Clinical trial NCT02448914: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Lead sponsor: LobSor Pharmaceuticals AB
Sponsor class: INDUSTRY
Collaborators: name: TFS Trial Form Support
First posted: 2015-05-20
Enrollment: 11
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Dose Adjusted Area Under the Curve (AUC) (0-14h) for Levodopa
timeFrame: During 14 h infusion on 2 consecutive days
Secondary outcomes:
measure: Intra-individual Coefficient of Variation (3-14h) for Levodopa
timeFrame: During 3-14h infusion on 2 consecutive days
measure: Dose Adjusted AUC (0-14h) for Carbidopa
timeFrame: During 14 h infusion on 2 consecutive days
measure: Number of Adverse Events
timeFrame: Patients will be followed for the duration of the hospital stay, an expected average of 3 days
measure: Dose Adjusted AUC (0-14h) for 3-O-Methyldopa
timeFrame: During 14 h infusion on 2 consecutive days
Other outcomes:
measure: Treatment Response Scale (ON/OFF Effect) - Mean % of Time Patients Were in Functional ON State During 3-14 h
timeFrame: 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.
Locations:
city: Uppsala
country: Sweden
facility: Clinical Trial Consultants AB
Study officials:
affiliation: Department of Neuroscience, Neurology, Uppsala University Hospital, Sweden
name: Dag Nyholm, Assoc. Prof.
role: PRINCIPAL_INVESTIGATOR
References: