Clinical trial NCT01960842: A Study to Assess the Efficacy, Safety and Tolerability of ABT-SLV187 Monotherapy in Subjects With Advanced Parkinson's Disease (PD) and Persistent Motor Complications, Despite Optimized Treatment With Available Anti-Parkinsonian Medications
Official title: An Open-Label, Single-Arm, Baseline-Controlled, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of ABT-SLV187 Monotherapy in Subjects With Advanced Parkinson's Disease and Persistent Motor-Complications Despite Optimized Treatment With Available Anti-Parkinsonian Medication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Parkinson's Disease
Keywords: levodopa
Advanced Parkinson's Disease
carbidopa
levodopa-carbidopa intestinal gel
Safety and Efficacy
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2013-10-11
Enrollment: 31
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to measure the efficacy of ABT-SLV187 in subjects with advanced Parkinson's disease.

Detailed description: The study was composed of a screening period followed by 2 sequential on-treatment periods, as follows:

* Screening Period (up to 28 days): determination of eligibility and discontinuation of antiparkinsonian disease medications other than levodopa-carbidopa immediate release (LC-oral) prior to nasojejunal (N-J) tube placement.
* N-J Test Period (2 to 14 days): first hospitalization period, Baseline assessments, placement of N-J tube, and optimization of levodopa-carbidopa intestinal gel (LCIG) treatment via N-J tube and infusion pump (participant was hospitalized for N-J tube placement but hospitalization was not required for entire duration of LCIG treatment optimization).
* PEG-J Period (12 weeks): second hospitalization period; placement of PEG-J tube; further optimization of LCIG treatment.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria.
2. Subjects have 4 or 5 in modified Hohn and Yahr (H \& Y) classification of disease severity at "Off" state determined by the UPDRS Part V at Screening Visit 1.
3. The subject's advanced Parkinson's disease must be levodopa-responsive as judged by the Investigator.
4. Subjects have had optimal treatment with available Parkinson's disease medication as defined by local standards of care and, based upon the judgment of the Investigator, and their symptoms are judged inadequately controlled on this optimized treatment. Optimized treatment is defined as the maximum therapeutic effect obtained with available anti-parkinsonian pharmacological therapy when no further improvement is expected regardless of any additional manipulations of levodopa and/or other anti parkinsonian medication; this will be based on the Investigator's best clinical judgment.
5. Presence of a recognizable "Off" and "On" state (motor fluctuations) as confirmed by UPDRS Part III (in both "On" and "Off" states), and by the Parkinson's Disease Diary© which must be observed and confirmed at Screening Visit 1.
6. Subjects must be experiencing a minimum of 3 hours per day of "Off" time, as estimated by the Investigator and supported by the UPDRS at Screening Visit 1 and the Parkinson's Disease Diaries at baseline. The "Off" time must occur during a continuous 16-hour interval, including the portion of the day during which the subject is awake the majority of the time (e.g., 5 AM to 9 PM, 7 AM to 11 PM).

Exclusion Criteria:

1. Parkinson's disease diagnosis is unclear or a suspicion of other parkinsonian syndromes exists, such as secondary Parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), Parkinson's-plus syndromes (e.g., multiple system atrophy, progressive supranuclear palsy) or the other neurodegenerative diseases that might mimic the symptoms of Parkinson's disease .
2. Subjects who have undergone neurosurgery for the treatment of Parkinson's disease .
3. Current primary psychiatric diagnosis of acute psychotic disorder or other uncontrolled primary psychiatric diagnoses, (e.g., bipolar disorder or major depressive disorder per Diagnostic and Statistical Manual of Mental Disorders 4th edition, Text Revision (DSM-IV-TR) criteria.
4. Alzheimer's disease; or other significant cognitive impairment or dementia (defined as Mini-Mental State Examination (MMSE) total score \< 24).
5. Subject has significant current suicidal ideation within the previous year as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening or any history of suicide attempts.
6. A low B12 level or low-normal B12 level (less than 300 pg/mL) with elevated methylmalonic acid (MMA). Note: Abnormal Vitamin B12 of questionable clinical significance (i.e., indeterminate or low normal results) prior to or at Screening Visit 2 require appropriate interpretation in conjunction with MMA and homocysteine laboratory values prior to proceeding further into the study.

Primary outcomes:
measure: Average Daily Normalized "Off" Time: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
Secondary outcomes:
measure: Average Daily Normalized "On" Time Without Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Parkinson's Disease Questionnaire (PDQ-39) Summary Index: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Clinical Global Impression - Change (CGI-I) Score at the Final PEG-J Visit
timeFrame: Final PEG-J Visit (up to week 12)
measure: Patient Global Impression of Change (PGI-C) Score at the Final PEG-J Visit
timeFrame: Final PEG-J Visit (up to week 12)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part IIl Score: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Average Daily Normalized "On" Time With Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Parkinson's Disease Questionnaire (PDQ-39) Mobility, Emotional Well-Being, Stigma, Social Support, Cognition, Communication, and Bodily Discomfort Domain Scores: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Total Score: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline and Final PEG-J Visit (up to Week 12)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Part IV Score: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Average Daily Normalized "Off" Time Excluding Subjects Who Did Not Receive LCIG During the Entire PEG-J Period: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Average Daily Normalized "Off" Time Including All PD Diaries Regardless if They Were Completed After the Subject Had Used a Concomitant Anti-Parkinsonian Medication: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Final PEG-J Visit (up to week 12)
measure: Average Daily Normalized "Off" Time at Baseline and Each Visit: Change From Baseline To The Final PEG-J Visit
timeFrame: Baseline (end of screening period) and Weeks 2, 4, 6, 8, 10, and 12
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From N-J placement to the end of study or early termination of treatment, including the removal of PEG-J (up to 17 weeks), plus 30 days.
measure: Number of Participants With Potentially Clinically Significant Vital Sign Parameters
timeFrame: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
measure: Number of Participants With Potentially Clinically Significant Values for Hematology Parameters
timeFrame: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
measure: Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters
timeFrame: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
measure: Number of Participants With Potentially Clinically Significant Values for 12-lead Electrocardiogram (ECG)
timeFrame: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
Other outcomes:
measure: Neurological Examination
timeFrame: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
measure: Physical Examination
timeFrame: From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)
Locations:
Study officials:
affiliation: AbbVie Japan
name: Masayoshi Yanagawa, PhD
role: STUDY_DIRECTOR
References:
citation: Murata M, Mihara M, Hasegawa K, Jeon B, Tsai CH, Nishikawa N, Oeda T, Yokoyama M, Robieson WZ, Ryman D, Eaton S, Chatamra K, Benesh J. Efficacy and safety of levodopa-carbidopa intestinal gel from a study in Japanese, Taiwanese, and Korean advanced Parkinson's disease patients. NPJ Parkinsons Dis. 2016 Nov 3;2:16020. doi: 10.1038/npjparkd.2016.20. eCollection 2016.