A Study Comparing Efficacy of Levodopa-Carbidopa Intestinal Gel/Carbidopa-Levodopa Enteral Suspension and Optimized Medical Treatment on Dyskinesia in Subjects With Advanced Parkinson's Disease (DYSCOVER)

AbbVie

Status and phase: Completed; Phase 3

Conditions: Parkinson's Disease (PD)

Treatments: Device: Percutaneous endoscopic gastrostomy tube; Drug: Levodopa-Carbidopa Intestinal Gel (LCIG); Device: Jejunal extension tube; Device: CADD-Legacy ambulatory infusion pump; Drug: Optimized antiparkinsonian treatment

Study type: Interventional

Funder types: Industry

Identifiers

NCT02799381

2016-001403-23 (EudraCT Number)

M15-535

Details and patient eligibility

About

The primary objective of this study was to examine the effect of levodopa-carbidopa intestinal gel (LCIG) compared with optimized medical treatment (OMT) on dyskinesia in participants with advanced Parkinson's disease (PD).

Full description

This was a Phase 3b, open-label, randomized, multicenter, 12-week study. The study consisted of 3 sequential periods: Screening, Treatment, and Follow-Up. The OMT group had the same schedule of visits/procedures throughout the study as the LCIG treatment group, except for visits related to nasojejunal (NJ)/percutaneous endoscopic gastrostomy (PEG) procedures, titration of LCIG, and follow-up period.

Enrollment: 63 patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must have a diagnosis of idiopathic Parkinson's disease (PD) according to the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria
• Participants with advanced levodopa-responsive PD and persistent motor fluctuations who have not been controlled with optimized medical treatment (OMT: the maximum therapeutic effect obtained with pharmacological antiparkinsonian therapies when no further improvement is expected with regard to any additional manipulations of levodopa and/or other antiparkinsonian medication based on the Investigator's clinical judgment)
• Unified Dyskinesia Rating Scale (UDysRs) Total score ≥ 30 at Visit 3

Exclusion criteria

• Participant(s) treated with levodopa-carbidopa intestinal gel (LCIG) previously
• Participant's PD diagnosis is unclear or there is a suspicion that the subject has a parkinsonian syndrome such as secondary parkinsonism (e.g. caused by drugs, toxins, infectious agents, vascular disease, trauma, brain neoplasm), parkinson-plus syndrome (e.g. Multiple System Atrophy, Progressive supranuclear Palsy, Diffuse Lewy Body disease) or other neurodegenerative disease that might mimic the symptoms of PD
• Participant(s) has undergone neurosurgery for the treatment of Parkinson's disease.
• Participant(s) has contraindications to levodopa (e.g. narrow angle glaucoma, malignant melanoma)
• Participant(s) experiencing clinically significant sleep attacks or clinically significant impulsive behavior (e.g. pathological gambling, hypersexuality) at any point during the three months prior to the Screening evaluation as judged by the Principal Investigator

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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63 participants in 2 patient groups

Optimized Medical Treatment (OMT)

Active Comparator group

Description:

Participants randomized to OMT continued their current anti Parkinson's disease (anti-PD) medication regimen for the duration of the study. All anti-PD medications and medications to treat dyskinesia must have remained stable for the duration of the study unless adjustments were medically indicated. The Investigator provided the prescription for continued OMT.

Treatment:

Drug: Optimized antiparkinsonian treatment

Levodopa-Carbidopa Intestinal Gel (LCIG)

Experimental group

Description:

The total daily dose of infusion LCIG was composed of three components: (i) the morning dose, (ii) continuous maintenance infusion dose and (iii) extra doses. A temporary nasojejunal (NJ) tube may have been used initially with the infusion pump to determine a participant's response to this method of treatment and to optimize the dose of LCIG before treatment with a permanent percutaneous endoscopic gastrostomy - with jejunal extension (PEG-J) tube was started. Following optional NJ and/or PEG-J placement and, at the investigator's discretion, the participant may have begun initiation and titration of LCIG infusion on Day 1 once tube placement was confirmed. The dose of LCIG was adjusted to obtain the optimal clinical response. The rate of LCIG infusion is typically within the range of 1 to 10 mL/hour (20 to 200 mg of levodopa/hour) in most instances and runs over a period of 16 consecutive hours each day.

Treatment:

Device: Jejunal extension tube

Device: CADD-Legacy ambulatory infusion pump

Drug: Levodopa-Carbidopa Intestinal Gel (LCIG)

Device: Percutaneous endoscopic gastrostomy tube