Pharmacokinetic of Levodopa Study in Healthy Males

Pharmacokinetics of Levodopa After Repeated Doses of Different Pellet Formulations; An Open, Randomized Study With Crossover Design in Healthy Male Subjects

The purpose of the study is to investigate PK of levodopa in plasma after repeated doses of 3 levodopa formulations given in combination with carbidopa and ODM-104 and compared to the PK of standard IR and CR levodopa formulations in the same combination.

Study Overview

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

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

Contacts and Locations

Study Locations

• Finland
  • Espoo, Finland, 02200
    • Clinical Pharmacology Unit, Orion Pharma

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.
• Finnish speaking males between 18-65 years of age.
• Body mass index (BMI) between 19-32 kg/m2 (BMI = weight/height2).
• Weight at least 60 kg.
• Regular intestinal transit (no recent history of recurrent constipation, diarrhoea, or other intestinal problems, 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) and must not donate sperm from the first study treatment administration until 3 months after the last study treatment administration.

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.
• 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.
• Any clinically significant abnormal laboratory value or ECG (such as prolonged QTcF > 450 ms or QRS > 120 ms) 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 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 the previous 2 years or a tendency for vasovagal reactions during blood sampling.
• HR < 40 beats per minute (bpm) or > 90 bpm in the supine position after 5 min rest at the screening visit.
• At the screening visit:systolic BP < 90 mmHg or > 150 mmHg in the supine position after 5 min rest and diastolic BP < 50 mmHg or > 90 mmHg in the supine position after 5 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 (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 10 h before and during the study periods.
• 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.
• Unsuitable veins 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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levodopa formulation D	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; Other Names: Sinemet
Experimental: Levodopa formulation E	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; Other Names: Sinemet
Experimental: Levodopa formulation F	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; Other Names: Sinemet
Active Comparator: Sinemet IR 100/25mg; Sinemet IR 100/25MG	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; Other Names: Sinemet
Active Comparator: Sinemet CR 100/25mg; Sinemet IR 100/25MG	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; Other Names: Sinemet
Experimental: ODM-104 100mg; ODM-104 100MG	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; Other Names: Sinemet
Active Comparator: Carbidopa 20mg; Carbidopa 20MG	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; Other Names: Sinemet
Active Comparator: Carbidopa 65mg; Carbidopa 65MG	Drug: Levodopa, carbidopa, ODM-104; Crossover design. Study treatments will be administered in randomized order 4 times a day.; 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

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2017
• Primary Completion (Actual): July 3, 2017
• Study Completion (Actual): August 3, 2017

Study Registration Dates

• First Submitted: April 12, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 4, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

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: 3112006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No