Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-389949

NCT ID: NCT02099071

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-05-31

Brief Summary

This is a prospective, single-center, double-blind, randomized, placebo-controlled, ascending single oral dose and food interaction Phase 1 study. It will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ascending single oral doses of ACT-389949 in healthy male subjects. It will also investigate the effect of food on the pharmacokinetics, safety, and tolerability of a single dose of ACT-389949.

Conditions

Healthy Subjects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Group 1

Six subjects will receive a single oral dose of ACT-389949 1 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Group Type: EXPERIMENTAL

ACT-389949 1 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group 2

Six subjects will receive a single oral dose of ACT-389949 5 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Group Type: EXPERIMENTAL

ACT-389949 5 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group 3

Six subjects will receive a single oral dose of ACT-389949 20 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Group Type: EXPERIMENTAL

ACT-389949 20 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group 4

Subjects will participate in two different treatment periods separated by a washout of 7-10 days between the study drug administrations.

In the first treatment period six subjects will receive a single oral dose of ACT-389949 50 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

In the second treatment period, subjects randomized to ACT-389949 will receive a single oral dose of ACT-389949 50 mg in fed condition, 30 minutes after the start of a high fat and high calorie breakfast.

Group Type: EXPERIMENTAL

ACT-389949 50 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group 5

Six subjects will receive a single oral dose of ACT-389949 100 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Group Type: EXPERIMENTAL

ACT-389949 100 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group 6

Six subjects will receive a single oral dose of ACT-389949 200 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Group Type: EXPERIMENTAL

ACT-389949 200 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group 7

Six subjects will receive a single oral dose of ACT-389949 500 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Group Type: EXPERIMENTAL

ACT-389949 500 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group 8

Six subjects will receive a single oral dose of ACT-389949 1000 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Group Type: EXPERIMENTAL

ACT-389949 1000 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Interventions

ACT-389949 1 mg

Intervention Type: DRUG

ACT-389949 5 mg

Intervention Type: DRUG

ACT-389949 20 mg

Intervention Type: DRUG

ACT-389949 50 mg

Intervention Type: DRUG

ACT-389949 100 mg

Intervention Type: DRUG

ACT-389949 200 mg

Intervention Type: DRUG

ACT-389949 500 mg

Intervention Type: DRUG

ACT-389949 1000 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent prior to any study-mandated procedure.
• Healthy Caucasian male subjects aged between 18 and 45 years (inclusive) at screening.
• Subjects must agree to use reliable methods of contraception.
• No clinically significant findings on physical examination at screening.
• Body mass index (BMI) between 18.0 and 30.0 kg/m^2 (inclusive) at screening.
• Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate (PR) 45-90 bpm (inclusive) measured at screening.
• 12-lead ECG without clinically relevant abnormalities, measured at screening.
• Body temperature (T°) 35.5-37.5°C at screening and prior to (first) dosing.
• Total and differential white blood cell (WBC) count strictly within the normal ranges at screening and on Day -1.
• C-reactive protein (CRP) levels below 5 mg/L.
• Hematology and clinical chemistry results (other than total and differential WBC count and CRP) not deviating from the normal range to a clinically relevant extent at screening.
• Coagulation and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
• Non smokers, defined as never smoked or achieved cessation for ≥ 6 months at screening.
• Negative results from urine drug screen at screening.
• Subjects allowing the conduct of genetic analyses on whole blood consisting of measuring the levels of messenger ribonucleic acid (mRNA) expression of mechanistic biomarkers of N-formyl-peptide receptor 2 (FPR2) and proteins involved in inflammation.
• Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria

• Known allergic reactions or hypersensitivity to any excipient of the drug formulation.
• History or clinical evidence of any disease, and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
• Previous history of recurrent fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions.
• Veins unsuitable for intravenous (i.v.) puncture on either arm.
• Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Excessive caffeine consumption.
• Treatment with any prescribed or over-the-counter (OTC) medications within 2 weeks prior to (first) study drug administration or five half-lives of the medication, whichever is longer.
• Any history of immunosuppressive treatment.
• Chronic diseases including those with recurring periods of flare-ups and remission.
• History of atopic allergy (including asthma, urticaria, eczematous dermatitis).
• Signs of infection (viral, systemic fungal, bacterial or protozoal) within 4 weeks prior to (first) study drug administration.
• History of acute or chronic obstructive lung disease (treated or not treated).
• History of subarachnoid hemorrhage or hemolytic uremic syndrome.
• Interval from the beginning of the P wave to the beginning of the QRS complex (PQ/PR interval) < 120 ms at screening.
• Loss of 250 mL or more of blood, or an equivalent amount of plasma, within 3 months prior to screening.
• Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
• Positive results from the human immunodeficiency virus serology at screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity at screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hans Cruz, PhD

Role: STUDY_DIRECTOR

Actelion

Locations

QPS Netherlands BV

Groningen, , Netherlands

Countries

Netherlands

Other Identifiers

AC-073-101

Identifier Type: -

Identifier Source: org_study_id