Clinical trial NCT02610868: Open-Label and Single-Arm Study of MYOBLOC® in the Treatment of Troublesome Sialorrhea in Adults
Official title: A Phase 3, Long-Term, Open-Label and Single-Arm Study of MYOBLOC® in the Treatment of Troublesome Sialorrhea in Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sialorrhea
Keywords: Cerebral Palsy
ALS
Stroke
Neuroleptics
Lead sponsor: Supernus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-11-20
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Multicenter, open-label, outpatient study of the safety and effectiveness of repeated doses of MYOBLOC over a 1-year duration in adult subjects with troublesome sialorrhea.

Detailed description: Multicenter, open-label, outpatient study of the safety and effectiveness of repeated doses of MYOBLOC over a 1-year duration in adult subjects with troublesome sialorrhea. The primary goal is to determine the long-term safety and tolerability of MYOBLOC (administered intraglandularly as single total dose of 3,500 Units) treatments every 13 weeks over a maximum possible duration of 1 year in adult subjects with troublesome sialorrhea. The secondary goal is to assess the magnitude of therapeutic response of MYOBLOC (administered intraglandularly as a single total dose of 3,500 Units) using effectiveness assessments performed at intervals after treatments every 13 weeks over a maximum possible duration of 1 year.

Eligibility criteria: Inclusion Criteria:

* Seeking treatment for troublesome sialorrhea for at least 3 months that is occurring secondary to any disorder or related to any cause, including, but not limited to, Parkinson's Disease (PD), adult cerebral palsy, amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, oral cancer, and side effects of other medications.
* Able to read and provide written informed consent before enrollment into the study, or the subject's caregiver (Legally Authorized Representative) can provide written informed consent.
* Male or female, 18 to 85 years of age (inclusive).
* Minimum unstimulated salivary flow rate of 0.2 g/min at screening
* Minimum Investigator's Drooling Frequency and Severity Scale (DFSS) score of 4 at screening.
* Ability and availability to participate in the study for up to 1 year (ALS subjects: ability and availability to participate in the study for at least 6 months), based on overall health of the subject and disease prognosis

Exclusion Criteria:

* A moderate to high risk of aspiration will exclude participation in this study. Subjects whose risk of aspiration are judged by the Investigator to be satisfactorily controlled by placement of PEG tube or G-tube for nutritional support are eligible to participate.
* Respiratory forced vital capacity (FVC) of \<20% of predicted
* Prior botulinum toxin type A or B treatment in the salivary gland(s) identified for treatment in this study within 24 weeks before screening. Prior botulinum toxin type A or B treatment into other anatomical regions not selected for treatment in this study is not exclusionary, but must have occurred at least 12 weeks before screening
* Subjects should be excluded if, in the Investigator's opinion, the subject failed to respond to previous treatment with botulinum toxin. Subjects should not receive nor have any plans for receiving any botulinum toxin treatment, other than the study drug (MYOBLOC), during the entire course of the study (from the point the informed consent is signed until subject's participation is complete).
* Concomitant use, or exposure within 5 half-lives of screening, of aminoglycoside antibiotics, curare-like agents, or other agents that interfere with neuromuscular function
* Prior salivary gland surgery
* Current treatment or treatment at any time during the study with Coumadin® (warfarin) or similar anti-coagulant medications. Anti-platelet medications are not specifically exclusionary
* Evidence of any clinically significant neurologic disease
* Pregnancy or lactation
* Anticipated or scheduled surgery during the study period. A PEG tube/G tube may be placed for nutritional support at any time during the study and will not exclude the subject from continued study participation.
* Major surgery (requiring general anesthesia, except PEG tube/G tube placement ) within the previous 6 months before screening.
* Current infection at the sialorrhea treatment injection site(s)
* History of drug or alcohol abuse currently or within the previous 6 months
* Participation in another clinical drug, device, or biological agent study within 30 days of screening or while participating in this study

Primary outcomes:
measure: Occurrence, Seriousness, Severity, and Causality Assessment of Treatment Emergent Adverse Events (TEAE)
timeFrame: Visits at Weeks 4 and 13 combined for each TS; including Visit at Week 8 for TS1
measure: Occurrence of Adverse Events of Special Interest (AESI)
timeFrame: Visits at Weeks 4 and 13 combined for each TS; including Visit at Week 8 for TS1
measure: Columbia Suicide Rating Scale (C-SSRS): Suicidal Ideation, Behavior Scores and Intensity Scores
timeFrame: Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Occurrence of Dental Adverse Events
timeFrame: Visits at Weeks 4 and 13 combined for each TS; including Visit at Week 8 for TS1
Secondary outcomes:
measure: Change From Baseline in Unstimulated Salivary Flow Rate (USFR): Treatment Sessions 1-4
timeFrame: Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Change From Baseline in Clinical Global Impression of Severity (CGI-S)
timeFrame: Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Clinical Global Impression of Change (CGI-C)
timeFrame: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Change From Baseline in Drooling Frequency and Severity Scale Performed by Trained Assessor (DFSS-I)
timeFrame: Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Change From Baseline in Drooling Frequency and Severity Scale Performed by Subject (DFSS-S)
timeFrame: Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Change From Baseline in Patient Global Impression of Severity (PGI-S)
timeFrame: Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Patient Global Impression of Change (PGI-C)
timeFrame: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
measure: Change From Baseline in Drooling Impact Score (DIS)
timeFrame: Baseline (Day 1) of each TS to the following: TS1 Visits at Weeks 4, 8, 13; TS2-4 Visits at Weeks 4, 13
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Loma Linda
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Atlantis
country: United States
state: Florida
city: Boca Raton
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Port Charlotte
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Kansas City
country: United States
state: Kansas
city: Overland Park
country: United States
state: Kansas
city: Elkridge
country: United States
state: Maryland
city: Farmington Hills
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Edison
country: United States
state: New Jersey
city: Centerville
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Greenville
country: United States
state: South Carolina
city: Cordova
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
city: Kirkland
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Grodno
country: Belarus
city: Dnipropetrovsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Rivne
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Zaporizhzhya
country: Ukraine
Study officials:
affiliation: Supernus Pharmaceuticals, Inc.
name: Najeebah Abdul-Musawir, MD,MBA
role: STUDY_DIRECTOR
References: