Clinical trial NCT03055936: Dose-finding Pharmacokinetic Study in Healthy Males
Official title: A Dose-finding Study for Levodopa, Carbidopa and ODM-104 Test Formulations After Repeated Administration in Healthy Males
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Orion Corporation, Orion Pharma
Sponsor class: INDUSTRY
First posted: 2017-02-16
Enrollment: 56
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Levodopa Area Under the Concentration-time Curve From Time 0 to the 24 h PK Sample (AUC0-24) Time 0 to the 24 h PK Sample (AUC0-24)
timeFrame: During 24 hours
Secondary outcomes:
measure: Fluctuation of Levodopa Cmax/Cmin, Tau
timeFrame: 16 hours
measure: Levodopa Peak Plasma Concentration (Cmax)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan Pharma Services
Study officials:
affiliation: Nuvisan GmbH
name: Denis Strugala, DR.med.
role: PRINCIPAL_INVESTIGATOR
References: