Safety, Tolerability, Pharmacokinetics and PharmacodynamicsPhase 1NCT01954615

Single-ascending Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-281959 / ACT-246475 in Healthy Male Subjects

A Phase 1 study testing 5 mg ACT-281959 prodrug formulation I (Group A), 20 mg ACT-281959 prodrug formulation I (Group B) and ACT-281959 prodrug formulation I (Groups C to G doses to be defined) in people with Safety, Tolerability, Pharmacokinetics and Pharmacodynamics, run by Idorsia Pharmaceuticals Ltd. at 1 site in France.

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

Who is it for?: Ages 18 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics
What is being tested?: 5 mg ACT-281959 prodrug formulation I (Group A), 20 mg ACT-281959 prodrug formulation I (Group B) and ACT-281959 prodrug formulation I (Groups C to G doses to be defined)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 49 participants
Where: 1 siteFrance
Study dates: Oct 2011to Mar 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 in the local language prior to any study-mandated procedure.
Healthy male subjects aged between 18 and 45 years (inclusive) at screening.
No clinically significant findings on the physical examination at screening.
Body mass index of 18.0 to 28.0 kg/m^2 (inclusive) at screening.
Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive), measured on the dominant arm, after 5 minutes in the supine position at screening.
12-lead electrocardiogram without clinically relevant abnormalities, measured after 5 minutes in the supine position at screening.

Show all 11Show fewer

Hematology, coagulation, clinical chemistry, and urinalysis test results not deviating to a clinically relevant extent from the normal range at screening.
Negative results from urine drug screen at screening.
Baseline value for maximal (at peak) platelet aggregation ≥ 50% light transmission aggregometry upon 20 μM adenosine diphosphate (ADP) activation at screening.
Baseline values of closure time tested with the platelet function analyser 100, for both cartridges Collagen/Epinephrine and Collagen/ADP below the upper limit of the normal range.
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(s).
History or clinical evidence of any disease and/or existence of any surgical or medical condition which would interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendectomy and herniotomy were allowed, while cholecystectomy was not allowed).
Previous history of fainting, collapse, orthostatic hypotension, or vasovagal reactions.
Family or personal history of bleeding (e.g., stroke, major trauma, or surgical intervention), or bleeding disorders (e.g., thrombocytopenia, clotting disturbances, intracranial vascular diseases, peptic ulcers), or reasonable suspicion of vascular malformations.
Platelet count ˂ 120x10^9/L at screening.
Veins unsuitable for intravenous puncture on either arm (e.g., veins that were difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture).

Show all 16Show fewer

Treatment with another investigational drug within 3 months prior to screening or participation 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, defined as ≥ 800 mg per day at screening.
Smoking within 3 months prior to screening and inability to refrain from smoking during the course of the study.
Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St. John's Wort) especially acetyl salicylic acid, non-steroidal anti-inflammatory, or any anticoagulant medication (e.g., heparin, warfarin), within 2 weeks prior to (the first) administration of study drug.
Loss of 250 mL or more of blood 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, would 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.

France1 site

Biotrial
Rennes, 35000

Other trials in France

About this study

Official title: A Single-center, Double-blind, Randomized, Placebo-controlled, Single-ascending Oral Dose and Food Interaction Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-281959 / ACT-246475 in Healthy Male Subjects

Study Part I is a single-ascending dose study. Healthy male subjects to be included in the study and randomized in 6 dose groups, Groups A-F (8 subjects per group). Of the 8 subjects per group, 6 subjects receive the investigational drug and 2 subjects receive matching placebo. Study Part II is a 3-period, crossover, single dose study. Nine healthy male subjects to be enrolled in one group (Group G). Each subject to receive 2 different formulations of the prodrug and one formulation of the active drug in a randomized sequence.

Read the detailed description

Study Part I is a prospective, single-center, double-blind, randomized, placebo-controlled, single-ascending dose, Phase 1 study. Approximately 48 healthy male subjects to be included in the study and randomized in 6 dose groups, Groups A-F (8 subjects per group). Of the 8 subjects per group, 6 subjects are to receive the investigational drug and 2 subjects to receive matching placebo. Study Part II is a prospective, single-center, open-label, randomized, 3-period, crossover, single dose, Phase 1 study. Nine healthy male subjects to be enrolled in one group, Group G. Each subject to receive 2 different formulations of the prodrug and one formulation of the active drug in a randomized sequence.

Conditions: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics
Being tested: 5 mg ACT-281959 prodrug formulation I (Group A), 20 mg ACT-281959 prodrug formulation I (Group B), ACT-281959 prodrug formulation I (Groups C to G doses to be defined), ACT-281959 prodrug formulation II (Group G dose to be defined), ACT-246475 (Group G dose to be defined)
Keywords: ACT-281959, ACT-246475

What participants receive

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

5 mg ACT-281959 prodrug formulation I (Group A)Drug
20 mg ACT-281959 prodrug formulation I (Group B)Drug
ACT-281959 prodrug formulation I (Groups C to G doses to be defined)Drug
ACT-281959 prodrug formulation II (Group G dose to be defined)Drug
ACT-246475 (Group G dose to be defined)Drug
Placebo (Groups A to F)Drug

Study groups in NCT01954615
Study group	Role	What they receive
Group A 5 mg ACT-281959 prodrug formulation I/placebo	Experimental	6 subjects to receive a single, oral dose of 5 mg ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Receives: Drug: 5 mg ACT-281959 prodrug formulation I (Group A); Drug: Placebo (Groups A to F)
Group B 20 mg ACT-281959 prodrug formulation I/placebo	Experimental	6 subjects to receive a single, oral dose of 20 mg ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Receives: Drug: 20 mg ACT-281959 prodrug formulation I (Group B); Drug: Placebo (Groups A to F)
Group C ACT-281959 prodrug formulation I/placebo	Experimental	Group C: 6 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Dose selection will be based on pharmacokinetic data derived from Groups A-B. Receives: Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined); Drug: Placebo (Groups A to F)
Group D ACT-281959 prodrug formulation I/placebo	Experimental	6 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Dose selection will be based on pharmacokinetic data derived from Groups A-C. Receives: Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined); Drug: Placebo (Groups A to F)
Group E ACT-281959 prodrug formulation I/placebo	Experimental	6 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Dose selection will be based on pharmacokinetic data derived from Groups A-D. Receives: Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined); Drug: Placebo (Groups A to F)
Group F ACT-281959 prodrug formulation I/placebo	Experimental	Food effect dose group: 6 subjects to receive a single, oral dose ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Following a 7-10 day washout period, subjects will receive the identical treatments administered in the first period. Medication to be administered in the fed state. Dose selection will be based on pharmacokinetic data derived from Groups A-E. Receives: Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined); Drug: Placebo (Groups A to F)
Group G ACT-281959 prodrug formulation I & II/ACT-246475	Experimental	9 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I (Treatment A), a single, oral dose of ACT-281959 prodrug formulation II (Treatment B), and a single, oral dose of ACT-246475 (Treatment C). Subjects will be equally randomized to one of 3 treatment sequences: ABC, BCA, and CAB. Treatments will be separated by 7-10 day washout periods. Medication to be administered in the fasted state. Data from Groups A-E will be used for pharmacometric modeling to guide the selection of doses to be used in Group G. Receives: Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined); Drug: ACT-281959 prodrug formulation II (Group G dose to be defined); Drug: ACT-246475 (Group G dose to be defined)

What is being measured

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

Change in supine systolic blood pressure from baseline up to the end of study
Blood pressure to be measured using an automatic oscillometric device. Measurements to be taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm will be used for all measurements. Measurements to be taken at 1, 2, 4, 8, 24, 48, and 72 hours post-dose.
Measured: 72 hours
Change in supine diastolic blood pressure from baseline up to the end of study
Blood pressure to be measured using an automatic oscillometric device. Measurements to be taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm will be used for all measurements. Measurements to be taken at 1, 2, 4, 8, 24, 48, and 72 hours post-dose.
Measured: 72 hours
Change in supine pulse rate from baseline up to the end of study
Pulse rate to be measured using an automatic oscillometric device. Measurements to be taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm will be used for all measurements. Measurements to be taken at 1, 2, 4, 8, 24, 48, and 72 hours post-dose.
Measured: 72 hours
Change in body weight from baseline up to the end of study
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: 72 hours
Change in PQ Interval from baseline up to the end of study
A standard 12-lead electrocardiogram (ECG) will be recorded in supine position after a 5-min rest period. The PQ interval is the time interval from the beginning of the P wave to the beginning of the QRS complex. Measurements to be taken at 1, 2, 4, 8, 24, 48 and 72 hours post-dose.
Measured: 72 hours
Change in QRS Interval from baseline up to the end of study
A standard 12-lead electrocardiogram (ECG) will be recorded in supine position after a 5-min rest period. The QRS interval is the time interval from the beginning of the Q wave to the end of the S wave.Measurements to be taken at 1, 2, 4, 8, 24, 48 and 72 hours post-dose.
Measured: 72 hours
Change in QT Interval from baseline up to the end of study
A standard 12-lead electrocardiogram (ECG) will be recorded in supine position after a 5-min rest period. The QT interval is the time interval from beginning of the Q wave until end of the T wave. Measurements to be taken at 1, 2, 4, 8, 24, 48 and 72 hours post-dose.
Measured: 72 hours

Secondary outcomes (8)

Maximum plasma concentration (Cmax) of ACT-246475
Blood samples for pharmacokinetic analysis taken immediately prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours, after dosing. Cmax calculated on the basis of the blood sampling time points.
Measured: 72 hours
Time to reach maximum plasma concentration (tmax) of ACT-246475
Blood samples for pharmacokinetic analysis taken immediately prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours, after dosing. tmax calculated on the basis of the blood sampling time points.
Measured: 72 hours
Area under the plasma concentration-time curve (AUC) from time 0 to time t of the last measured concentration (AUC0-t) of ACT-246475
Blood samples for pharmacokinetic analysis taken immediately prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours, after dosing. AUC0-t calculated on the basis of the blood sampling time points, according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification.
Measured: 72 hours
AUC from time zero to infinity (AUC0-∞) of ACT-246475
Blood samples for pharmacokinetic analysis taken immediately prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours, after dosing. AUC0-∞ was calculated by combining AUC0-t and AUCextra. AUCextra is 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 in the terminal elimination phase.
Measured: 72 hours
Terminal half-life (t1/2) of ACT-246475
Blood samples for pharmacokinetic analysis taken immediately prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 48, and 72 hours, after dosing. t1/2 calculated on the basis of the blood sampling time points.
Measured: 72 hours
Percentage inhibition of platelet aggregation following administration of ACT-281959 as prodrug formulation I
Adenosine diphosphate(ADP)-induced platelet aggregation will be measured using 2 different assays: Light transmission aggregometry (20 μM ADP) and VerifyNow P2Y12 (ADP receptor) assays Blood samples taken prior to dosing and at 1, 2, 3, 4, 8, 12 and 24 hours post-dosing.
Measured: 24 hours
Percentage inhibition of platelet aggregation following administration of ACT-281959 as prodrug formulation II
Adenosine diphosphate(ADP)-induced platelet aggregation will be measured using 2 different assays: Light transmission aggregometry (20 μM ADP) and VerifyNow P2Y12 (ADP receptor) assays Blood samples taken prior to dosing and at 1, 2, 3, 4, 8, 12 and 24 hours post-dosing.
Measured: 24 hours
Percentage inhibition of platelet aggregation following administration of ACT-246475
Adenosine diphosphate(ADP)-induced platelet aggregation will be measured using 2 different assays: Light transmission aggregometry (20 μM ADP) and VerifyNow P2Y12 (ADP receptor) assays Blood samples taken prior to dosing and at 1, 2, 3, 4, 8, 12 and 24 hours post-dosing.
Measured: 24 hours

Timeline

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

Oct 2011Mar 2012

First posted7 Oct 2013 (estimated)
Study startOct 2011
Primary completionMar 2012
Study completionMar 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Safety, Tolerability, Pharmacokinetics and PharmacodynamicsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01954615
Sponsor's protocol ID: AC-075-101
Status last verified: Jul 2018
First submitted: 27 Sep 2013
Last updated: 10 Jul 2018
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single-center, Double-blind, Randomized, Placebo-controlled, Single-ascending Oral Dose and Food Interaction Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-281959 / ACT-246475 in Healthy Male Subjects
ClinicalTrials.gov ID: NCT01954615
Acronym / sponsor ID: AC-075-101
Conditions: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics
Keywords: ACT-281959, ACT-246475
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 49 participants (actual)
Lead sponsor: Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
Study start: Oct 2011
Primary completion: Mar 2012 (actual)
Study completion: Mar 2012 (actual)
First posted: 7 Oct 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 7

Arm	Type	Receives
Group A 5 mg ACT-281959 prodrug formulation I/placebo	Experimental	Drug: 5 mg ACT-281959 prodrug formulation I (Group A), Drug: Placebo (Groups A to F)6 subjects to receive a single, oral dose of 5 mg ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state.
Group B 20 mg ACT-281959 prodrug formulation I/placebo	Experimental	Drug: 20 mg ACT-281959 prodrug formulation I (Group B), Drug: Placebo (Groups A to F)6 subjects to receive a single, oral dose of 20 mg ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state.
Group C ACT-281959 prodrug formulation I/placebo	Experimental	Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined), Drug: Placebo (Groups A to F)Group C: 6 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Dose selection will be based on pharmacokinetic data derived from Groups A-B.
Group D ACT-281959 prodrug formulation I/placebo	Experimental	Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined), Drug: Placebo (Groups A to F)6 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Dose selection will be based on pharmacokinetic data derived from Groups A-C.
Group E ACT-281959 prodrug formulation I/placebo	Experimental	Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined), Drug: Placebo (Groups A to F)6 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Dose selection will be based on pharmacokinetic data derived from Groups A-D.
Group F ACT-281959 prodrug formulation I/placebo	Experimental	Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined), Drug: Placebo (Groups A to F)Food effect dose group: 6 subjects to receive a single, oral dose ACT-281959 prodrug formulation I and 2 subjects to receive a single, oral dose of matching placebo. Medication to be administered in the fasted state. Following a 7-10 day washout period, subjects will receive the identical treatments administered in the first period. Medication to be administered in the fed state. Dose selection will be based on pharmacokinetic data derived from Groups A-E.
Group G ACT-281959 prodrug formulation I & II/ACT-246475	Experimental	Drug: ACT-281959 prodrug formulation I (Groups C to G doses to be defined), Drug: ACT-281959 prodrug formulation II (Group G dose to be defined), Drug: ACT-246475 (Group G dose to be defined)9 subjects to receive a single, oral dose of ACT-281959 prodrug formulation I (Treatment A), a single, oral dose of ACT-281959 prodrug formulation II (Treatment B), and a single, oral dose of ACT-246475 (Treatment C). Subjects will be equally randomized to one of 3 treatment sequences: ABC, BCA, and CAB. Treatments will be separated by 7-10 day washout periods. Medication to be administered in the fasted state. Data from Groups A-E will be used for pharmacometric modeling to guide the selection of doses to be used in Group G.

Who may qualify

Ages: 18 to 45 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

Signed informed consent in the local language prior to any study-mandated procedure.
Healthy male subjects aged between 18 and 45 years (inclusive) at screening.
No clinically significant findings on the physical examination at screening.
Body mass index of 18.0 to 28.0 kg/m^2 (inclusive) at screening.
Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive), measured on the dominant arm, after 5 minutes in the supine position at screening.

Key exclusion criteria (16 listed)

Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s).
History or clinical evidence of any disease and/or existence of any surgical or medical condition which would interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendectomy and herniotomy were allowed, while cholecystectomy was not allowed).
Previous history of fainting, collapse, orthostatic hypotension, or vasovagal reactions.
Family or personal history of bleeding (e.g., stroke, major trauma, or surgical intervention), or bleeding disorders (e.g., thrombocytopenia, clotting disturbances, intracranial vascular diseases, peptic ulcers), or reasonable suspicion of vascular malformations.
Platelet count ˂ 120x10^9/L at screening.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
5 mg ACT-281959 prodrug formulation I (Group A)	Drug	Group A 5 mg ACT-281959 prodrug formulation I/placebo
20 mg ACT-281959 prodrug formulation I (Group B)	Drug	Group B 20 mg ACT-281959 prodrug formulation I/placebo
ACT-281959 prodrug formulation I (Groups C to G doses to be defined)	Drug	Group C ACT-281959 prodrug formulation I/placebo, Group D ACT-281959 prodrug formulation I/placebo, Group E ACT-281959 prodrug formulation I/placebo, Group F ACT-281959 prodrug formulation I/placebo, Group G ACT-281959 prodrug formulation I & II/ACT-246475
ACT-281959 prodrug formulation II (Group G dose to be defined)	Drug	Group G ACT-281959 prodrug formulation I & II/ACT-246475
ACT-246475 (Group G dose to be defined)	Drug	Group G ACT-281959 prodrug formulation I & II/ACT-246475
Placebo (Groups A to F)	Drug	Group A 5 mg ACT-281959 prodrug formulation I/placebo, Group B 20 mg ACT-281959 prodrug formulation I/placebo, Group C ACT-281959 prodrug formulation I/placebo, Group D ACT-281959 prodrug formulation I/placebo, Group E ACT-281959 prodrug formulation I/placebo, Group F ACT-281959 prodrug formulation I/placebo

Primary outcome

Change in supine systolic blood pressure from baseline up to the end of study
Time frame: 72 hours
Blood pressure to be measured using an automatic oscillometric device. Measurements to be taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm will be used for all measurements. Measurements to be taken at 1, 2, 4, 8, 24, 48, and 72 hours post-dose.
Change in supine diastolic blood pressure from baseline up to the end of study
Time frame: 72 hours
Blood pressure to be measured using an automatic oscillometric device. Measurements to be taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm will be used for all measurements. Measurements to be taken at 1, 2, 4, 8, 24, 48, and 72 hours post-dose.
Change in supine pulse rate from baseline up to the end of study
Time frame: 72 hours
Pulse rate to be measured using an automatic oscillometric device. Measurements to be taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm will be used for all measurements. Measurements to be taken at 1, 2, 4, 8, 24, 48, and 72 hours post-dose.
Change in body weight from baseline up to the end of study
Time frame: 72 hours
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.
Change in PQ Interval from baseline up to the end of study
Time frame: 72 hours
A standard 12-lead electrocardiogram (ECG) will be recorded in supine position after a 5-min rest period. The PQ interval is the time interval from the beginning of the P wave to the beginning of the QRS complex. Measurements to be taken at 1, 2, 4, 8, 24, 48 and 72 hours post-dose.
Change in QRS Interval from baseline up to the end of study
Time frame: 72 hours
A standard 12-lead electrocardiogram (ECG) will be recorded in supine position after a 5-min rest period. The QRS interval is the time interval from the beginning of the Q wave to the end of the S wave.Measurements to be taken at 1, 2, 4, 8, 24, 48 and 72 hours post-dose.
Change in QT Interval from baseline up to the end of study
Time frame: 72 hours
A standard 12-lead electrocardiogram (ECG) will be recorded in supine position after a 5-min rest period. The QT interval is the time interval from beginning of the Q wave until end of the T wave. Measurements to be taken at 1, 2, 4, 8, 24, 48 and 72 hours post-dose.

8 secondary outcomes

Maximum plasma concentration (Cmax) of ACT-246475
Time frame: 72 hours
Time to reach maximum plasma concentration (tmax) of ACT-246475
Time frame: 72 hours
Area under the plasma concentration-time curve (AUC) from time 0 to time t of the last measured concentration (AUC0-t) of ACT-246475
Time frame: 72 hours
AUC from time zero to infinity (AUC0-∞) of ACT-246475
Time frame: 72 hours
Terminal half-life (t1/2) of ACT-246475
Time frame: 72 hours
Percentage inhibition of platelet aggregation following administration of ACT-281959 as prodrug formulation I
Time frame: 24 hours
Percentage inhibition of platelet aggregation following administration of ACT-281959 as prodrug formulation II
Time frame: 24 hours
Percentage inhibition of platelet aggregation following administration of ACT-246475
Time frame: 24 hours

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2018.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daniela Baldoni, PharmD PhD study director

Actelion

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 11 inclusion and 16 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 France. 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 in supine systolic blood pressure from baseline up to the end of study (time frame: 72 hours). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01954615.

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.