Sialorrhea
Conditions
Keywords
Sialorrhea, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), stroke, neuroleptics
Brief summary
This study will evaluate the efficacy and safety of MYOBLOC in the treatment of Sialorrhea (drooling), which can be a symptom of many disease conditions. MYOBLOC will be injected directly into the salivary glands. MYOBLOC has been shown in previous trials to safely decrease saliva production, thereby demonstrating its potential as a safe and effective treatment for troublesome sialorrhea.
Detailed description
Primary Objective: To determine the efficacy of MYOBLOC (administered via intraglandular as a single total dose of 2,500 Units or 3,500 Units) versus placebo in the treatment of troublesome sialorrhea in adult subjects via the assessment of unstimulated salivary flow rate and clinical global impression of sialorrhea severity and improvement at Week 4 post-injection (Part A). It is hypothesized that both MYOBLOC doses will achieve greater efficacy than placebo in relieving sialorrhea at 4 weeks post-injection. To compare the safety and tolerability of MYOBLOC versus placebo over a 13 week post-injection period (Part A). Secondary Objective: To assess the onset and duration of therapeutic response of MYOBLOC using efficacy assessments performed at Weeks 1, 2, 4, 8, and 13 after the first treatment (Part A). To assess the duration of therapeutic response of MYOBLOC (administered via intraglandular as a single total dose of 3,500 Units) using efficacy assessments performed at intervals after treatments every 13 weeks over a maximum possible duration of 65 weeks (Part B). To determine the long-term safety and tolerability of MYOBLOC treatments every 13 weeks over a maximum possible duration of 65 weeks (Part B).
Interventions
DRUGMYOBLOC
MYOBLOC (rimabotulinumtoxinB) Injection, or botulinum toxin type B, is the "B" serotype of botulinum toxin. It is the only commercially available "B" serotype, and also the only available botulinum toxin that does not require reconstitution for use.
OTHERPLACEBO
Sponsors
Solstice Neurosciences, LLC, a subsidiary of US WorldMeds, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Seeking treatment for troublesome sialorrhea for at least 3 months that is occurring secondary to any disorder or related to any cause * Investigator sites will review entire list of inclusion criteria with potential subjects
Exclusion criteria
* Any known prior exposure to botulinum toxin type B, or known adverse reaction or sensitivity to botulinum toxin type A, or known sensitivity to any of the MYOBLOC solution components. * Prior botulinum toxin treatment to the salivary glands at any time * Investigator sites will review entire list of
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unstimulated Salivary Flow Rate (USFR) at Week 4 Post-injection Visit (Part A) | 4 Weeks | Change weight of expectorated saliva at a Week 4 post-injection visit. |
| Clinical Global Impression Change (CGI-C) at Week 4 Post-injection (Part A) | 4 weeks | CGI-C was assessed on a 7-point scale ranging from "very much improved" to "very much worse" with 1 assigned to "very much improved" and 7 assigned to "very much worse"; ranging from a minimum score of 1 and a maximum score of 7. |
Countries
Russia, Ukraine, United States
Contacts
STUDY_DIRECTORJonathan Rubin, MD
Supernus Pharmaceuticals, Inc.
Participant flow
Recruitment details
The study was conducted at 33 sites including United States, Russia and Ukraine.
Pre-assignment details
DB: Double Blind (Part A) OL: Open Label (Part B)
Participants by arm
| Arm | Count |
|---|---|
| MYOBLOC 2500 U Subjects were dosed per treatment assignment of 2500 U MYOBLOC. | 63 |
| MYOBLOC 3500 U Subjects were dosed per treatment assignment of 3500 U MYOBLOC. | 64 |
| PLACEBO Placebo was dosed as an exact match of MYOBLOC. | 57 |
| Total | 184 |
Baseline characteristics
| Characteristic | Total | MYOBLOC 2500 U | MYOBLOC 3500 U | PLACEBO |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 106 Participants | 34 Participants | 39 Participants | 33 Participants |
| Age, Categorical Between 18 and 65 years | 78 Participants | 29 Participants | 25 Participants | 24 Participants |
| Age, Continuous | 63.8 years STANDARD_DEVIATION 13.4 | 62.6 years STANDARD_DEVIATION 13 | 64.6 years STANDARD_DEVIATION 14 | 64.1 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 5 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 176 Participants | 58 Participants | 62 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 175 Participants | 60 Participants | 60 Participants | 55 Participants |
| Sex: Female, Male Female | 40 Participants | 15 Participants | 9 Participants | 16 Participants |
| Sex: Female, Male Male | 144 Participants | 48 Participants | 55 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 63 | 2 / 64 | 1 / 60 | 9 / 170 |
| other Total, other adverse events | 44 / 63 | 38 / 64 | 16 / 60 | 143 / 170 |
| serious Total, serious adverse events | 1 / 63 | 4 / 64 | 4 / 60 | 32 / 170 |
Outcome results
Primary
Clinical Global Impression Change (CGI-C) at Week 4 Post-injection (Part A)
CGI-C was assessed on a 7-point scale ranging from very much improved to very much worse with 1 assigned to very much improved and 7 assigned to very much worse; ranging from a minimum score of 1 and a maximum score of 7.
Time frame: 4 weeks
Population: Per protocol the intent-to-treat population who were injected with study medication and had at least 1 post injection CGI-C measurement up to week 4 (inclusive).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MYOBLOC 2500 U | Clinical Global Impression Change (CGI-C) at Week 4 Post-injection (Part A) | 2.38 score on a scale | Standard Error 0.12 |
| MYOBLOC 3500 U | Clinical Global Impression Change (CGI-C) at Week 4 Post-injection (Part A) | 2.45 score on a scale | Standard Error 0.12 |
| Placebo | Clinical Global Impression Change (CGI-C) at Week 4 Post-injection (Part A) | 3.59 score on a scale | Standard Error 0.13 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Primary
Unstimulated Salivary Flow Rate (USFR) at Week 4 Post-injection Visit (Part A)
Change weight of expectorated saliva at a Week 4 post-injection visit.
Time frame: 4 Weeks
Population: The per protocol included subjects with a minimum USFR of 0.2 g/min.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MYOBLOC 2500 U | Unstimulated Salivary Flow Rate (USFR) at Week 4 Post-injection Visit (Part A) | -0.37 g/minute | Standard Error 0.03 |
| MYOBLOC 3500 U | Unstimulated Salivary Flow Rate (USFR) at Week 4 Post-injection Visit (Part A) | -0.36 g/minute | Standard Error 0.03 |
| Placebo | Unstimulated Salivary Flow Rate (USFR) at Week 4 Post-injection Visit (Part A) | -0.07 g/minute | Standard Error 0.03 |
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA