Pharmacokinetic Study in Healthy Males (NOCOF)

Pharmacokinetics of Levodopa, Carbidopa, 3-OMD and ODM-104 After Repeated Doses of Different Formulations: an Open, Randomised, Multicentre Study With Crossover Design in Healthy Males

The purpose of this study is to investigate the pharmacokinetics of levodopa, carbidopa, 3-OMD and ODM-104 after repeated doses of 3 levodopa formulations given in combination with carbidopa and ODM-104.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20520
    • CRST

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Written informed consent (IC) obtained.
• Good general health ascertained by detailed medical history and physical examinations.
• Finnish speaking males 18-65 years of age (inclusive).
• Normal weight defined as a body mass index (BMI) > 19 and < 32 kg/m2 (BMI = weight/height2).
• Weight at least 60 kg.
• Regular intestinal transit (no recent history of recurrent constipation, diarrhoea, or other intestinal problems).
• Participants with female partners of child-bearing potential 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, malignancy, neurological or psychiatric disease within the previous 2 years.
• Inherited or family history (parents, siblings) of clinically significant cardiac conduction disease.
• Current/history of inflammatory bowel disease (IBDs): Colitis ulcerosa and Crohn's disease, celiac disease. Acute duodenal or gastric ulcer or gastritis, esophagitis, colon polyps or anal fissure.
• 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.
• 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 may interfere with the interpretation of study results or constitute a health risk for the subject if he takes part in the study.
• Known hypersensitivity to the active substances or the excipients of the drugs.
• History of vasovagal collapses or vagal reactions with unexplained reason within 2 years or a tendency for vasovagal reactions during blood sampling.
• History of sleep apnea.
• Heart rate (HR) < 40 bpm or > 90 bpm after 10 minutes in supine position at the screening visit and predose.
• At the screening visit:

systolic blood pressure (BP) < 90 mmHg or > 150 mmHg after 10 minutes in supine position diastolic BP < 50 mmHg or > 90 mmHg after 10 minutes in supine position

• Abnormal 24-hour Holter findings of clinical relevance according to cardiologist´s assessment at the screening visit.
• History of anaphylactic/anaphylactoid reactions.
• History of seizures excluding febrile seizures during the first 6 years of life.
• 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 (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 the use of caffeine containing beverages during the treatment periods until 24 hours after study treatment administration.
• Blood donation or loss of significant amount of blood within 90 days prior to the first study treatment administration.
• Administration of another investigational drug within 90 days prior to the first study treatment administration.
• Unsuitable veins for repeated venipuncture or for cannulation.
• Predictable poor compliance or inability to communicate well with the study centre personnel.
• Inability to participate in all treatment periods.
• Participation in a clinical drug study during or within 3 months prior to the first study treatment administration.

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levodopa formulation A; Levodopa formulation A together with ODM-104 100 mg and carbidopa	Drug: levodopa, carbidopa, ODM-104; Other Names: Sinemet
Experimental: levodopa formulation B; levodopa formulation B together with ODM-104 100 mg and carbidopa	Drug: levodopa, carbidopa, ODM-104; Other Names: Sinemet
Experimental: levodopa formulation C; levodopa formulation C together with ODM-104 100 mg and carbidopa	Drug: levodopa, carbidopa, ODM-104; Other Names: Sinemet
Active Comparator: Sinemet IR 100/25 mg; Sinemet IR 100/25 mg together with ODM-104 100 mg	Drug: levodopa, carbidopa, ODM-104; Other Names: Sinemet
Active Comparator: Half Sinemet CR 100/25 mg; Half Sinemet CR 100/25 mg together with ODM-104 100 mg	Drug: levodopa, carbidopa, ODM-104; Other Names: Sinemet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (Cmax) of levodopa	Peak Plasma Concentration (Cmax)	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (Cmax) of carbidopa, 3-OMD and ODM-104	Peak Plasma Concentration (Cmax)	24 hours

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: December 2, 2014
• First Submitted That Met QC Criteria: December 5, 2014
• First Posted (Estimate): December 9, 2014

Study Record Updates

• Last Update Posted (Estimate): February 18, 2015
• Last Update Submitted That Met QC Criteria: February 17, 2015
• Last Verified: February 1, 2015

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; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa
• Other Study ID Numbers: 3112002