NCT03419806

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

Levodopa Pharmacokinetics in Patients With Parkinson's Disease and Symptom Fluctuation: A Phase I, Open-label, Randomized, Multicentre, Crossover Study Comparing Intravenous and Subcutaneous Infudopa With Intestinal Duodopa

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Vastra Gotaland Region · Other Government
• Sex: All
• Age: 30 Years
• Healthy volunteers: Not accepted

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.

Detailed description

IPO-001 is a prospective, randomized, 3-period cross-over, open-label multicentre trial comparing intravenous and subcutaneous Infudopa with intestinal Duodopa. The patients will be identified and recruited at neurology clinics at university hospital clinical sites in Sweden, and travel from their living location to a clinical phase I site with full Good Clinical Practice (GCP) standard at the Sahlgrenska University Hospital in Gothenburg for the three treatment visits. At the phase I study clinic, patients will receive Duodopa at optimal dosage for 16 hours at one of the treatment visits, i.v. Infudopa at a concentration estimated to yield corresponding serum levels of levodopa for the same duration at another treatment visit, and they will again receive the corresponding amount of levodopa but in the form of s.c. Infudopa at a third visit. The study will hence have a cross-over design with a minimum of three days on Duodopa between the different treatment visits, where the order of treatments will be non-blinded but randomized. Blood samples will be drawn according to a set schedule during the treatment visits, and subjects will be monitored for safety throughout the study, with focus on the local tolerability at the injection sites of i.v. and s.c. administration.

Conditions

• Parkinson Disease

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2018-02-16
• Primary completion: 2020-03-27
• Completion: 2020-04-20
• First posted: 2018-02-05
• Last updated: 2020-11-05

Locations

1 site across 1 country: Sweden