Two Phase 3, randomized, multi-center, double-blind, placebo-controlled studies of the treatment of cervical dystonia were conducted (Study 1 and Study 2). Both studies enrolled only adult patients who had a history of receiving botulinum toxin type A in an open-label manner, with a perceived good response and tolerable adverse effects. Study 1 enrolled patients who were perceived as having an acceptable response to type A toxin, while Study 2 enrolled only patients who had secondarily lost responsiveness to type A toxin. Other eligibility criteria common to both studies were that all patients had moderate or greater severity of cervical dystonia with at least 2 muscles involved, no neck contractures or other causes of decreased neck range of motion, and no history of any other neuromuscular disorder. Patients in Study 1 were randomized to receive placebo, MYOBLOC 5,000 Units or MYOBLOC 10,000 Units. Patients in Study 2 were randomized to receive placebo or 10,000 Units of MYOBLOC. The study agent was administered to subjects in a single treatment session by investigators who selected 2 to 4 muscles per subject from the following: splenius capitis, sternocleidomastoid, levator scapulae, trapezius, semispinalis capitis, and scalene muscles. The total dose was divided between the selected muscles, and from 1 to 5 injections were made per muscle. There were 109 patients enrolled into Study 1, and 77 into Study 2. Patient evaluations continued for 16 weeks post injection.

The primary efficacy outcome variable for both studies was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total Score (scale range of possible scores is 0–87) at Week 4. TWSTRS is comprised of three sub-scales which examine 1) Severity—the severity of the patient's abnormal head position; 2) Pain—the severity and duration of pain due to the dystonia; and 3) Disability— the effects of the abnormal head position and pain on a patient's activities. The secondary endpoints were the Patient Global and Physician Global Assessments of change at Week 4. Both Global Assessments used a 100-point visual-analog scale (VAS). The Patient Global Assessment allows patients to indicate how they feel at the time of their evaluation compared to the pre-injection baseline. Likewise, the Physician Global Assessment indicates the physician's assessment of a patient's change from baseline to Week 4. Scores of 50 indicate no change, 0 much worse, and 100 much better. Results of comparisons of the primary and secondary efficacy variables are summarized in Table 4.

There were no statistically significant differences in results between the 5,000 Unit and 10,000 Unit doses in Study 1. Exploratory analyses of these two studies suggested that the majority of patients who showed a beneficial response by Week 4 had returned to their baseline status between Weeks 12 to 16 post injection. Although there was a MYOBLOC-associated decrease in pain, there remained many patients who experienced an increase in dystonia-related neck pain irrespective of treatment group [ See Adverse Reactions, (6.1)] . TWSTRS Total Score at Week 4 and Patient Global Assessment among subgroups by gender or age showed consistent treatment-associated effects across these subgroups [see Use in Specific Populations (8.5)].  There were too few non-Caucasian patients enrolled to draw any conclusions regarding relative efficacy in racial subsets. 

MYOBLOC was studied in two Phase 2 dose-ranging studies, Studies 3 and 4, which preceded the Phase 3 studies. Studies 3 and 4 had a study design similar to the Phase 3 studies, including eligibility criteria. Study 3 enrolled 85 patients randomized to placebo, MYOBLOC 400 Units, MYOBLOC 1,200 Units, or MYOBLOC 2,400 Units (21 or 22 patients per group). Study 4 enrolled 122 patients randomized to placebo, MYOBLOC 2,500 Units, MYOBLOC 5,000 Units, or MYOBLOC 10,000 Units (30 or 31 patients per group). These studies demonstrated efficacy on the TWSTRS-Total, baseline to Week 4, at doses of 2,400 Units; 2,500 Units; 5,000 Units; and 10,000 Units. Study 3 showed mean improvement from baseline on the Week 4 TWSTRS for placebo and 2,400 Units of 2.0 and 8.5 points respectively (from baselines of 42.0 and 42.4 points). Study 4 showed mean improvement from baseline to Week 4 for placebo, MYOBLOC 2,500 Units, MYOBLOC 5,000 Units, and MYOBLOC 10,000 Units of 3.3, 11.6, 12.5, and 16.4 points, respectively (from baseline of 45.5, 45.6, 45.2, and 47.5 points). Study 3 also showed less response for doses below 2,400 Units.

Study 5 was an open-label, intrapatient dose-escalation study of 3 treatment sessions where each patient with cervical dystonia sequentially received 10,000 Units; 12,500 Units; and 15,000 Units of MYOBLOC, at periods of 12 to 16 weeks between treatment sessions irrespective of their response to their previous dose. This study enrolled 145 patients, of whom 125 received all three treatments. Although this was an open-label design where investigators and patients knew the dose at each treatment session, there were similar mean improvements on the TWSTRS-Total, from baseline to Week 4, for all three doses.

In the MYOBLOC-treated patients (n=112) of the Phase 3 studies, 19% had 2 muscles injected, 48% had 3 muscles injected, and 33% had 4 muscles injected. Table 5 indicates the frequency of use for each of the permitted muscles, and the fraction of the total dose of the treatment injected into each muscle, for those patients in whom the muscle was injected.