Trial Outcomes & Findings for An Electrophysiological Study Of E2014 In Healthy Adult Male Japanese And Caucasian Subjects (NCT NCT00280384)

Results Overview

The pharmacodynamic effect of botulinum toxin type B (E2014) was evaluated based on the inhibition of EDB M-wave amplitude induced by stimulation of the deep peroneal nerve in the left ankles of the study participants. EDB M-wave amplitudes (mV) were measured at screening (baseline), and Day 1, Day 2, Day 4, Day 6, Day 8, Day 10, Day 14, Week 4, and Week 12. Rates of EDB M-wave amplitude reduction from baseline were then calculated at each time point. The maximum rates of EDB M-wave amplitude reduction from baseline were presented as a percentage.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

Baseline and Up to Week 12

Results posted on

2013-04-25

Participant Flow

Of the 94 participants screened (60 Japanese, 34 Caucasian), 57 (29 Japanese and 28 Caucasian) participants were admitted to the hospital. 9 (5 Japanese and 4 Caucasian) participants did not receive the study drug. 48 participants received the study drug (24 Japanese and 24 Caucasian) and were considered the treated population.

Participant milestones

Participant milestones
Measure	E2014 (Botulinum Toxin Type B) Placebo- Japanese A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 20 U - Japanese A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 100 U - Japanese A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 500 U - Japanese A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) Placebo - Caucasian A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 20 U - Caucasian A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 100 U - Caucasian A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 500 U - Caucasian A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.
Overall Study STARTED	6	6	6	6	6	6	6	6
Overall Study COMPLETED	6	6	6	6	6	6	6	6
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Electrophysiological Study Of E2014 In Healthy Adult Male Japanese And Caucasian Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	E2014 (Botulinum Toxin Type B) Placebo- Japanese n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 20 U - Japanese n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 100 U - Japanese n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 500 U - Japanese n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) Placebo - Caucasian n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 20 U - Caucasian n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 100 U - Caucasian n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 500 U - Caucasian n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	Total n=48 Participants Total of all reporting groups
Age Continuous	22.7 years STANDARD_DEVIATION 2.9 • n=5 Participants	28.0 years STANDARD_DEVIATION 5.4 • n=7 Participants	23.3 years STANDARD_DEVIATION 2.9 • n=5 Participants	22.2 years STANDARD_DEVIATION 2.6 • n=4 Participants	33.7 years STANDARD_DEVIATION 2.7 • n=21 Participants	34.5 years STANDARD_DEVIATION 3.7 • n=8 Participants	32.7 years STANDARD_DEVIATION 2.9 • n=8 Participants	29.3 years STANDARD_DEVIATION 2.6 • n=24 Participants	28.3 years STANDARD_DEVIATION 5.7 • n=42 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	6 Participants n=8 Participants	6 Participants n=8 Participants	6 Participants n=24 Participants	48 Participants n=42 Participants

PRIMARY outcome

Timeframe: Baseline and Up to Week 12

The pharmacodynamic effect of botulinum toxin type B (E2014) was evaluated based on the inhibition of EDB M-wave amplitude induced by stimulation of the deep peroneal nerve in the left ankles of the study participants. EDB M-wave amplitudes (mV) were measured at screening (baseline), and Day 1, Day 2, Day 4, Day 6, Day 8, Day 10, Day 14, Week 4, and Week 12. Rates of EDB M-wave amplitude reduction from baseline were then calculated at each time point. The maximum rates of EDB M-wave amplitude reduction from baseline were presented as a percentage.

Outcome measures

Outcome measures
Measure	E2014 (Botulinum Toxin Type B) Placebo- Japanese n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 20 U - Japanese n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 100 U - Japanese n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 500 U - Japanese n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) Placebo - Caucasian n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 20 U - Caucasian n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 100 U - Caucasian n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 500 U - Caucasian n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.
Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline	9.02 Percentage of Reduction Standard Deviation 13.51	48.53 Percentage of Reduction Standard Deviation 16.98	70.95 Percentage of Reduction Standard Deviation 6.12	81.62 Percentage of Reduction Standard Deviation 7.55	14.33 Percentage of Reduction Standard Deviation 9.05	42.77 Percentage of Reduction Standard Deviation 20.78	50.70 Percentage of Reduction Standard Deviation 9.35	74.47 Percentage of Reduction Standard Deviation 6.56

PRIMARY outcome

Timeframe: Baseline

The pharmacodynamic effect of botulinum toxin type B (E2014) was evaluated based on the inhibition of EDB M-wave amplitude induced by stimulation of the deep peroneal nerve in the left ankles of the study participants. EDB M-wave amplitudes (mV) were measured at screening (baseline).

Outcome measures

Outcome measures
Measure	E2014 (Botulinum Toxin Type B) Placebo- Japanese n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 20 U - Japanese n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 100 U - Japanese n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 500 U - Japanese n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) Placebo - Caucasian n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 20 U - Caucasian n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 100 U - Caucasian n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 500 U - Caucasian n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.
Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline	6.67 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 1.25	4.73 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 1.13	4.95 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 1.48	4.78 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 1.70	7.12 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 1.40	5.48 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 1.92	6.00 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 2.52	5.12 EDB M-Wave Amplitude at Baseline (mV) Standard Deviation 1.15

PRIMARY outcome

Timeframe: Baseline and Up to 12 Weeks

The pharmacodynamic effect of botulinum toxin type B (E2014) was evaluated based on the inhibition of EDB M-wave area induced by stimulation of the deep peroneal nerve in the left ankles of the study participants. EDB M-wave area (mVms) was measured at screening (baseline), and Day 1, Day 2, Day 4, Day 6, Day 8, Day 10, Day 14, Week 4, and Week 12. Rates of EDB M-wave area reduction from baseline were then calculated at each time point. The maximum rates of EDB M-wave area reduction from baseline were presented as a percentage.

Outcome measures

Outcome measures
Measure	E2014 (Botulinum Toxin Type B) Placebo- Japanese n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 20 U - Japanese n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 100 U - Japanese n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) 500 U - Japanese n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese participants.	E2014 (Botulinum Toxin Type B) Placebo - Caucasian n=6 Participants A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 20 U - Caucasian n=6 Participants A single-dose injection solution containing 20 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 100 U - Caucasian n=6 Participants A single-dose injection solution containing 100 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.	E2014 (Botulinum Toxin Type B) 500 U - Caucasian n=6 Participants A single-dose injection solution containing 500 U/ 0.2 mL of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Caucasian participants.
Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline	13.13 Percentage of Reduction Standard Deviation 17.19	43.22 Percentage of Reduction Standard Deviation 15.50	74.97 Percentage of Reduction Standard Deviation 7.60	79.03 Percentage of Reduction Standard Deviation 8.85	14.98 Percentage of Reduction Standard Deviation 12.06	45.65 Percentage of Reduction Standard Deviation 20.34	48.12 Percentage of Reduction Standard Deviation 11.09	75.65 Percentage of Reduction Standard Deviation 4.72

PRIMARY outcome

Timeframe: Baseline

The pharmacodynamic effect of botulinum toxin type B (E2014) was evaluated based on the inhibition of EDB M-wave area induced by stimulation of the deep peroneal nerve in the left ankles of the study participants. EDB M-wave area (mVms) was measured at screening (baseline).