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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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ClinicalTrials.gov Identifier: NCT02448914
Recruitment Status : Completed
First Posted : May 20, 2015
Results First Posted : May 23, 2016
Last Update Posted : May 23, 2016
Sponsor:
Collaborator:
TFS Trial Form Support
Information provided by (Responsible Party):
LobSor Pharmaceuticals AB

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug: TRIGEL Drug: Duodopa Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2015
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TRIGEL first, then Duodopa

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.

Drug: TRIGEL
All patients will receive TRIGEL. Treatment order is determined by randomization.
Other Name: Lecigon

Drug: Duodopa
All patients will receive Duodopa. Treatment order is determined by randomization.
Other Name: Duopa

Experimental: Duodopa first, then TRIGEL

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.

Drug: TRIGEL
All patients will receive TRIGEL. Treatment order is determined by randomization.
Other Name: Lecigon

Drug: Duodopa
All patients will receive Duodopa. Treatment order is determined by randomization.
Other Name: Duopa




Primary Outcome Measures :
  1. Dose Adjusted Area Under the Curve (AUC) (0-14h) for Levodopa [ Time Frame: During 14 h infusion on 2 consecutive days ]

Secondary Outcome Measures :
  1. Intra-individual Coefficient of Variation (3-14h) for Levodopa [ Time Frame: During 3-14h infusion on 2 consecutive days ]
    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.

  2. Dose Adjusted AUC (0-14h) for Carbidopa [ Time Frame: During 14 h infusion on 2 consecutive days ]
  3. Number of Adverse Events [ Time Frame: Patients will be followed for the duration of the hospital stay, an expected average of 3 days ]
  4. Dose Adjusted AUC (0-14h) for 3-O-Methyldopa [ Time Frame: During 14 h infusion on 2 consecutive days ]

Other Outcome Measures:
  1. Treatment Response Scale (ON/OFF Effect) - Mean % of Time Patients Were in Functional ON State During 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. ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02448914


Locations
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Sweden
Clinical Trial Consultants AB
Uppsala, Sweden, SE-75185
Sponsors and Collaborators
LobSor Pharmaceuticals AB
TFS Trial Form Support
Investigators
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Principal Investigator: Dag Nyholm, Assoc. Prof. Department of Neuroscience, Neurology, Uppsala University Hospital, Sweden

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Responsible Party: LobSor Pharmaceuticals AB
ClinicalTrials.gov Identifier: NCT02448914     History of Changes
Other Study ID Numbers: LSM-003
2014-004891-46 ( EudraCT Number )
First Posted: May 20, 2015    Key Record Dates
Results First Posted: May 23, 2016
Last Update Posted: May 23, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Carbidopa
Carbidopa, levodopa drug combination
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Levodopa
Entacapone
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors
Catechol O-Methyltransferase Inhibitors
Adjuvants, Immunologic
Immunologic Factors
Dopamine Agonists