Safety/Efficacy Study of Levodopa-Carbidopa Intestinal Gel in Parkinson's Subjects

NCT00360568 | Completed Phase 3 Results DMC

• 2 other identifiers: S187.3.0032006-000578-53
• Study Type: interventional
• Target: 62
• Locations: 3 countries
• Sites: 22

Brief Summary

Long term safety and efficacy (12 months) of levodopa-carbidopa intestinal gel.

Conditions

Dyskinesias; Parkinson's Disease; Severe Motor Fluctuations

Keywords

carbidopa; severe motor fluctuations; intestinal gel; levodopa; efficacy; levodopa carbidopa intestinal gel; dyskinesia; Parkinson's Disease; Duodopa; levodopa-carbidopa; DUOPA

Outcome Measures

Primary Outcomes (13)

• Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths and Discontinuations Due to AEs

  AE=any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that: results in death; is life-threatening (an event in which the subject was at risk of death at the time of the event); requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events. Treatment-emergent events (TEAE or TESAE)=those starting after the first dose of study drug. Severe=severity reported as 'severe' or missing. Possibly or Probably Treatment Related=drug-event relationship reported as 'possible', 'probable' or missing. Death=a fatal outcome of an SAE or AE.

  From study enrollment to the end of study or early termination of treatment, including the removal of PEG-J, plus 30 days.

• Number of Participants With Device Complications

  Complications of the infusion device were collected. Pump, intestinal tube, PEG, stoma, and other complications included (but were not limited to) device breakage, device leakage, device malfunction, device misuse, device occlusion, intentional and unintentional device removal by participant, complication of device insertion, device dislocation, device breakage, device dislocation, and device site reaction.

  12 months

• Number of Participants With Potentially Clinically Significant Values for Hematology Parameters

  Terms abbreviated in the table include females (f) and males (m).

  12 months

• Number of Participants With Potentially Clinically Significant Values for Clinical Chemistry Parameters

  Terms abbreviated in the table include upper limit of normal (ULN), male (m), and female (f).

  12 months

• Number of Participants With Potentially Clinically Significant Vital Sign Parameters

  Terms abbreviated in the table include supine systolic blood pressure (SuSBP), standing systolic blood pressure (StSBP), orthostatic systolic blood pressure (OSBP), supine diastolic blood pressure (SuDBP), standing diastolic blood pressure (StDBP), orthostatic diastolic blood pressure (ODBP), supine pulse (SuP) in beats per minute (bpm), standing pulse (StP), and body temperature (Temp). Increase and decrease are signified by ↑ and ↓, respectively.

  12 months

• Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Parameters

  Terms abbreviated in the table include heart rate (HR) in beats per minute (bpm), PR interval (PRI), QT interval corrected for heart rate using Bazett's formula (QTcB), and QT interval corrected for heart rate using Fridericia's formula (QTcF). Increase and decrease are signified by ↑ and ↓, respectively.

  12 months

• Number of Participants With Sleep Attacks at Baseline and Endpoint

  To prospectively monitor for the possible development of sleep attacks, participants were asked if they had experienced any events in which they fell asleep suddenly or unexpectedly, including while engaged in some activity (e.g., eating/drinking, speaking, or driving) or at rest, with or without any previous warning of sleepiness.

  Baseline, Endpoint (Month 12 or last post-baseline visit)

• Summary of Minnesota Impulsive Disorder Interview (MIDI) Assessment of Intense Impulsive Behavior at Baseline (BL) and Post-baseline (PBL)

  The MIDI is a validated assessment of impulsive behavior consisting of a semistructured clinical interview assessing pathological gambling, trichotillomania (compulsive hair-pulling), kleptomania (compulsive stealing), pyromania (compulsive fire-setting), intermittent explosive disorder, compulsive buying, and compulsive sexual behavior.

  Baseline, Post-baseline (up to Month 12)

• Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score at Endpoint

  The AIMS is an investigator-completed rating scale that has a total of 12 items rating involuntary movements of various areas of the participant's body. Items 1 through 10 are rated on a 5-point scale of severity from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe), and items 11 and 12 are yes/no questions concerning problems with teeth or dentures. The total AIMS score was calculated by summing items 1-10, with a possible range of 0-40; a negative change indicates improvement. The AIMS was to be performed at consistent times, when the subject was experiencing his/her worst "On" time (dyskinesia \[involuntary muscle movement\]).

  Baseline, Endpoint (Month 12 or last post-baseline visit)

• Number of Participants With Confirmed Cases of Melanoma

  A comprehensive assessment for the presence of melanoma was performed during the screening period and at early termination/end of study by a dermatologist experienced with the diagnosis of the condition. If a suspicious lesion was present, a biopsy was obtained for proper diagnosis.

  up to Month 12

• Number of Participants With Clinically Significant Neurological Examination Findings

  The neurologic examination was to be done during "On" time. The neurological examination assessed: cranial nerves - assessment of cranial nerves II - XII, excluding fundoscopic examination; motor system - assessment of tone, strength, and abnormal movements; sensory system - including light touch, pinprick, joint position, and vibratory sense; reflexes - assessment of deep tendon reflexes and plantar responses (Babinski sign); coordination - assessment of upper and lower extremities; gait - assessment of base and tandem gait; station - assessment of posture and stability.

  up to 12 months

• Columbia-Suicide Severity Rating Scale (C-SSRS) Findings

  The Columbia-Suicide Severity Rating Scale (C-SSRS) is a systematically administered instrument developed to track suicidal adverse events across a treatment study. The instrument is designed to assess suicidal behavior and ideation, track and assess all suicidal events, as well as the lethality of attempts. Suicidal ideation categories include the following: wish to be dead; nonspecific active suicidal thoughts; active suicidal ideation without intent to act; active suicidal ideation with some intent to act but no plan; active suicidal ideation with plan and intent. Suicidal behavior categories include the following: actual attempt; interrupted attempt; aborted attempt; preparatory acts or behavior; suicidal behavior; completed suicide.

  up to 12 months

• Number of Participants Taking at Least 1 Concomitant Medication During the Study

  Concomitant medications include medications started on or after the first open-label LCIG infusion as well as medications started prior to the first open-label infusion but continued during the study.

  12 months

Secondary Outcomes (21)

• Change From Baseline in Average Daily "Off" Time at Endpoint

  Baseline, Endpoint (Month 12 or last post-baseline visit)

• Change From Baseline in Average Daily Normalized "On" Time With Troublesome Dyskinesia at Endpoint

  Baseline, Endpoint (Month 12 or last post-baseline visit)

• Change From Baseline in Average Daily "On" Time Without Troublesome Dyskinesia at Month 12

  Baseline, Endpoint (Month 12 or last post-baseline visit)

• Clinical Global Impression - Status (CGI-S) Score at Baseline and Clinical Global Impression - Improvement (CGI-I) Score at Endpoint

  Baseline, Endpoint (Month 12 or last post-baseline visit)

• Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Endpoint

  Baseline, Endpoint (Month 12 or last post-baseline visit)

Study Arms (1)

Levodopa-Carbidopa Intestinal Gel (LCIG)

EXPERIMENTAL

All participants received LCIG, delivered through a percutaneous endoscopic gastrostomy with jejunal extension (PEG-J), administered for up to 12 months (52 weeks). Starting dose of LCIG was based on the participant's optimized oral levodopa-carbidopa dose that the subject was receiving just prior to randomization in Study S187.3.001 (NCT00357994) or Study S187.3.002 (NCT00660387), administered in the morning of the first day following Study Day 86 of either of these 2 previous studies. The LCIG infusion was expected to infuse over approximately16 hours each day with a rate of infusion within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances.

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

Interventions

Levodopa-carbidopa intestinal gel DRUG

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).

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:

• Idiopathic Parkinson's disease (PD) according to United Kingdon Parkinson's Disease Society (UKPDS) Brain Bank Criteria
• Levodopa-responsive with severe motor fluctuations

You may not qualify if:

• Patients with medically relevant abnormal findings (labs, electrocardiogram \[ECG\], physical examination, adverse events, psychiatric, neurological or behavioral disorders, etc.) at end of the double-blind phase (Week 12) of Study S187.3.001 (NCT00357994) or Study S187.3.002 (NCT00660387)

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Quintiles, Inc.: collaborator

Study Sites (22)

Site Reference ID/Investigator# 45869

Birmingham, Alabama, 35222, United States

Location

Site Reference ID/Investigator# 45834

Fountain Valley, California, 92708, United States

Location

Site Reference ID/Investigator# 45854

Los Angeles, California, 90033, United States

Location

Site Reference ID/Investigator# 45856

Oceanside, California, 92056, United States

Location

Site Reference ID/Investigator# 45859

Washington D.C., District of Columbia, 20007, United States

Location

Site Reference ID/Investigator# 45857

Bradenton, Florida, 34205, United States

Location

Site Reference ID/Investigator# 45863

Gainesville, Florida, 32610, United States

Location

Site Reference ID/Investigator# 45836

Port Charlotte, Florida, 33890, United States

Location

Site Reference ID/Investigator# 45874

Chicago, Illinois, 60611, United States

Location

Site Reference ID/Investigator# 45868

Lexington, Kentucky, 40536, United States

Location

Site Reference ID/Investigator# 45862

Baltimore, Maryland, 21201, United States

Location

Site Reference ID/Investigator# 45861

St Louis, Missouri, 63110, United States

Location

Site Reference ID/Investigator# 45873

New York, New York, 10032, United States

Location

Site Reference ID/Investigator# 45878

Cincinnati, Ohio, 45267, United States

Location

Site Reference ID/Investigator# 45850

Cleveland, Ohio, 44195-0001, United States

Location

Site Reference ID/Investigator# 45887

Burlington, Vermont, 05401, United States

Location

Site Reference ID/Investigator# 45828

Bochum, 44791, Germany

Location

Site Reference ID/Investigator# 45829

Bremerhaven, 27574, Germany

Location

Site Reference ID/Investigator# 45825

Hanover, 30625, Germany

Location

Site Reference ID/Investigator# 54402

Tübingen, 72076, Germany

Location

Site Reference ID/Investigator# 45884

Auckland, 1010, New Zealand

Location

Site Reference ID/Investigator# 45885

Hamilton, 3204, New Zealand

Location

Related Links

• Related Info

MeSH Terms

Conditions

Dyskinesias; Parkinson Disease

Interventions

Jejunostomy

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Janet Benesh

  AbbVie

  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: August 3, 2006
• First Posted: August 4, 2006
• Study Start: June 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: January 16, 2015
• Results First Posted: January 16, 2015

Record last verified: 2015-01

Locations

US (16); NZ (2); DE (4)