Pharmacokinetic Study in Healthy Volunteers (NOCOFPK2)

Pharmacokinetics of Levodopa After Repeated Doses of Carbidopa, ODM-104 and Levodopa: an Open, Randomised Study With Crossover Design in Healthy Males and Females

Phase I open, randomized cross-over pharmacokinetic study.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: levodopa, carbidopa, ODM-104; Drug: levodopa, carbidopa, entacapone

Detailed Description

The purpose of this study is to investigate the pharmacokinetics of levodopa, carbidopa, 3-OMD and ODM-104 after repeated doses of levodopa, carbidopa and ODM-104: an open, randomized, multicenter study with crossover design in healthy males and females.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland
    • Clinical Research Services Turku CRST

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent (IC) obtained
• Good general health ascertained by detailed medical history and physical examinations
• Finnish speaking males and females 18-65 years of age
• Normal weight defined as body mass index (BMI) 19-30 kg/m2 (BMI=weight/height m2)
• Weight at least 55 kg
• Regular intestinal transit (no recent history of recurrent constipation, diarrhea, or other intestinal problems, and no history of major gastrointestinal surgery)
• Sexually active study subjects, unless surgically sterile must adhere to a proper form of contraception (hormonal contraception or intrauterine device on female partner, and an additional barrier method used at least by one of the partners) from the first study treatment administration until 3 months after the end-of-study visit

Exclusion Criteria:

• Evidence of clinically significant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological or psychiatric disease or cancer (except local non-melanoma skin cancer) within the previous 2 years.
• Family history (parents, siblings) of clinically significant cardiac conduction disease.
• Any condition requiring regular concomitant treatment (including vitamins and herbal products) or likely to need any concomitant treatment during the study. As an exception, paracetamol for occasional pain is allowed. Hormonal contraception and hormone replacement therapy are allowed.
• Intake of any medication that could affect the outcome of the study.
• Any clinically significant abnormal laboratory value or physical finding (including ECG and vital signs) that in the opinion of the investigator could interfere with the interpretation of study results or cause a health risk for the subject if he/she takes part in the study.
• Known hypersensitivity to the active substances or the excipients of the drugs.
• Pregnant or lactating females.
• History of vasovagal collapses or vagal reactions with unexplained reason within the previous 2 years or a tendency for vasovagal reactions during blood sampling.
• HR < 40 bpm or > 90 bpm in the supine position after 10 min rest at the screening visit.
• At the screening visit:

systolic BP < 90 mmHg or > 150 mmHg in the supine position after 10 min rest diastolic BP < 50 mmHg or > 90 mmHg in the supine position after 10 min rest

• History of anaphylactic/anaphylactoid reactions.
• Strong tendency to motion sickness.
• Recent or current (suspected) drug abuse.
• Recent or current alcohol abuse; regular drinking of more than 21 units per week (males) or 16 units per week (females) (1 unit = 4 cl spirits or equivalent).
• Current use of nicotine containing products more than 5 cigarettes (or equivalent)/day and/or inability to refrain from the use of nicotine containing products during the study (from the screening visit to the end-of-study visit).

Use of caffeine containing beverages more than 600 mg of caffeine/day and/or inability to refrain from using caffeine containing beverages 24 h before the first levodopa administration on the PK day (day 7) until collection of the 24 h PK sample in the morning of day 8.

• Blood donation or loss of a significant amount of blood within 90 days before the first study treatment administration.
• Participation in an investigational drug study or administration of an investigational drug within 90 days before the first study treatment administration.
• Veins unsuitable for repeated venipuncture or cannulation.
• Predictable poor compliance or inability to communicate well with the study centre personnel.
• Inability to participate in all treatment periods.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levodopa standard carbidopa; Levodopa, carbidopa, ODM-104	Drug: levodopa, carbidopa, ODM-104; Other Names: Sinemet
Experimental: Levodopa modified carbidopa; Levodopa, carbidopa, ODM-104	Drug: levodopa, carbidopa, ODM-104; Other Names: Sinemet
Active Comparator: Stalevo; Levodopa, carbidopa, entacapone	Drug: levodopa, carbidopa, entacapone; Other Names: Stalevo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levodopa Peak Plasma Concentration (Cmax) and fluctuation of levodopa Cmax/Cmin, tau	Explore the Cmax of levodopa and fluctuation of levodopa Cmax/Cmin, tau	Blood samples collected frequently on day 7 for 24 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carbidopa Peak Plasma Concentration (Cmax)	Explore Cmax of carbidopa	Blood samples collected frequently on day 7 for 24 hours.
3-OMD Peak Plasma Concentration (Cmax)	Explore Cmax of 3-OMD	Blood samples collected frequently on day 7 for 24 hours.
Levodopa Cmax, tau	Explore Cmax, tau of levodopa	Blood samples collected frequently on day 7 for 24 hours.
Levodopa Cmin, tau	Explore Cmin, tau of levodopa	Blood samples collected frequently on day 7 for 24 hours.
Levodopa Area under the plasma concentration versus time curve (AUC)	Explore AUC of levodopa	Blood samples collected frequently on day 7 for 24 hours.
Carbidopa Area under the plasma concentration versus time curve (AUC)	Explore AUC of carbidopa	Blood samples collected frequently on day 7 for 24 hours.
3-OMD Area under the plasma concentration versus time curve (AUC)	Explore AUC of 3-OMD	Blood samples collected frequently on day 7 for 24 hours.
Levodopa Peak-trough fluctuation (PTF)	Explore PTF of levodopa	Blood samples collected frequently on day 7 for 24 hours.

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Mika Scheinin, MD, Clinical Research Services Turku CRST

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: September 17, 2015
• First Posted (Estimate): September 18, 2015

Study Record Updates

• Last Update Posted (Estimate): January 14, 2016
• Last Update Submitted That Met QC Criteria: January 13, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Entacapone
• Other Study ID Numbers: 3112003