Study Comparing Intravenous and Subcutaneous Infudopa With Intestinal Duodopa in Patients With Parkinson's Disease

Summary

In patients with Parkinson's disease, the characteristic motor symptoms, i.e., slowness of movement (bradykinesia), tremor and rigidity, are consequences of the progressive degeneration of neurons containing and releasing dopamine. The first-line treatment of Parkinson´s is oral administration of levodopa - a precursor to dopamine that (unlike dopamine) passes the blood brain barrier. After the first few years of treatment with levodopa, many patients do however develop a highly variable response to the drug characterised by rapid shifts between impaired locomotion and drug induced dyskinesias (referred to as the on-off syndrome). This is cased by the marked variation in serum levodopa levels following per oral administration, and it is known that intravenous administration of levodopa give a more stable level of levodopa with improved on-off symptoms.

Levodopa-carbidopa intestinal gel (LCIG) - under the name of Duodopa® - is delivered directly to the proximal jejunum via a tube connected to a portable infusion pump. Infusion of Duodopa in the jejunum bypasses gastric emptying, helping to avoid the fluctuation in plasma levodopa levels. However, while clearly confirming that an even administration of levodopa is of considerable benefit to Parkinson patients with on-off symptomatology, the LCIG approach is marred by the need for surgery (for the insertion of the intestinal tube) and various possible complications following this, as well as by side effects such as abdominal pain.

Researchers have now succeeded in producing a physiologically acceptable levodopa solution (called Infudopa) in a concentration allowing for a continuous intravenous (i.v.) or subcutaneous (s.c.) administration of therapeutic doses to humans. Early experience of this strategy confirms that both s.c. and i.v. administration of this solution results in even serum levodopa levels and markedly improved motor functioning. The aim of this study is to compare the pharmacokinetic profile of Infudopa administered i.v. and s.c. with that of Duodopa administered enterally in parkinsonian patients with on-off complications.

Conditions

• Parkinson Disease

Interventions

DRUG

Infudopa i.v.

Infudopa i.v. infusion will be given through an indwelling catheter placed in the arm. Infudopa i.v. will be delivered in 75% of the subject's individual pre-study dosing of Duodopa. From patient 6 and onwards: Infudopa IntraV, at 81% of the subject's individual pre-study daily Duodopa dose, will be delivered over a 16-h period and administered as a continuous fixed infusion rate preceded by a morning bolus dose. The i.v. morning bolus is 110% of the hourly continuous dose delivered at the rate of 60 ml/h (mixed volume rate Infudopa Active + Infudopa Buffer IntraV). The morning dose will not exceed 24 mL, corresponding to 240 mg levodopa. The maximum daily dose levodopa during i.v. administration is not allowed to exceed 3240mg (equal to 81% of the maximum allowed daily dosage for Duodopa that is 4000 mg).

DRUG

Infudopa s.c.

A suitable infusion needle will be placed laterally on the abdomen for the s.c. infusion of Infudopa. Infudopa s.c. will be delivered in the same dosage as the subject's individual pre-study dosing of Duodopa, as a morning rapid s.c. constant rate administration followed by continuous s.c. infusion up to 16 h. From patient 6 and onwards: Two infusion needles will be placed on the abdomen for the s.c. infusion of Infudopa SubC in 86% of the the subject's individual pre-study daily Duodopa dose. The intervention is given as a continuous fixed infusion rate for 16h preceded by a morning bolus dose. The s.c. morning bolus is 155% of the hourly continuous dose delivered at the rate of 80 ml/h (mixed volume rate Infudopa Active + Infudopa Buffer SubC). The morning dose will not exceed 30 mL. The maximum daily dose levodopa during s.c. administration is not allowed to exceed 3440mg (equal to 86% of the maximum allowed daily dosage for Duodopa that is 4000 mg).

DRUG

LCIG (Duodopa)

Duodopa will be administered directly to the proximal small intestine via a PEG-J tube connected to a portable infusion pump. Individually optimized dosing of Duodopa will be administered as a morning rapid constant rate administration followed by continuous infusion and, if needed, intermittent extra doses (subject-initiated based on symptom experience). The maximum daily dose levodopa during Duodopa administration should normally not exceed 3350 mg, and is not allowed to exceed 4000 mg. From patient 6 and onwards: The pre-study daily Duodopa dose will be delivered over a 16-h period and administered as a continuous fixed infusion rate preceded by a morning bolus dose. The morning bolus is 110% of the hourly continuous dose delivered at the rate of 40 ml/h. The morning dose will not exceed 15 mL, corresponding to 300 mg levodopa. The maximum daily dose levodopa is not allowed to exceed 4000mg.

Sponsors & Collaborators

• The Swedish Research Council

  collaborator OTHER_GOV

• Dizlin Medical Design AB

  collaborator UNKNOWN

• Göteborg University

  collaborator OTHER

• Vastra Gotaland Region

  lead OTHER_GOV

Principal Investigators

• Filip Bergquist, Ass Prof · Department of Pharmacolgy at Institute of Neuroscience and Physiology

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-02-16

Primary Completion

2020-03-27

Completion

2020-04-20

Countries

• Sweden

Study Locations