Telbivudine vs tenofovir in hepatitis B e antigen-negative chronic hepatitis B patients: OPTIMA roadmap study

Table 1 Demographic and baseline characteristics, randomised population

Patients characteristics	Telbivudine (n = 121)	Tenofovir (n = 120)
Age, mean (SD), yr	42.1 (11.5)	43.3 (12.6)
Median (min-max)	42.0 (19-70)	44.0 (18-73)
Male gender, n (%)	86 (71.1)	82 (68.3)
Race, Caucasian, n (%)	117 (96.7)	118 (98.3)
Body mass index, mean (SD), kg/m2	25.8 (4.1)	25.7 (4.0)
Median (min-max)	25.6 (16.5-40.4)	25.2 (18.4-39.8)
Genotype, n (%)
A	6 (5.0)	2 (1.7)
B	1 (0.8)	0 (0.0)
C	0 (0.0)	1 (0.8)
D	104 (86.0)	110 (91.7)
G	1 (0.8)	0 (0.0)
Other	1 (0.8)	0 (0.0)
Unknown	8 (6.6)	7 (5.8)
HBV DNA, mean (SD), log10 copies/mL	6.2 (1.5)	6.0 (1.4)
Median (min-max)	6.1 (3.2-9.5)	5.9 (2.5-9.9)
< 7 log10, n (%)	85 (70.2)	86 (71.7)
≥ 7 log10, n (%)	36 (29.8)	34 (28.3)
Serum alanine aminotransferase, mean (SD), IU/L	79.8 (84.1)	78.2 (86.1)
Median (min-max)	53.0 (13-494)	49.0 (5-568)
Serum aspartate aminotransferase, mean (SD), IU/L	54.0 (52.8)	52.5 (47.1)
Median (min-max)	35.0 (13-347)	35.0 (13-322)
Creatine phosphokinase, mean (SD), IU/L	118.6 (64.4)	160.1 (299.3)
Median (min-max)	104.0 (35-430)	111.0 (36-2976)
eGFR1, mean (SD), (mL/min per 1.73 m2)	97.4 (17.9)	95.8 (16.4)
Median (min-max)	96.6 (60.9-147.1)	94.2 (60.5-138.4)

¹eGFR: Estimated glomerular filtration rate (modification of diet in renal disease formula). HBV: Hepatitis B virus; SD: Standard deviation.

Table 2 Virologic response, roadmap intent-to-treat population

Parameters	Telbivudine (n = 113)	Tenofovir (n = 117)	Difference between arms and 95%CI
Patients achieving HBV DNA < 300 copies/mL (51 IU/mL) at week 52, n (%)
± 7 d protocol-prespecified visit window	104 (91.9)	111 (95.0)	-3.1% (-9.4%, 3.1%)1
Treating missing as failure	103 (91.0)	111 (95.0)	-4.0% (-10.5%, 2.5%)1
28 d imputation	105 (92.7)	111 (95.0)	-2.3% (-8.3%, 3.8%)1
Last observation carried forward	108 (95.4)	116 (99.2)	-3.8% (-7.9%, 0.4%)1
Change from baseline in HBV DNA levels (log10 copies/mL) by visit, mean (SD)			P-value
Week 24	-4.001 (1.256)	-4.122 (1.165)	P < 0.00012
Week 52	-4.356 (1.473)	-4.305 (1.343)	P < 0.00012
Week 104	-4.281 (1.753)	-4.349 (1.382)	P < 0.00012

¹Percentages and 95%CIs were calculated using Mantel-Haenszel weighted estimates stratified by baseline HBV DNA and alanine aminotransferase levels;

²P-values were calculated using paired t-test comparing post-baseline timepoints to baseline timepoints. CI: Confidence interval; HBV: Hepatitis B virus; SD: Standard deviation.

Table 3 Summary of safety results, safety population n (%)

Safety parameters	Telbivudine			Tenofovir
	Monotherapy (n = 98)	Intensification with tenofovir (n = 22)	Overall (n = 120)	Monotherapy (n = 109)	Intensification with telbivudine (n = 11)	Overall (n = 120)
Any AE	69 (70.4)	17 (77.3)	86 (71.7)	75 (68.8)	8 (72.7)	83 (69.2)
AE related to drug	36 (36.7)	11 (50.0)	47 (39.2)	21 (19.3)	6 (54.5)	27 (22.5)
AE leading to drug discontinuation	2 (2.0)	0 (0.0)	2 (1.7)	5 (4.6)	0 (0.0)	5 (4.2)
Any SAE	6 (6.1)	5 (22.7)	11 (9.2)	11 (10.1)	2 (18.2)	13 (10.8)
SAE related to drug	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	1 (9.1)	1 (0.8)
Death	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
AEs related to drug occurring in ≥ 2% of patients in any treatment arm
Blood CPK increased	23 (23.5)	8 (36.4)	31 (25.8)	13 (11.9)	3 (27.3)	16 (13.3)
Nausea	6 (6.1)	2 (9.1)	8 (6.7)	0 (0.0)	2 (18.2)	2 (1.7)
Myalgia	7 (7.1)	1 (4.5)	8 (6.7)	0 (0.0)	0 (0.0)	0 (0.0)
Alanine aminotransferase increased	2 (2.0)	0 (0.0)	2 (1.7)	3 (2.8)	1 (9.1)	4 (3.3)
Proteinuria	2 (2.0)	0 (0.0)	2 (1.7)	4 (3.7)	0 (0.0)	4 (3.3)
Aspartate aminotransferase increased	3 (3.1)	0 (0.0)	3 (2.5)	2 (1.8)	0 (0.0)	2 (1.7)
Any AE of special interest	35 (35.7)	11 (50.0)	46 (38.3)	23 (21.1)	4 (36.4)	27 (22.5)
AEs of special interest occurring in ≥ 2% of patients in any treatment arm
Blood CPK increased	24 (24.5)	10 (45.5)	34 (28.3)	17 (15.6)	3 (27.3)	20 (16.7)
Myalgia	10 (10.2)	2 (9.1)	12 (10.0)	2 (1.8)	1 (9.1)	3 (2.5)
Alanine aminotransferase increased	5 (5.1)	0 (0.0)	5 (4.2)	5 (4.6)	1 (9.1)	6 (5.0)
Proteinuria	3 (3.1)	0 (0.0)	3 (2.5)	4 (3.7)	0 (0.0)	4 (3.3)
Any patient with muscle event	12 (12.2)	2 (9.1)	14 (11.7)	2 (1.8)	1 (9.1)	3 (2.5)
Experiencing new-onset Grade 3/4 abnormal CPK within the study	4 (4.1)	1 (4.5)	5 (4.2)	0 (0.0)	0 (0.0)	0 (0.0)
Experiencing new-onset Grade 1/2 abnormal CPK within the study	6 (6.1)	1 (4.5)	7 (5.8)	1 (0.9)	1 (9.1)	2 (1.7)
Any patient with new-onset Grade 3/4 CPK episode within the study	17 (17.3)	2 (9.1)	19 (15.8)	3 (2.8)	2 (18.2)	5 (4.2)
Episode not resolved	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

AE: Adverse event; CPK: Creatine phosphokinase; SAE: Serious adverse event.