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

NCT02099071 | Completed Phase 1

• 1 other identifier: AC-073-101
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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

Keywords

ACT-389949

Outcome Measures

Primary Outcomes (10)

• Change from baseline up to 60 hours in supine systolic blood pressure

  Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)

  60 hours

• Change from baseline up to 60 hours in standing systolic blood pressure

  Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)

  60 hours

• Change from baseline up to 60 hours in supine diastolic blood pressure

  Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)

  60 hours

• Change from baseline up to 60 hours in standing diastolic blood pressure

  Blood pressure will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)

  60 hours

• Change from baseline up to 60 hours in pulse rate

  Pulse rate will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand)

  60 hours

• Change from baseline up to 60 hours in body temperature

  Body temperature will be measured in the sitting position using the same thermometer(s) for all the subjects and throughout the study.

  60 hours

• Change from baseline up to 60 hours in body weight

  Body weight will be measured using the same weighing scale for all subjects and throughout the study. The weighing scale should have a precision of at least 0.5 kg.

  60 hours

• Change from baseline up to 60 hours in QTcB interval

  A standard 12-lead electrocardiogram (ECG) is to be recorded at rest with the subject in the supine position for a 5-minute period. The QTcB interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Bazett's formula (QTcB = QT/RR\^0.5 where RR is 60/heart rate).

  60 hours

• Change from baseline up to 60 hours in QTcF interval

  A standard 12-lead ECG is to be recorded at rest with the subject in the supine position for a 5-minute period. The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcF = QT/RR\^0.33 where RR is 60/heart rate).

  60 hours

• Treatment-emergent ECG abnormalities from baseline up to 60 hours

  Treatment-emergent abnormalities will be determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting. Treatment-emergent ECG abnormalities are defined as ECG abnormalities occurring up to 60 h after study drug administration in each treatment period.

  60 hours

Secondary Outcomes (5)

• Maximum plasma concentration (Cmax) of ACT-389949

  60 hours

• Area under the plasma concentration-time curve (AUC(0-t)) of ACT-389949

  60 hours

• Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-389949

  60 hours

• Time to maximum plasma concentration (tmax) of ACT-389949

  60 hours

• Plasma half life (t1/2) of ACT-389949

  60 hours

Study Arms (8)

Group 1

EXPERIMENTAL

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.

Drug: ACT-389949 1 mg; Drug: Placebo

Group 2

EXPERIMENTAL

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.

Drug: ACT-389949 5 mg; Drug: Placebo

Group 3

EXPERIMENTAL

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.

Drug: ACT-389949 20 mg; Drug: Placebo

Group 4

EXPERIMENTAL

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.

Drug: ACT-389949 50 mg; Drug: Placebo

Group 5

EXPERIMENTAL

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.

Drug: ACT-389949 100 mg; Drug: Placebo

Group 6

EXPERIMENTAL

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.

Drug: ACT-389949 200 mg; Drug: Placebo

Group 7

EXPERIMENTAL

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.

Drug: ACT-389949 500 mg; Drug: Placebo

Group 8

EXPERIMENTAL

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.

Drug: ACT-389949 1000 mg; Drug: Placebo

Interventions

ACT-389949 1 mg DRUG

Group 1

ACT-389949 5 mg DRUG

Group 2

ACT-389949 20 mg DRUG

Group 3

ACT-389949 50 mg DRUG

Group 4

ACT-389949 100 mg DRUG

Group 5

ACT-389949 200 mg DRUG

Group 6

ACT-389949 500 mg DRUG

Group 7

ACT-389949 1000 mg DRUG

Group 8

Placebo DRUG

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6; Group 7; Group 8

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

QPS Netherlands BV

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Interventions

ACT-389949

Study Officials

• Hans Cruz, PhD

  Actelion

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 26, 2014
• First Posted: March 28, 2014
• Study Start: November 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

NL (1)