0
Neutropenia	0	1	2	1
Urinary protein positive	0	2	5	6
Urine erythrocyte positive	1	0	2	1
Urine white blood cell positive	0	2	5	6

Abbreviation: AE, adverse event.