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

NCT02448914 | Completed Phase 1 Results

• 2 other identifiers: LSM-0032014-004891-46
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

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

  During 14 h infusion on 2 consecutive days

Secondary Outcomes (4)

• Intra-individual Coefficient of Variation (3-14h) for Levodopa

  During 3-14h infusion on 2 consecutive days

• Dose Adjusted AUC (0-14h) for Carbidopa

  During 14 h infusion on 2 consecutive days

• Number of Adverse Events

  Patients will be followed for the duration of the hospital stay, an expected average of 3 days

• Dose Adjusted AUC (0-14h) for 3-O-Methyldopa

  During 14 h infusion on 2 consecutive days

Other Outcomes (1)

• Treatment Response Scale (ON/OFF Effect) - Mean % of Time Patients Were in Functional ON State During 3-14 h

  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.

Study Arms (2)

TRIGEL first, then Duodopa

EXPERIMENTAL

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; Drug: Duodopa

Duodopa first, then TRIGEL

EXPERIMENTAL

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; Drug: Duodopa

Interventions

TRIGEL DRUG

All patients will receive TRIGEL. Treatment order is determined by randomization.

Also known as: Lecigon

Duodopa first, then TRIGEL; TRIGEL first, then Duodopa

Duodopa DRUG

All patients will receive Duodopa. Treatment order is determined by randomization.

Also known as: Duopa

Duodopa first, then TRIGEL; TRIGEL first, then Duodopa

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• LobSor Pharmaceuticals AB: lead
• TFS Trial Form Support: collaborator

Study Sites (1)

Clinical Trial Consultants AB

Uppsala, SE-75185, Sweden

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Roger Bolsöy, CEO
• Organization: LobSor Pharmaceutical AB

roger.bolsoy@lsmgroup.se

+46 (0) 72 222 44 08

Study Officials

• Dag Nyholm, Assoc. Prof.

  Department of Neuroscience, Neurology, Uppsala University Hospital, Sweden

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: May 20, 2015
• Study Start: May 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: May 23, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-04

Locations

SE (1)