Dose-finding Pharmacokinetic Study in Healthy Males (COMDOS1)

Orion Pharma

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Levodopa; Drug: Carbidopa; Drug: ODM-104

Study type: Interventional

Funder types: Industry

Identifiers

NCT03055936

3112005

Details and patient eligibility

About

This is a phase I PK study in healthy males.

Full 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.

Enrollment: 56 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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56 participants in 16 patient groups

A1

Experimental group

Description:

levodopa 50 mg, carbidopa 12.5 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

B1

Experimental group

Description:

levodopa 50 mg, carbidopa 65 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

C1

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa

D1

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa

A2

Experimental group

Description:

levodopa 100 mg, carbidopa 25 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

B2

Experimental group

Description:

levodopa 100 mg, carbidopa 65 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

C2

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa

D2

Experimental group

Description:

levodopa 100 mg, carbidopa 37,5 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

A3

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa

B3

Experimental group

Description:

levodopa 150 mg, carbidopa 65 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

C3

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa

D3

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa

A4

Experimental group

Description:

levodopa IR 100 mg (Sinemet), carbidopa 25 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

B4

Experimental group

Description:

levodopa 100 mg, carbidopa 65 mg

Treatment:

Drug: Carbidopa

Drug: Levodopa

C4

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa

D4

Experimental group

Description:

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

Treatment:

Drug: Carbidopa

Drug: ODM-104

Drug: Levodopa