Randomized, Double-Blind, Placebo-Controlled, Parallel, Group Dose-Response, Study of E2014 in Patients WIth Spasmodic Torticollis
Condition: Cervical Dystonia; Spasmodic Torticollis
MeSH terms: Dystonia; Torticollis
Intervention: BOTULINUM TOXIN TYPE B
Intervention MeSH terms: rimabotulinumtoxinB; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 133.0
Sex: All
Minimum age: 20 Years
Maximum age: 74 Years

Summary:

      To evaluate efficacy and safety of E2014 (2500U, 5000U, 10000U, placebo) in a multicenter,
      randomized, double-blind, parallel group comparative study by intramuscularly administering
      to patients with spasmodic torticollis. Primary endpoint for efficacy evaluation is changes
      in TWSTRS total scores from baseline measured at Week 4 and the clinical recommended dose
      will be examined with Williams multiple comparison. For safety evaluation, an inter group
      comparison (active drug and placebo) will be performed mainly focusing on incidence of
      adverse events, adverse drug reactions, and abnormal changes in laboratory parameters.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients who can give written informed consent and aged between greater than or equal
             to 20 years and less than 75 years at the time of obtaining prior consent
             (irrespective of gender).

          -  Patients with dystonic symptoms at least 2 or more lesions in the following cervical
             muscles.

          -  Sternocleidomastoid

          -  Scalenus complex (scalenus anterior, scalenus medius, and scalenus posterior)

          -  Trapezius

          -  Levator scapulae

          -  Splenius capitis

          -  Semispinalis capitis

          -  Patients who persistently have symptoms in the above (2) for 1 year or longer.

          -  Patients weighing greater than or equal to 40 kg.

          -  Patients whose TWSTRS total score at baseline is greater than or equal to 20.

          -  Patients whose TWSTRS-severity score at baseline is greater than or equal to 10.

          -  Patients whose TWSTRS-disability score at baseline is greater than or equal to 3.

          -  Patients whose TWSTRS-pain score at baseline is greater than or equal to 1.

          -  Patients who are judged to be eligible for study entry by the investigator or
             subinvestigator based on their physical and neurological findings, laboratory
             parameters, and ECG results.

        Exclusion Criteria:

          -  Patients who are botulinum toxin-resistant in previous exposures (primary
             no-responder*)

             *If patients who were once responder to botulinum toxin treatment but thereafter
             became non-responder can be included in this study.

          -  Patients whose passive range of motion in the neck is significantly narrowed due to
             cervical contracture or spondylosis.

          -  Patients having only pure retrocollis- or anterocollis-associated symptoms.

          -  Patients who received botulinum toxin agents within 4 months prior to study treatment
             of E2014, or those who show carry-over effect of previous treatment with botulinum
             toxin at the time of starting study administration even though the previous treatment
             was given 4 months or earlier.

          -  Patients who were treated with narcotics or antibiotics that may potentiate effects of
             muscle relaxation (spectinomycin hydrochloride preparations, aminoglycosides,
             polypeptides, tetracyclines, lincomycins) within 4 months prior to study treatment.

          -  Patients who started or altered the dose levels of the following agents
             (musculoskeletal relaxants, antispasm drugs, strong tranquilizers, benzodiazepines
             including similar drugs, anticholinergic drugs, antiparkinsonian drugs,
             antidepressants) within 4 weeks prior to study treatment.

          -  Patients who received medical care(s) other than pharmacotherapies (surgical
             interventions, MAB, acupuncture, relaxation, etc.) prior to study treatment showing
             carry-over effect of these cares or unstable condition at the time of starting study
             treatment.

          -  Patients who have a history of myectomy or neurectomy in the neck and/or shoulder.

          -  Patients who have a history of hypersensitivity to E2014's ingredients (botulinum
             toxin type B, human serum albumin, sodium succinate buffer solution), or other type of
             botulinum toxins.

          -  Patients with complication(s) or history of serious neurological or musculoskeletal
             disease (myasthenia, amyotrophic lateral sclerosis, etc.), cardiovascular disease
             (acute myocardial infarction, etc.), respiratory disease (COPD, etc.), renal disease
             (acute or chronic renal failure, etc.), hepatic disease (cirrhosis, etc.),
             gastrointestinal disease (paralytic ileus, etc.), dermatological disease (toxic
             epidermal necrosis, etc.), psychiatric disease (schizophrenia, alcohol or drug
             dependence, etc.), hematological disease (aplastic anemia, etc.), and/or infectious
             disease (hepatitis, syphilis, AIDS, etc.).

          -  Patients with complication or history of malignant tumor(s).

          -  Patients who participated in another clinical study within 30 days prior to obtaining
             informed consent for this study.

          -  Women of pregnant, childbearing potential, childbearing intension during the study
             period, or lactating.

          -  Others who are judged to be ineligible for study entry by the investigator or
             subinvestigator