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A Study to Compare Plasma Levels of Levodopa, Carbidopa and Entacapone After TRIGEL or Duodopa Infusion in PD Patients

Primary Purpose

Parkinson's Disease

Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
TRIGEL
Duodopa
Sponsored by
LobSor Pharmaceuticals AB
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Disease

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Willing and able to provide informed consent and judged by the Investigator to have decision-making capacity
  2. Advanced levodopa-responsive idiopathic PD currently treated with Duodopa infusion since minimum 30 days
  3. 30 years of age or older
  4. BMI between 17.0 and 31.0 kg/m2, both inclusive
  5. Agreed to use adequate contraceptive measures:

Female patients who have been post-menopausal for more than one year or female patients of childbearing potential using a highly efficient method of contraception during the study (i.e. a method with less than 1% failure rate [e.g. sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomised partner]). Oral contraceptives in combination with other contraceptives are accepted.

Male patients being vasectomised or agreeing to use condoms during the study and having a partner who is using a highly efficient method of contraception as described above.

Exclusion Criteria:

  1. Hypersensitivity or allergy to the investigational medicinal product (IMP) or to chemically related products
  2. Contraindications for the use of levodopa or carbidopa or entacapone
  3. Needing a daily total dose of Duodopa during study participation exceeding 125 mL
  4. Increased fluctuation in clinical PD symptoms within 7 days prior to Screening
  5. Administration of an investigational drug within 3 months prior to Screening and/or current participation in another clinical study involving a pharmaceutical or a medical device class III
  6. Use of any forbidden medication as specified in Section 9.6 of the protocol
  7. Known hepatitis B, hepatitis C or HIV infection
  8. Donation of blood or plasma or major blood loss (≥500 mL) within 3 months prior to Screening
  9. Positive urine drug test (amphetamine, benzodiazepines, tetrahydrocannabinol, cocaine or opiates) at Screening
  10. Known alcohol abuse
  11. Unwilling to meet the requirements of the protocol
  12. Other medical or social reasons for exclusion at the discretion of the Investigator

Sites / Locations

  • Clinical Trial Consultants AB

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

TRIGEL first, then Duodopa

Duodopa first, then TRIGEL

Arm Description

First Intervention (Day 1): TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). Second Intervention (Day 2): Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). Both TRIGEL and Duodopa treatment consists of 3 individually adjusted and pre-defined doses: a morning dose, a continuous 14 h infusion, and extra bolus doses (if required). All TRIGEL doses correspond to 80% of the pre-study individually optimised doses of Duodopa. All Duodopa doses correspond to 100% of the pre-study individually optimized doses of Duodopa. Administration is done through duodenal or upper jejunal infusion via the patient's permanently inserted gastrojejunostomy tube by means of an ambulatory infusion pump.

First Intervention (Day 1): Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). Second Intervention (Day 2): TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). Both TRIGEL and Duodopa treatment consists of 3 individually adjusted and pre-defined doses: a morning dose, a continuous 14 h infusion, and extra bolus doses (if required). All TRIGEL doses correspond to 80% of the pre-study individually optimised doses of Duodopa. All Duodopa doses correspond to 100% of the pre-study individually optimized doses of Duodopa. Administration is done through duodenal or upper jejunal infusion via the patient's permanently inserted gastrojejunostomy tube by means of an ambulatory infusion pump.

Outcomes

Primary Outcome Measures

Dose Adjusted Area Under the Curve (AUC) (0-14h) for Levodopa

Secondary Outcome Measures

Intra-individual Coefficient of Variation (3-14h) for Levodopa
The individual patient's coefficient of variation (CV) of levodopa plasma concentration during administration of TRIGEL and Duodopa respectively between 3 and 14 h after start of study drug. CV=100*sqrt (exp (SDlog*SDlog)-1) were SDlog denotes the standard deviation computed on logged plasma concentrations.
Dose Adjusted AUC (0-14h) for Carbidopa
Number of Adverse Events
Dose Adjusted AUC (0-14h) for 3-O-Methyldopa

Full Information

First Posted
May 12, 2015
Last Updated
April 19, 2016
Sponsor
LobSor Pharmaceuticals AB
Collaborators
TFS Trial Form Support
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1. Study Identification

Unique Protocol Identification Number
NCT02448914
Brief Title
A Study to Compare Plasma Levels of Levodopa, Carbidopa and Entacapone After TRIGEL or Duodopa Infusion in PD Patients
Official Title
A Single Centre, Two-period, Open Label, Randomised, Cross-over Study to Assess Plasma Levodopa, Carbidopa and Entacapone Concentrations After Continuous Infusion of TRIGEL or Duodopa in Patients With Advanced Parkinson´s Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LobSor Pharmaceuticals AB
Collaborators
TFS Trial Form Support

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study evaluates the continuous addition of entacapone to infused levodopa and carbidopa on the pharmacokinetic (PK) profile in patients with advanced Parkinson's disease (PD). All patients will receive both study drugs, i.e. TRIGEL (levodopa, carbidopa, and entacapone) and Duodopa (levodopa and carbidopa), in randomized order.
Detailed Description
Intestinal infusion of Duodopa (levodopa and carbidopa) provides faster absorption, comparable levodopa bioavailability and significantly reduced intra-patient variability in levodopa concentrations relative to oral administration. TRIGEL also contains a third ingredient, entacapone. In tablet form, entacapone is shown to improve the bioavailability of levodopa and might extend the half-life of levodopa, avoiding deep troughs in levodopa plasma levels, and providing more continuous delivery of levodopa to the brain. The intention with the study is to confirm that TRIGEL administration increases the area under the curve (AUC) for levodopa by combining levodopa, carbidopa, and entacapone and thereby lower the daily levodopa dose needed. It is expected that TRIGEL administration will result in a similar intra-patient variability in plasma levodopa concentrations as Duodopa during continuous administration.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TRIGEL first, then Duodopa
Arm Type
Experimental
Arm Description
First Intervention (Day 1): TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). Second Intervention (Day 2): Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). Both TRIGEL and Duodopa treatment consists of 3 individually adjusted and pre-defined doses: a morning dose, a continuous 14 h infusion, and extra bolus doses (if required). All TRIGEL doses correspond to 80% of the pre-study individually optimised doses of Duodopa. All Duodopa doses correspond to 100% of the pre-study individually optimized doses of Duodopa. Administration is done through duodenal or upper jejunal infusion via the patient's permanently inserted gastrojejunostomy tube by means of an ambulatory infusion pump.
Arm Title
Duodopa first, then TRIGEL
Arm Type
Experimental
Arm Description
First Intervention (Day 1): Duodopa, intestinal gel (20 mg/mL levodopa and 5 mg/mL carbidopa monohydrate). Second Intervention (Day 2): TRIGEL, intestinal gel (20 mg/mL levodopa, 5 mg/mL carbidopa monohydrate, and 20 mg/mL entacapone). Both TRIGEL and Duodopa treatment consists of 3 individually adjusted and pre-defined doses: a morning dose, a continuous 14 h infusion, and extra bolus doses (if required). All TRIGEL doses correspond to 80% of the pre-study individually optimised doses of Duodopa. All Duodopa doses correspond to 100% of the pre-study individually optimized doses of Duodopa. Administration is done through duodenal or upper jejunal infusion via the patient's permanently inserted gastrojejunostomy tube by means of an ambulatory infusion pump.
Intervention Type
Drug
Intervention Name(s)
TRIGEL
Other Intervention Name(s)
Lecigon
Intervention Description
All patients will receive TRIGEL. Treatment order is determined by randomization.
Intervention Type
Drug
Intervention Name(s)
Duodopa
Other Intervention Name(s)
Duopa
Intervention Description
All patients will receive Duodopa. Treatment order is determined by randomization.
Primary Outcome Measure Information:
Title
Dose Adjusted Area Under the Curve (AUC) (0-14h) for Levodopa
Time Frame
During 14 h infusion on 2 consecutive days
Secondary Outcome Measure Information:
Title
Intra-individual Coefficient of Variation (3-14h) for Levodopa
Description
The individual patient's coefficient of variation (CV) of levodopa plasma concentration during administration of TRIGEL and Duodopa respectively between 3 and 14 h after start of study drug. CV=100*sqrt (exp (SDlog*SDlog)-1) were SDlog denotes the standard deviation computed on logged plasma concentrations.
Time Frame
During 3-14h infusion on 2 consecutive days
Title
Dose Adjusted AUC (0-14h) for Carbidopa
Time Frame
During 14 h infusion on 2 consecutive days
Title
Number of Adverse Events
Time Frame
Patients will be followed for the duration of the hospital stay, an expected average of 3 days
Title
Dose Adjusted AUC (0-14h) for 3-O-Methyldopa
Time Frame
During 14 h infusion on 2 consecutive days
Other Pre-specified Outcome Measures:
Title
Treatment Response Scale (ON/OFF Effect) - Mean % of Time Patients Were in Functional ON State During 3-14 h
Description
Dyskinesia and parkinsonism symptoms were evaluated throughout the study period as an assessment of the clinical response. To assess the ON/OFF effect the Treatment Response Scale (TRS) was used. The TRS ranges from -3 (severe "OFF") to +3 ("ON" with severe dyskinesia). Results from the TRS recordings are presented as the mean percentage of time patients were in functional ON state (TRS: -1 to +1) during the time interval 3-14 h.
Time Frame
TRS assessments were made every 30 minutes from start of study drug administration until 3 h, every hour between 3 and 14 h and every 30 minutes between 14 and 17 h.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Willing and able to provide informed consent and judged by the Investigator to have decision-making capacity Advanced levodopa-responsive idiopathic PD currently treated with Duodopa infusion since minimum 30 days 30 years of age or older BMI between 17.0 and 31.0 kg/m2, both inclusive Agreed to use adequate contraceptive measures: Female patients who have been post-menopausal for more than one year or female patients of childbearing potential using a highly efficient method of contraception during the study (i.e. a method with less than 1% failure rate [e.g. sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomised partner]). Oral contraceptives in combination with other contraceptives are accepted. Male patients being vasectomised or agreeing to use condoms during the study and having a partner who is using a highly efficient method of contraception as described above. Exclusion Criteria: Hypersensitivity or allergy to the investigational medicinal product (IMP) or to chemically related products Contraindications for the use of levodopa or carbidopa or entacapone Needing a daily total dose of Duodopa during study participation exceeding 125 mL Increased fluctuation in clinical PD symptoms within 7 days prior to Screening Administration of an investigational drug within 3 months prior to Screening and/or current participation in another clinical study involving a pharmaceutical or a medical device class III Use of any forbidden medication as specified in Section 9.6 of the protocol Known hepatitis B, hepatitis C or HIV infection Donation of blood or plasma or major blood loss (≥500 mL) within 3 months prior to Screening Positive urine drug test (amphetamine, benzodiazepines, tetrahydrocannabinol, cocaine or opiates) at Screening Known alcohol abuse Unwilling to meet the requirements of the protocol Other medical or social reasons for exclusion at the discretion of the Investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dag Nyholm, Assoc. Prof.
Organizational Affiliation
Department of Neuroscience, Neurology, Uppsala University Hospital, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Trial Consultants AB
City
Uppsala
ZIP/Postal Code
SE-75185
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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A Study to Compare Plasma Levels of Levodopa, Carbidopa and Entacapone After TRIGEL or Duodopa Infusion in PD Patients

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