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

NCT01960842 | Completed Phase 3 Results

• 1 other identifier: M12-921
• Study Type: interventional
• Target: 31
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Advanced Parkinson's Disease

Keywords

levodopa; Advanced Parkinson's Disease; carbidopa; levodopa-carbidopa intestinal gel; Safety and Efficacy

Outcome Measures

Primary Outcomes (1)

• Average Daily Normalized "Off" Time: Change From Baseline To The Final PEG-J Visit

  Based on the Parkinson's Disease Symptom Diary. "On" time is when PD symptoms are well controlled by the drug. "Off" time is when PD symptoms are not adequately controlled by the drug. The diary is completed every 30 minutes for the full 24 hours of each of 3 days prior to selected clinic visits. It reflects both time awake and time asleep. Daily totals are normalized to a 16-hour scale (i.e. 16 hours of awake time). The normalized totals for the 3 days prior to the visit are averaged for the analysis. Negative change from baseline for "off" time indicates improvement.

  Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Secondary Outcomes (19)

• Average Daily Normalized "On" Time Without Troublesome Dyskinesia: Change From Baseline To The Final PEG-J Visit

  Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

• Parkinson's Disease Questionnaire (PDQ-39) Summary Index: Change From Baseline To The Final PEG-J Visit

  Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

• Clinical Global Impression - Change (CGI-I) Score at the Final PEG-J Visit

  Final PEG-J Visit (up to week 12)

• Patient Global Impression of Change (PGI-C) Score at the Final PEG-J Visit

  Final PEG-J Visit (up to week 12)

• Unified Parkinson's Disease Rating Scale (UPDRS) Part II Score: Change From Baseline To The Final PEG-J Visit

  Baseline (end of screening period) and Final PEG-J Visit (up to week 12)

Other Outcomes (2)

• Neurological Examination

  From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

• Physical Examination

  From Baseline (end of screening period) to Final PEG-J Visit (up to week 12)

Study Arms (1)

Levodopa-Carbidopa Intestinal Gel (LCIG)

EXPERIMENTAL

All participants received LCIG via the N-J tube during the nasojejunal (N-J) Test Period and delivered to the proximal small intestine via percutaneous endoscopic gastrostomy - with jejunal extension tube (PEG-J) during the Post-PEG-J Long-Term Treatment Period. The starting dose was individually determined based on the daily dose of oral levodopa prior to study enrollment. The infusion dose was individually optimized for each participant on the basis of response and potential adverse events. During the PEG-J Period, LCIG was expected to be infused continuously over approximately 16 hours daily with a rate of infusion ranging from 1 to 10 mL/hour (20 to 200 mg of levodopa/hour).

Drug: Levodopa-carbidopa intestinal gel; Device: CADD-Legacy® 1400 ambulatory infusion pump; Device: PEG tube; Device: J-tube

Interventions

Levodopa-carbidopa intestinal gel DRUG

Dose levels will be individually optimized. Infusion should be kept within a range of 0.5-10 mL/hour (10-200 mg levodopa/hour) and is usually 2-6 mL/hour (40-120 mg levodopa/hour)

Also known as: ABT-SLV187, LCIG

Levodopa-Carbidopa Intestinal Gel (LCIG)

CADD-Legacy® 1400 ambulatory infusion pump DEVICE

Levodopa-Carbidopa Intestinal Gel (LCIG)

PEG tube DEVICE

percutaneous endoscopic gastrostomy tube

Levodopa-Carbidopa Intestinal Gel (LCIG)

J-tube DEVICE

jejunal tube

Levodopa-Carbidopa Intestinal Gel (LCIG)

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of idiopathic Parkinson's disease according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria.
• 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.
• The subject's advanced Parkinson's disease must be levodopa-responsive as judged by the Investigator.
• 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.
• 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.
• 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).

You may not qualify if:

• 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 .
• Subjects who have undergone neurosurgery for the treatment of Parkinson's disease .
• 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.
• Alzheimer's disease; or other significant cognitive impairment or dementia (defined as Mini-Mental State Examination (MMSE) total score \< 24).
• 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.
• 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.

Sponsors & Collaborators

• AbbVie: lead

Related Publications (1)

• 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.

  PMID: 28725701 RESULT

Related Links

• Related Info

MeSH Terms

Interventions

Jejunostomy

Intervention Hierarchy (Ancestors)

Enterostomy; Digestive System Surgical Procedures; Surgical Procedures, Operative; Ostomy

Results Point of Contact

• Title: Global Medical Information
• Organization: AbbVie

1-800-633-9110

Study Officials

• Masayoshi Yanagawa, PhD

  AbbVie Japan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2013
• First Posted: October 11, 2013
• Study Start: October 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 30, 2018
• Results First Posted: April 20, 2016

Record last verified: 2016-04