Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of ODM-108: in Healthy Male Volunteers

NCT02432664 | Terminated Phase 1 DMC

• 1 other identifier: 3118001
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate to what extent this new study drug is tolerated in humans. The study is divided into 3 parts (Part III is optional and may go ahead depending on the results of Parts I and II). The volunteers will only be enrolled to one part of the study. In parts I and II the volunteer will receive active study drug or placebo. In part I the volunteers will receive a single dose of one of the eight planned escalating dose levels. In part II volunteers will receive 4 planned dose levels based on the results obtained in Part 1 of the study, with the option to include an additional dosing group. In optional part III the volunteer will receive ODM-108 and an already registered drug so that interactions with other drugs can be studied. It will be investigated how quickly and to what extent the study drug is absorbed and eliminated from the body (this is called pharmacokinetics). In addition, in parts I and II the effect of the compound on the sensation of pain and on cognition (activities of thinking, understanding, learning, and remembering) will be investigated (this is called pharmacodynamics).

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events in Part I and Part II.

  Clinically relevant changes from baseline of safety assessment

  From screening up to 8 weeks

Secondary Outcomes (33)

• Part III (optional) Effect of ODM-108 on the activity of CYP3A4 (cytochrome P450 3A4) isoenzymes

  Day 1 up to Day 11

• Part I Peak plasma concentration Cmax of ODM-108

  Pre dose,15, 30, 45 mins, 1 h, 1 h 15, 1 h 30, 2 h, 2 h 30, 3 h, 4 h, 6 h, 8 h, 12h, 24 h, 48 h, 72 h, 96 h post dose at each dose level.

• Part I Metabolite screening in plasma and urine

  Pre-dose and 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h and 48 h post dose at each dose level. Urine samples pre-dose and for 24 hours post dose at each dose level.

• Part I Sedation scores on Visual Analogue Scales

  Pre-dose, 2 h 30 min and 10 h post dose at each dose level

• Part I Cognitive function - Digital Symbol Substitution Test

  Pre-dose, 2 h 30 min and 10 h post dose at each dose level

Study Arms (6)

ODM-108 Part I

EXPERIMENTAL

Oral capsules dosage 0.2 - 240 mg once daily for one day

Drug: ODM-108 Part I

Placebo Part I

PLACEBO COMPARATOR

Oral capsules given once daily for one day

Drug: Placebo Part I

ODM-108 Part II

EXPERIMENTAL

Oral capsules 4 dose levels to be decided after Part 1 of the study. 1 - 4 times a day for 7 days

Drug: ODM-108-Part II

Placebo Part II

PLACEBO COMPARATOR

Oral capsules 1 - 4 times per day for 7 days

Drug: Placebo Part II

ODM-108 Part III

EXPERIMENTAL

Oral capsules 1-4 times daily for 7 to 10 days

Drug: ODM-108 Part III

Midazolam

ACTIVE COMPARATOR

Single dose as a solution 3 days prior to the first dose of ODM-108 and on the last day of dosing with ODM-108

Drug: Midazolam

Interventions

ODM-108 Part I DRUG

Single oral escalating dose of ODM-108. Each volunteer will receive either one dose of ODM-108 or placebo

ODM-108 Part I

Placebo Part I DRUG

Single oral escalating dose of ODM-108. Each volunteer will receive either one dose of ODM-108 or placebo

Placebo Part I

ODM-108-Part II DRUG

Multiple escalating doses based on the results of Part 1. Either ODM-108 or placebo 1 - 4 times a day for 7 days

ODM-108 Part II

Placebo Part II DRUG

Multiple escalating doses based on the results of Part 1. Either ODM-108 or placebo 1 - 4 times a day for 7 days

Placebo Part II

ODM-108 Part III DRUG

Oral capsules 1 - 4 times daily for 7 to 10 days

ODM-108 Part III

Midazolam DRUG

Single dose as a solution 3 days prior to the first dose of ODM-108 and on the last day of dosing with ODM-108

Midazolam

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent.
• Good general health
• Males between 18 and 55 years (inclusive).
• Body mass index (BMI) between 18-30 kg/m2 inclusive
• Weight 55-95 kg (inclusive).
• Participants with female partners of child-bearing potential must adhere to a proper form of contraception.
• Subjects with light coloured skin.

You may not qualify if:

• A predictable poor compliance or inability to understand and comply with the protocol , instructions and protocol restrictions or communicate well with the investigator.
• Vulnerable subjects.
• Veins unsuitable for repeated venipuncture.
• Evidence of clinically relevant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator.
• Medical history of relevant psychiatric disorders or evidence of clinically relevant neuropsychiatric disease.
• Suicidal ideation in the 6 months before screening or current risk of suicide based on the investigators judgement.
• History of hypersensitivity to drugs or excipients.
• Any condition requiring regular concomitant medication.
• Intake of any medication that could affect the outcome of the study.
• History of Alcoholism.
• Inability to refrain from using nicotine-containing products for 48 h before and during the stay in the study centre.
• History of drug abuse or positive drug screen.
• Blood donation or loss of a clinically relevant amount of blood within 2 months before the screening visit.
• Abnormal 12-lead ECG
• Heart rate \< 40 bpm or \> 100 bpm at screening.

Sponsors & Collaborators

• Orion Corporation, Orion Pharma: lead
• PRA Health Sciences: collaborator

Study Sites (1)

PRA Health Sciences

Zuidlaren, 9471GP, Netherlands

Location

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sjoerd van Marle, M.D

  PRA Health Sciences

  PRINCIPAL INVESTIGATOR

• Sara Haworth

  Orion Corporation, Orion Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2015
• First Posted: May 4, 2015
• Study Start: April 14, 2015
• Primary Completion: April 22, 2016
• Study Completion: April 22, 2016
• Last Updated: July 2, 2017

Record last verified: 2017-06

Locations

NL (1)