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

NCT ID: NCT01960842

Last Updated: 2018-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-03-31

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.

Conditions

Advanced Parkinson's Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Levodopa-Carbidopa Intestinal Gel (LCIG)

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).

Group Type: EXPERIMENTAL

Levodopa-carbidopa intestinal gel

Intervention Type: 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)

CADD-Legacy® 1400 ambulatory infusion pump

Intervention Type: DEVICE

PEG tube

Intervention Type: DEVICE

percutaneous endoscopic gastrostomy tube

J-tube

Intervention Type: DEVICE

jejunal tube

Interventions

Levodopa-carbidopa intestinal gel

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)

Intervention Type: DRUG

CADD-Legacy® 1400 ambulatory infusion pump

Intervention Type: DEVICE

PEG tube

percutaneous endoscopic gastrostomy tube

Intervention Type: DEVICE

J-tube

jejunal tube

Intervention Type: DEVICE

Other Intervention Names

ABT-SLV187; LCIG

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.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Masayoshi Yanagawa, PhD

Role: STUDY_DIRECTOR

AbbVie Japan

References

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.

Reference Type: RESULT

PMID: 28725701 (View on PubMed)

Related Links

http://rxabbvie.com

Related Info

Other Identifiers

M12-921

Identifier Type: -

Identifier Source: org_study_id