Dose-finding Pharmacokinetic Study in Healthy Males

NCT ID: NCT03055936

Last Updated: 2021-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-21
• Study Completion Date: 2017-06-09

Brief Summary

This is a phase I PK study in healthy males.

Detailed Description

This is a phase I, open, repeated dose, randomised PK study in healthy males. The study will consist of 4 parallel groups (Groups 1-4). All groups will have a crossover design with 4 treatment periods, each lasting for 7 days.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A1

levodopa 50 mg, carbidopa 12.5 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

B1

levodopa 50 mg, carbidopa 65 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

C1

levodopa 50 mg, carbidopa 65 mg, ODM-104 50 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

D1

levodopa 50 mg, carbidopa 65 mg, ODM-104 100 mg A4 ; B4 l; C4 ; D4 levodopa 100 mg, carbidopa 65 mg, ODM-104 100 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

A2

levodopa 100 mg, carbidopa 25 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

B2

levodopa 100 mg, carbidopa 65 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

C2

levodopa 100 mg, carbidopa 65 mg, ODM-104 50 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

D2

levodopa 100 mg, carbidopa 37,5 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

A3

levodopa 150 mg, carbidopa 65 mg, ODM-104 100 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

B3

levodopa 150 mg, carbidopa 65 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

C3

levodopa 150 mg, carbidopa 65 mg, ODM-104 50 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

D3

levodopa 150 mg, carbidopa 65 mg, ODM-104 100 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

A4

levodopa IR 100 mg (Sinemet), carbidopa 25 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

B4

levodopa 100 mg, carbidopa 65 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

C4

levodopa 100 mg, carbidopa 25 mg, ODM-104 100 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

D4

levodopa 100 mg, carbidopa 65 mg, ODM-104 100 mg

Group Type: EXPERIMENTAL

Levodopa

Intervention Type: DRUG

Levodopa 50 mg or 100 mg or 150 mg

Carbidopa

Intervention Type: DRUG

Carbidopa 12.5 mg or 25 mg or 65 mg

ODM-104

Intervention Type: DRUG

ODM-104 50 mg or 100 mg

Interventions

Levodopa

Levodopa 50 mg or 100 mg or 150 mg

Intervention Type: DRUG

Carbidopa

Carbidopa 12.5 mg or 25 mg or 65 mg

Intervention Type: DRUG

ODM-104

ODM-104 50 mg or 100 mg

Intervention Type: DRUG

Other Intervention Names

Sinemet

Eligibility Criteria

Inclusion Criteria

• Written informed consent (IC) obtained.
• Good general health ascertained by detailed medical history and physical examinations.
• Males between 18-65 years of age inclusive at screening.
• Body mass index (BMI) between 19-30 kg/m2 (BMI = weight/height2) inclusive at screening.
• Weight at least 55 kg inclusive at screening.
• Regular intestinal transit (no recent history of recurrent constipation, diarrhoea, or other intestinal problems, and no history of major gastrointestinal surgery).
• Subject with a partner of childbearing potential agrees to use adequate contraception from the first dose of study treatment until 90 days after the last dose of study treatment. Adequate methods of contraception include: Hormonal contraceptives, barrier methods (condom, diaphragm, cervical cap, etc.) in combination with a spermicide, intrauterine device and sexual abstinence.
• Subject agrees to not donate sperm from the first dose of study treatment until 90 days after the last dose of study treatment.

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 < 50 bpm or > 90 bpm in the supine position after 5 min rest at the screening visit.
• At the screening visit:

• systolic BP < 100 mmHg or > 140 mmHg in the supine position after 5 min rest
• diastolic BP < 50 mmHg or > 90 mmHg in the supine position after 5 min rest.
• Creatinine > 1.5 x upper limit of normal (ULN) and alanine aminotransferase or aspartate aminotransferase >1.25 x ULN at screening.
• 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 for 48 h before the first dose in each period until collection of the 24 h PK sample in the morning of day 8.
• 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 (> 500 ml) within 90 days before the first study treatment administration.
• Participation in another investigational drug study or administration of another investigational drug within 60 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis Strugala, DR.med.

Role: PRINCIPAL_INVESTIGATOR

Nuvisan GmbH

Locations

Nuvisan Pharma Services

Neu-Ulm, , Germany

Countries

Germany

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

3112005

Identifier Type: -

Identifier Source: org_study_id