Investigation of the impact of urine handling procedures on interpretation of urinalysis findings and product safety in subjects treated with ezogabine

Figures & data

Figure 1 Design of study RTG114137.

Abbreviation: PK, pharmacokinetics.

Table 1 Incidence of urinalysis abnormalities in Study 303

	Urine samples (n = 35)
	Baseline	Stored laboratory
		A	B
Not clear, n (%)	10 (29)	35 (100)	16 (46)
Discolored, n (%)	12 (34)	10 (29)	1 (3)
Protein positive, n (%)	2 (6)	9 (26)	2 (6)

Table 2 Baseline demographic characteristics for Study RTG114137

Safety and pharmacodynamic population	Total (n = 33)
Mean age, years	47.4
Gender, n (%)
Female	8 (24)
Race, n (%)
White/European heritage	18 (55)
Black/African heritage	11 (33)
Mean body mass index (kg/m^2)	26.9

Table 3 Incidence of urinalysis abnormalities in Study RTG114137

	Subjects (%)
	Fresh	Stabilizer 1		Stabilizer 2
		24 hours	72 hours	24 hours	72 hours
Protein in urine
Non-restricted fluid days
Day 11 (ezogabine 600 mg)	0	3	3	3	3
Day 18 (ezogabine 750 mg)	0	0	3	3	3
Day 25 (ezogabine 900 mg)	4	4	4	8	4
Restricted fluid day
Day 13 (ezogabine 600 mg)	7	32	32	90	55
Crystals in urine
Non-restricted fluid days
Day 11 (ezogabine 600 mg)	0	3	0	3	3
Day 18 (ezogabine 750 mg)	3	0	0	0	0
Day 25 (ezogabine 900 mg)	4	0	4	0	4
Restricted fluid day
Day 13 (ezogabine 600 mg)	13	23	39	0	3
Urine color change
Non-restricted fluid days
Day 11 (ezogabine 600 mg)	–	13	31	31	22
Day 18 (ezogabine 750 mg)	–	23	73	17	10
Day 25 (ezogabine 900 mg)	–	20	56	0	16
Restricted fluid day
Day 13 (ezogabine 600 mg)	–	0	7	29	65

Figure 2 Effect of fluid restriction on the density of urine from healthy volunteers receiving ezogabine in Study RTG114137.

Abbreviation: SD, standard deviation.

Table 4 Adverse events occurring in ≥2 subjects by ezogabine dose for Study RTG114137

Preferred term	Ezogabine daily dose
	n (%)
	300 mg n = 33	450 mg n = 32	600 mg n = 32	750 mg n = 31	900 mg n = 19	Total n = 33
Subject with any drug-related adverse event	12 (36)	14 (44)	24 (75)	18 (58)	12 (63)	31 (94)
Dizziness	2 (6)	2 (6)	7 (22)	7 (23)	1 (5)	14 (42)
Euphoric mood	6 (18)	3 (9)	4 (13)	1 (3)	2 (11)	14 (42)
Somnolence	3 (9)	5 (16)	1 (3)	3 (10)	1 (5)	12 (36)
Headache	1 (3)	0	4 (13)	7 (23)	2 (11)	11 (33)
Memory impairment	0	1 (3)	5 (16)	3 (10)	0	9 (27)
Oral paresthesia	0	1 (3)	2 (6)	5 (16)	0	8 (24)
Confusional state	0	0	2 (6)	3 (10)	3 (16)	7 (21)
Dysarthria	2 (6)	0	1 (3)	4 (13)	0	7 (21)
Chromaturia	0	0	2 (6)	3 (10)	1 (5)	6 (18)
Disturbance in attention	1 (3)	0	2 (6)	3 (10)	0	6 (18)
Dry mouth	0	0	2 (6)	1 (3)	2 (11)	5 (15)
Heterophoria	0	0	2 (6)	1 (3)	2 (11)	5 (15)
Constipation	1 (3)	2 (6)	0	1 (3)	0	4 (12)
Abnormal coordination	0	0	2 (6)	2 (6)	0	4 (12)
Nausea	0	0	3 (9)	2 (6)	0	4 (12)
Paresthesia	0	0	1 (3)	3 (10)	0	4 (12)
Abdominal pain	0	1 (3)	0	2 (6)	0	3 (9)
Fatigue	0	0	1 (3)	2 (6)	0	3 (9)
Blurred vision	0	0	2 (6)	1 (3)	1 (5)	3 (9)
Affect lability	0	2 (6)	0	0	0	2 (6)
Arthralgia	0	0	1 (3)	2 (6)	0	2 (6)
Ataxia	0	0	0	2 (6)	0	2 (6)
Decreased appetite	0	0	0	2 (6)	0	2 (6)
Pollakiuria	2 (6)	0	0	0	0	2 (6)