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

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02448914
• Other study ID #: LSM-003
• Secondary ID: 2014-004891-46
• Status: Completed
• Phase: Phase 1
• First received: May 12, 2015
• Last updated: August 27, 2015
• Start date: May 2015
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: LobSor Pharmaceuticals AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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. All patients will receive both study drugs, i.e. TRIGEL (levodopa, carbidopa, and entacapone) and Duodopa (levodopa and carbidopa), in randomized order.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• TRIGEL
All patients will receive TRIGEL. Treatment order is determined by randomization.
• Duodopa
All patients will receive Duodopa. Treatment order is determined by randomization.

Locations

Country	Name	City	State
Sweden	Clinical Trial Consultants AB	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
LobSor Pharmaceuticals AB	TFS Trial Form Support

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose adjusted AUC(0-14h) for levodopa		During 14 h infusion on 2 consecutive days	No
Secondary	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.	During 3-14h infusion on 2 consecutive days	No
Secondary	Dose adjusted AUC(0-14h) for carbidopa and 3-O-methyldopa		During 14 h infusion on 2 consecutive days	No
Secondary	Number of Adverse Events		Patients will be follwed for the duration of the hospital stay, an expected average of 3 days	Yes