Spasmodic Torticollis
Conditions
Brief summary
To evaluate inter-ethnic similarity in pharmacodynamics between Japanese and Caucasian healthy adult male subjects by comparing electrophysiological reactions after administering E2014 to extensor digitorum brevis muscle (EDB).
Interventions
DRUGE2014 (Botulinum toxin type B)
A single-dose injection solution containing 20 units (U), 100 U, or 500 U/ 0.2 milliliters (mL) of E2014 was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese and Caucasian participants. Duration of treatment lasted for 12 weeks: from Day -1 to Week 12. Participants were hospitalized from a day before study treatment to Day 8 for 9 nights and 10 days, and visited at the medical institution on Days 10 and 14, and Weeks 4 and 12.
DRUGE2014 (Botulinum toxin type B) Placebo
A single-dose injection solution of E2014 Placebo was administered to extensor digitorum brevis (EDB) muscle in the left lower limb to Japanese and Caucasian participants. Duration of treatment lasted for 12 weeks: from Day -1 to Week 12. Participants were hospitalized from a day before study treatment to Day 8 for 9 nights and 10 days, and visited at the medical institution on Days 10 and 14, and Weeks 4 and 12.
Sponsors
Eisai Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
MALE
Age
20 Years to 44 Years
Healthy volunteers
No
Inclusion criteria
1. Participants aged between 20 and 44 years at the time of obtaining informed consent. 2. Participants whose M wave amplitude potential (between baseline and negative peak) in the EDB by stimulating peroneal nerve in the foot joints is 1 mV or more during electrophysiological examinations at the times of screening and immediately before administration. 3. Participants who are judged to be eligible for study entry by an investigator or subinvestigator at screening and at immediately before pre-treatment medical examination. 4. Participants who are given a full explanation about the objective and details of this study before starting screening and give written consent based on their free will.
Exclusion criteria
1. Participants who have a complication or history of peripheral neuropathy, nerve root impairment, muscle disease. 2. Participants with a disease that may influence the study drug evaluation, such as disorders of the gastrointestinal tract, liver, respiratory, endocrine, hematological, neurological, psychiatric and cardiovascular system, and congenital abnormality in metabolism. 3. Participants who have accessory deep peroneal nerve. 4. Participants who previously received a treatment with botulinum toxin. 5. Participants with a history of hypersensitivity to any component of E2014 (human serum albumin, succinate buffer solution). 6. Participants who are positive for urine drug screening at the time of screening or immediately before study drug administration. 7. Participants who received prescription drug(s) within 1 month before study drug administration. 8. Participants who have been treated with another investigational drug within 4 months before study drug administration. 9. Participants who have experienced heavy exercise or hard labor within 2 weeks before study drug administration. 10. Participants who underwent blood transfusion within 3 months before, those whose 400 mL of whole blood was collected within 3 months before, or those whose 200 mL of whole blood was collected within 1 month before study drug administration. 11. Participants who are positive for hepatitis B surface antigen (HBs antigen), hepatitis C virus (HCV) antibody, or serologic test for syphilis (STS). 12. Participants who received a diagnosis of acquired immunodeficiency syndrome (AIDS) or those with positive result for human immunodeficiency virus. 13. Participants who are unwilling or unable to abide by the requirements of this study, or those who may violate the prohibitions and restrictions of this study. 14. Participants who are judge to be ineligible for study entry by a principal investigator or subinvestigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 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. |
| Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 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). |
| Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 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. |
| Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 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). |
Countries
Japan
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| Total | 48 |
Baseline characteristics
| Characteristic | Total | E2014 (Botulinum Toxin Type B) Placebo- Japanese | E2014 (Botulinum Toxin Type B) 20 U - Japanese | E2014 (Botulinum Toxin Type B) 100 U - Japanese | E2014 (Botulinum Toxin Type B) 500 U - Japanese | E2014 (Botulinum Toxin Type B) Placebo - Caucasian | E2014 (Botulinum Toxin Type B) 20 U - Caucasian | E2014 (Botulinum Toxin Type B) 100 U - Caucasian | E2014 (Botulinum Toxin Type B) 500 U - Caucasian |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 28.3 years STANDARD_DEVIATION 5.7 | 22.7 years STANDARD_DEVIATION 2.9 | 28.0 years STANDARD_DEVIATION 5.4 | 23.3 years STANDARD_DEVIATION 2.9 | 22.2 years STANDARD_DEVIATION 2.6 | 33.7 years STANDARD_DEVIATION 2.7 | 34.5 years STANDARD_DEVIATION 3.7 | 32.7 years STANDARD_DEVIATION 2.9 | 29.3 years STANDARD_DEVIATION 2.6 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 48 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 2 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at 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).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E2014 (Botulinum Toxin Type B) Placebo- Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 6.67 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 1.25 |
| E2014 (Botulinum Toxin Type B) 20 U - Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 4.73 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 1.13 |
| E2014 (Botulinum Toxin Type B) 100 U - Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 4.95 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 1.48 |
| E2014 (Botulinum Toxin Type B) 500 U - Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 4.78 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 1.7 |
| E2014 (Botulinum Toxin Type B) Placebo - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 7.12 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 1.4 |
| E2014 (Botulinum Toxin Type B) 20 U - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 5.48 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 1.92 |
| E2014 (Botulinum Toxin Type B) 100 U - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 6.00 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 2.52 |
| E2014 (Botulinum Toxin Type B) 500 U - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude at Baseline | 5.12 EDB M-Wave Amplitude at Baseline (mV) | Standard Deviation 1.15 |
Primary
Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At 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).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E2014 (Botulinum Toxin Type B) Placebo- Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 18.90 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 4.23 |
| E2014 (Botulinum Toxin Type B) 20 U - Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 14.97 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 3.8 |
| E2014 (Botulinum Toxin Type B) 100 U - Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 14.38 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 4.67 |
| E2014 (Botulinum Toxin Type B) 500 U - Japanese | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 14.85 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 4.78 |
| E2014 (Botulinum Toxin Type B) Placebo - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 18.68 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 1.99 |
| E2014 (Botulinum Toxin Type B) 20 U - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 16.18 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 4.03 |
| E2014 (Botulinum Toxin Type B) 100 U - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 17.57 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 5.67 |
| E2014 (Botulinum Toxin Type B) 500 U - Caucasian | Extensor Digitorum Brevis (EDB) Muscle M-Wave Area At Baseline | 14.58 EDB M-Wave Area at Baseline (mVms) | Standard Deviation 2.09 |
Primary
Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From 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), 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.
Time frame: Baseline and Up to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E2014 (Botulinum Toxin Type B) Placebo- Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 9.02 Percentage of Reduction | Standard Deviation 13.51 |
| E2014 (Botulinum Toxin Type B) 20 U - Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 48.53 Percentage of Reduction | Standard Deviation 16.98 |
| E2014 (Botulinum Toxin Type B) 100 U - Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 70.95 Percentage of Reduction | Standard Deviation 6.12 |
| E2014 (Botulinum Toxin Type B) 500 U - Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 81.62 Percentage of Reduction | Standard Deviation 7.55 |
| E2014 (Botulinum Toxin Type B) Placebo - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 14.33 Percentage of Reduction | Standard Deviation 9.05 |
| E2014 (Botulinum Toxin Type B) 20 U - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 42.77 Percentage of Reduction | Standard Deviation 20.78 |
| E2014 (Botulinum Toxin Type B) 100 U - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 50.70 Percentage of Reduction | Standard Deviation 9.35 |
| E2014 (Botulinum Toxin Type B) 500 U - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Amplitude Reduction From Baseline | 74.47 Percentage of Reduction | Standard Deviation 6.56 |
Primary
Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From 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), 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.
Time frame: Baseline and Up to 12 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| E2014 (Botulinum Toxin Type B) Placebo- Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 13.13 Percentage of Reduction | Standard Deviation 17.19 |
| E2014 (Botulinum Toxin Type B) 20 U - Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 43.22 Percentage of Reduction | Standard Deviation 15.5 |
| E2014 (Botulinum Toxin Type B) 100 U - Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 74.97 Percentage of Reduction | Standard Deviation 7.6 |
| E2014 (Botulinum Toxin Type B) 500 U - Japanese | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 79.03 Percentage of Reduction | Standard Deviation 8.85 |
| E2014 (Botulinum Toxin Type B) Placebo - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 14.98 Percentage of Reduction | Standard Deviation 12.06 |
| E2014 (Botulinum Toxin Type B) 20 U - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 45.65 Percentage of Reduction | Standard Deviation 20.34 |
| E2014 (Botulinum Toxin Type B) 100 U - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 48.12 Percentage of Reduction | Standard Deviation 11.09 |
| E2014 (Botulinum Toxin Type B) 500 U - Caucasian | Maximum Rates of Extensor Digitorum Brevis (EDB) Muscle M-Wave Area Reduction From Baseline | 75.65 Percentage of Reduction | Standard Deviation 4.72 |