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Healthy SubjectsPhase 1NCT02099071

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

A Phase 1 study testing ACT-389949 1 mg, ACT-389949 5 mg and ACT-389949 20 mg in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for
Healthy Subjects
What is being tested?
ACT-389949 1 mg, ACT-389949 5 mg and ACT-389949 20 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
65 participants
Where
1 siteNetherlands
Study dates
Nov 2011to May 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • QPS Netherlands BV

    Groningen, 9713 GZ

Other trials in Netherlands

About this study

Official title: Single-center, Double-blind, Randomized, Placebo-controlled, Single-ascending Dose and Food Interaction Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-389949 in Healthy Male Subjects

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.

Being tested
ACT-389949 1 mg, ACT-389949 5 mg, ACT-389949 20 mg, ACT-389949 50 mg, ACT-389949 100 mg
Keywords
ACT-389949

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ACT-389949 1 mgDrug

  • ACT-389949 5 mgDrug

  • ACT-389949 20 mgDrug

  • ACT-389949 50 mgDrug

  • ACT-389949 100 mgDrug

  • ACT-389949 200 mgDrug

  • ACT-389949 500 mgDrug

  • ACT-389949 1000 mgDrug

  • PlaceboDrug

Study groups in NCT02099071
Study groupRoleWhat they receive
Group 1ExperimentalSix 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.
Receives: Drug: ACT-389949 1 mg; Drug: Placebo
Group 2ExperimentalSix 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.
Receives: Drug: ACT-389949 5 mg; Drug: Placebo
Group 3ExperimentalSix 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.
Receives: Drug: ACT-389949 20 mg; Drug: Placebo
Group 4ExperimentalSubjects 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.
Receives: Drug: ACT-389949 50 mg; Drug: Placebo
Group 5ExperimentalSix 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.
Receives: Drug: ACT-389949 100 mg; Drug: Placebo
Group 6ExperimentalSix 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.
Receives: Drug: ACT-389949 200 mg; Drug: Placebo
Group 7ExperimentalSix 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.
Receives: Drug: ACT-389949 500 mg; Drug: Placebo
Group 8ExperimentalSix 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.
Receives: Drug: ACT-389949 1000 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 60 hours

  2. 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)

    Measured: 60 hours

  3. 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)

    Measured: 60 hours

  4. 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)

    Measured: 60 hours

  5. 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)

    Measured: 60 hours

  6. 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.

    Measured: 60 hours

  7. 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.

    Measured: 60 hours

  8. 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).

    Measured: 60 hours

  9. 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).

    Measured: 60 hours

  10. 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.

    Measured: 60 hours

Secondary outcomes (5)
  1. Maximum plasma concentration (Cmax) of ACT-389949

    Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours after dosing. Cmax will be calculated on the basis of the blood sampling time points.

    Measured: 60 hours

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

    Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours after dosing. AUC(0-t) will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification.

    Measured: 60 hours

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

    Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours after dosing. AUC(0-infinity) will be calculated by combining AUC(0-t) and AUC(extra). AUC(extra) represents an extrapolated value obtained by Ct/λz, where Ct is the last plasma concentration measured above the limit of quantification and λz represents the terminal elimination rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.

    Measured: 60 hours

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

    Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours after dosing. tmax will be calculated on the basis of the blood sampling time points.

    Measured: 60 hours

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

    Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-389949, and at 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, and 60 hours after dosing. t1/2 will be calculated on the basis of the blood sampling time points.

    Measured: 60 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2014 (estimated)
  2. Study startNov 2011
  3. Primary completionMay 2012
  4. Study completionMay 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02099071
Sponsor's protocol ID
AC-073-101
Status last verified
Jul 2018
First submitted
26 Mar 2014
Last updated
10 Jul 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ACT-389949 1 mg, ACT-389949 5 mg and ACT-389949 20 mg in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline up to 60 hours in supine systolic blood pressure (time frame: 60 hours). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2018.

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