Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ODM-104 in Healthy Volunteers (NOCIFIM)

Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Single and Repeated Escalating Doses of ODM-104: a Randomised, Double-blind, Placebo- and Entacapone-controlled Single Centre First-in-man Study in Healthy Volunteers.

The purpose of this study is to evaluate the safety and tolerability of escalating doses of ODM-104 when given to healthy male volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: ODM-104; Drug: Entacapone; Drug: levodopa/carbidopa

Detailed Description

The study is divided into two parts. Part one is a crossover study where healthy volunteers will receive two doses of ODM-104 and one dose of placebo. Part II of the study is a multiple ascending dose parallel group study where healthy volunteers will receive ODM-104 three times daily for seven days. Healthy volunteers taking part in Part II of the study will also receive levo/carbidopa and entacapone four times daily on day 1 and levo/carbidopa in addition to ODM-104 on day 9. The study will also look at the pharmacokinetic(how the body handles the drug) and pharmacodynamics (how the drug affects the body) of ODM-104.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Parexel International GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male subjects aged between 18 and 45 years
• BMI 18-30 kg/m2
• Weight 55-95kg
• Written informed consent
• Good General Health

Exclusion Criteria:

• Vulnerable subjects
• Veins unsuitable for repeated venipuncture
• Evidence of clinically significant cardiovascular, renal, hepatic, hematological, Gi, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disorder
• History of or positive test for drug abuse
• Any condition requiring regular concomitant medication
• Blood donation or significant loss of blood within 2 months prior to screening
• Abnormal 12 lead ECG finding of clinical relevance
• Heart rate (HR) <50bpm or >90bpm after 10 minutes in a supine position
• Systolic blood pressure <90mmHg or >140mmHg after 10 minutes in a supine position
• Diastolic blood pressure <50mmHg or >90mmHg after 10 minutes in a supine position
• Abnormal 24 hour Holter recording of clinical relevance at screening
• Any abnormal laboratory value, vital signs or physical examination causing a health risk to the volunteer

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ODM-104; Oral capsules dosage 10-800mg once daily for one day or three times daily for 7 days	Drug: ODM-104; ODM-104
PLACEBO_COMPARATOR: Placebo; Oral capsules given once daily for one day or three times daily for 7 days	Drug: Placebo; Placebo
ACTIVE_COMPARATOR: entacapone + levodopa/carbidopa; entacapone: oral tablet 200mg given four times daily for one day; levodopa/carbidopa: oral tablet 100/25mg given four times daily for one day	Drug: Entacapone; entacapone + levodopa/carbidopa; Drug: levodopa/carbidopa; entacapone + levodopa/carbidopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Erythrocyte Catechol-O-methyltransferase (COMT) inhibition.	Maximal COMT inhibition and area under the COMT inhibition curve (AUCC)	0, 0.16, 0.33, 0.5, 0.75,1.0,1.5, 2, 3, 4, 6, 10, 16, 24h post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration curve (AUC)	AUC under the plasma concentration curve	0, 0.16, 0.33, 0.5, 0.75, 1, 1.5, 2, 2, 4, 6, 10, 16, 24h post dose

Collaborators and Investigators

• Sponsor: Orion Corporation, Orion Pharma
• Investigators: Study Director: angela ruck, PhD, Orion Corporation, Orion Pharma

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: April 23, 2013
• First Submitted That Met QC Criteria: April 24, 2013
• First Posted (ESTIMATE): April 25, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2015
• Last Update Submitted That Met QC Criteria: March 31, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: First in man study; Volunteer study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa; Entacapone
• Other Study ID Numbers: 3112001