Levodopa-Carbidopa Intestinal Gel Open-Label Study in Advanced Parkinson's Disease

NCT00335153 | Completed Phase 3 Results DMC

• 2 other identifiers: S187.3.0042006-005186-18
• Study Type: interventional
• Target: 354
• Locations: 16 countries
• Sites: 83

Brief Summary

The primary objective of this study will be to provide further evidence of the long-term safety and tolerability of levodopa-carbidopa intestinal gel (Duodopa®) over 12-months in participants with advanced Parkinson's disease (PD) and severe motor fluctuations.

Conditions

Advanced Parkinson's Disease

Keywords

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

Outcome Measures

Primary Outcomes (13)

• Number of Participants With Adverse Events (AEs), Serious Adverse Events (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.

  Screening through Day 378 + 30 days

• Number of Participants With Device Complications During the Nasojejunal (NJ) Test Period

  Complications of the infusion device were collected during the NJ Test period. Pump, intestinal tube, NJ tube, 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 post-procedural hemorrhage.

  NJ Test Period (from 2 to 14 days)

• Number of Participants With Device Complications During the Percutaneous Endoscopic Gastrostomy - With Jejunal Extension Tube (PEG-J) Surgery and Post-PEG Long Term Treatment Periods

  Complications of the infusion device were collected during the PEG-J Surgery and Post-PEG Long-Term Treatment periods. Pump, PEG-J, 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 post-procedural hemorrhage.

  PEG-J Surgery Period (from 2 to 14 days) through the Long Term Treatment Period (Day 28 to Day 378)

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

  Potentially clinically significant values for red blood cells (RBCs), hemoglobin, and hematocrit are specified for females (f) and males (m) separately in the category rows.

  Screening through Day 378

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

  Terms abbreviated in the table include aspartate aminotransferase (AST), upper limit of normal (ULN), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), female (f), and male (m).

  Screening through Day 378

• 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.

  up to 56 weeks

• 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.

  Screening through Day 378

• Number of Participants With Sleep Attacks at Baseline

  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. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.

  Baseline

• Number of Participants With Sleep Attacks During the Post-PEG Long-Term Treatment Period

  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. Those participants who reported 1 or more sleep attacks were asked to report the number of sleep attacks they experienced, whether they experienced sleepiness or drowsiness prior to the sleep attack, whether they experienced a 'bad' outcome or problem due to a sleep attack, and if so, how many 'bad' outcomes or problems they experienced.

  During the Post-PEG Long-Term Treatment Period (Day 28 through Day 378)

• Summary of Minnesota Impulsive Disorder Interview (MIDI) Assessment of Intense Impulsive Behavior at Baseline (BL) and During the Post-PEG Long-term Treatment (PPLT) Period

  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, during the Post-PEG Long-term Treatment Period (Day 28 through Day 378)

• 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 regarding issues 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 (last Post-PEG Long-Term Period visit up to Day 378)

• 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 or 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.

  Screening up to Day 378

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

  Concomitant medications include those 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.

  Screening up to Day 378

Secondary Outcomes (21)

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

  Baseline, Endpoint (last post-baseline visit up to Day 378)

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

  Baseline, Endpoint (last post-baseline visit up to Day 378)

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

  Baseline, Endpoint (last post-baseline visit up to Day 378)

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

  Baseline, Endpoint (last post-baseline visit up to Day 378)

• Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score at Month 12

  Baseline, Endpoint (last post-baseline visit up to Day 378)

Study Arms (1)

Levodopa-Carbidopa Intestinal Gel (LCIG)

EXPERIMENTAL

All participants were to receive LCIG, via the NJ tube during the nasojejunal (NJ) 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 Post-PEG-J Long-Term Treatment 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), 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 Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
• Levodopa-responsive with severe motor fluctuations
• Recognizable off and on state (motor fluctuations) confirmed by diary

You may not qualify if:

• Diagnosis is unclear or a suspicion of other parkinsonian syndromes exists such as secondary parkinsonism
• Undergone surgery for the treatment of PD
• Contraindications to levodopa (such as narrow angle glaucoma)

Sponsors & Collaborators

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

Study Sites (83)

Site Reference ID/Investigator# 50065

Birmingham, Alabama, 35222, United States

Location

Site Reference ID/Investigator# 50059

Fountain Valley, California, 92708, United States

Location

Site Reference ID/Investigator# 50048

Los Angeles, California, 90033, United States

Location

Site Reference ID/Investigator# 50076

Oceanside, California, 92056, United States

Location

Site Reference ID/Investigator# 50061

Englewood, Colorado, 80113, United States

Location

Site Reference ID/Investigator# 50079

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

Location

Site Reference ID/Investigator# 50077

Bradenton, Florida, 34205, United States

Location

Site Reference ID/Investigator# 50060

Fort Lauderdale, Florida, 33308, United States

Location

Site Reference ID/Investigator# 50049

Gainesville, Florida, 32610, United States

Location

Site Reference ID/Investigator# 50047

Jacksonville, Florida, 32209, United States

Location

Site Reference ID/Investigator# 50068

Port Charlotte, Florida, 33890, United States

Location

Site Reference ID/Investigator# 50046

Tampa, Florida, 33613, United States

Location

Site Reference ID/Investigator# 50062

Augusta, Georgia, 30912, United States

Location

Site Reference ID/Investigator# 50050

Chicago, Illinois, 60611, United States

Location

Site Reference ID/Investigator# 50078

Chicago, Illinois, 60612, United States

Location

Site Reference ID/Investigator# 50064

Lexington, Kentucky, 40536, United States

Location

Site Reference ID/Investigator# 50075

Shreveport, Louisiana, 71103, United States

Location

Site Reference ID/Investigator# 50080

Baltimore, Maryland, 21201, United States

Location

Site Reference ID/Investigator# 50074

Baltimore, Maryland, 21287, United States

Location

Site Reference ID/Investigator# 50073

St Louis, Missouri, 63110, United States

Location

Site Reference ID/Investigator# 50042

Omaha, Nebraska, 68198-2045, United States

Location

Site Reference ID/Investigator# 50072

Manhasset, New York, 11030, United States

Location

Site Reference ID/Investigator# 50067

New York, New York, 10029, United States

Location

Site Reference ID/Investigator# 50066

New York, New York, 10032, United States

Location

Site Reference ID/Investigator# 50069

Raleigh, North Carolina, 27607, United States

Location

Site Reference ID/Investigator# 50063

Winston-Salem, North Carolina, 27157, United States

Location

Site Reference ID/Investigator# 50043

Cincinnati, Ohio, 45267, United States

Location

Site Reference ID/Investigator# 50044

Cleveland, Ohio, 44195-0001, United States

Location

Site Reference ID/Investigator# 50058

Burlington, Vermont, 05401, United States

Location

Site Reference ID/Investigator# 50045

Kirkland, Washington, 98034, United States

Location

Site Reference ID/Investigator# 50070

Milwaukee, Wisconsin, 53226, United States

Location

Site Reference ID/Investigator# 46429

Adelaide, 5000, Australia

Location

Site Reference ID/Investigator# 46427

Heidelberg, 3084, Australia

Location

Site Reference ID/Investigator# 46425

Westmead, 2145, Australia

Location

Site Reference ID/Investigator# 54545

Edmonton, T6G 2B7, Canada

Location

Site Reference ID/Investigator# 46433

Montreal, H2L 4M1, Canada

Location

Site Reference ID/Investigator# 46434

Toronto, M5T 2S8, Canada

Location

Site Reference ID/Investigator# 46436

Brno, 65691, Czechia

Location

Site Reference ID/Investigator# 46438

Hradec Králové, 500 05, Czechia

Location

Site Reference ID/Investigator# 46435

Pardubice, 532 03, Czechia

Location

Site Reference ID/Investigator# 46437

Prague, 128 08, Czechia

Location

Site Reference ID/Investigator# 46439

Prague, 15006, Czechia

Location

Site Reference ID/Investigator# 48003

Lahti, 15850, Finland

Location

Site Reference ID/Investigator# 48028

Berlin, 12200, Germany

Location

Site Reference ID/Investigator# 48029

Berlin, 13088, Germany

Location

Site Reference ID/Investigator# 48036

Freiburg im Breisgau, 79106, Germany

Location

Site Reference ID/Investigator# 48034

Göttingen, 37075, Germany

Location

Site Reference ID/Investigator# 48022

Hanau, 63450, Germany

Location

Site Reference ID/Investigator# 48024

Hanover, 30625, Germany

Location

Site Reference ID/Investigator# 48035

Mainz, 55131, Germany

Location

Site Reference ID/Investigator# 49882

Tel Aviv, 64239, Israel

Location

Site Reference ID/Investigator# 50131

Arcugnano, 36057, Italy

Location

Site Reference ID/Investigator# 50132

Catania, 95125, Italy

Location

Site Reference ID/Investigator# 50128

Genoa, 16132, Italy

Location

Site Reference ID/Investigator# 50129

Lido di Camaiore, 55043, Italy

Location

Site Reference ID/Investigator# 50130

Naples, 80131, Italy

Location

Site Reference ID/Investigator# 50127

Rome, 00163, Italy

Location

Site Reference ID/Investigator# 50138

Nijmegen, 6532 SZ, Netherlands

Location

Site Reference ID/Investigator# 50126

Auckland, 1010, New Zealand

Location

Site Reference ID/Investigator# 50123

Christchurch, 8011, New Zealand

Location

Site Reference ID/Investigator# 50124

Hamilton, 3204, New Zealand

Location

Site Reference ID/Investigator# 50125

Wellington, 6002, New Zealand

Location

Site Reference ID/Investigator# 50140

Lodz, 93-113, Poland

Location

Site Reference ID/Investigator# 50139

Poznan, 61-485, Poland

Location

Site Reference ID/Investigator# 50136

Almada, 2805-267, Portugal

Location

Site Reference ID/Investigator# 50134

Coimbra, 3000-075, Portugal

Location

Site Reference ID/Investigator# 50135

Lisbon, 1649-035, Portugal

Location

Site Reference ID/Investigator# 50137

Porto, 4200-319, Portugal

Location

Site Reference ID/Investigator# 50143

Kazan', 420061, Russia

Location

Site Reference ID/Investigator# 50141

Moscow, 125367, Russia

Location

Site Reference ID/Investigator# 50145

Saint Petersburg, 193312, Russia

Location

Site Reference ID/Investigator# 50142

Saint Petersburg, 194044, Russia

Location

Site Reference ID/Investigator# 50147

Saint Petersburg, 197089, Russia

Location

Site Reference ID/Investigator# 50146

Saint Petersburg, 197706, Russia

Location

Site Reference ID/Investigator# 50154

Barcelona, 08003, Spain

Location

Site Reference ID/Investigator# 50152

Barcelona, 08025, Spain

Location

Site Reference ID/Investigator# 50202

Barcelona, 08035, Spain

Location

Site Reference ID/Investigator# 50155

Barcelona, 08036, Spain

Location

Site Reference ID/Investigator# 50153

Madrid, 28034, Spain

Location

Site Reference ID/Investigator# 50150

Bangkok, 10330, Thailand

Location

Site Reference ID/Investigator# 50151

Bangkok, 10700, Thailand

Location

Site Reference ID/Investigator# 50149

Liverpool, L9 7LJ, United Kingdom

Location

Site Reference ID/Investigator# 50148

London, WC1N 3BG, United Kingdom

Location

Related Publications (3)

• Chang FC, Kwan V, van der Poorten D, Mahant N, Wolfe N, Ha AD, Griffith JM, Tsui D, Kim SD, Fung VS. Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson's disease. J Clin Neurosci. 2016 Mar;25:41-5. doi: 10.1016/j.jocn.2015.05.059. Epub 2016 Jan 14.

  PMID: 26777085 DERIVED

• Lew MF, Slevin JT, Kruger R, Martinez Castrillo JC, Chatamra K, Dubow JS, Robieson WZ, Benesh JA, Fung VS. Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials. Parkinsonism Relat Disord. 2015 Jul;21(7):742-8. doi: 10.1016/j.parkreldis.2015.04.022. Epub 2015 Apr 28.

  PMID: 25962554 DERIVED

• Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, Lew MF, Odin P, Steiger M, Yakupov EZ, Chouinard S, Suchowersky O, Dubow J, Hall CM, Chatamra K, Robieson WZ, Benesh JA, Espay AJ. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord. 2015 Apr;30(4):500-9. doi: 10.1002/mds.26123. Epub 2014 Dec 24.

  PMID: 25545465 DERIVED

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: June 8, 2006
• First Posted: June 9, 2006
• Study Start: January 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: January 16, 2015
• Results First Posted: January 16, 2015

Record last verified: 2015-01

Locations

GB (2); RU (6); PT (4); CZ (5); PL (2); TH (2); IL (1); CA (3); DE (7); AU (3); IT (6); FI (1); ES (5); NL (1); NZ (4); US (31)