HealthyPhase 1NCT02381496
A Study to Assess the Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Ascending Single Doses (Including Food Interaction) and Ascending Multiple Doses of ACT-453859, and Multiple Doses of Setipiprant (ACT-129968)
A Phase 1 study testing ACT-453859 1 mg, ACT-453859 3 mg and ACT-453859 10 mg in people with Healthy, run by Idorsia Pharmaceuticals Ltd..
Trial summary
This is a three-part study to assess the tolerability, safety, pharmacodynamics, and pharmacokinetics of ascending single doses (including food interaction) of ACT-453859 in healthy male subjects, of ascending multiple doses of ACT-453859 in healthy male and female subjects, and of multiple doses of setipiprant… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- ACT-453859 1 mg, ACT-453859 3 mg and ACT-453859 10 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- No sites listed yet
- Study dates
- Dec 2011to Apr 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed informed consent.
- Healthy male subjects (Part A), healthy male and female subjects for Parts B \& C.
- Hematology, coagulation (Part A and Part B only), clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent.
- No clinically significant findings on physical examination.
- Body mass index between 18.0 and 28.0 kg/m^2.
- Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 45-90 beats per minute.
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- 12-lead electrocardiogram without clinically relevant abnormalities.
- Negative results from urine drug screen and alcohol breath test.
- Able and willing to refrain from sunbathing, prolonged sun exposure, and artificial sunlight exposure such as solarium, and to limit skin and eye exposure to sunlight using appropriate precautions from the first dose until safety follow-up visit for Parts A and B.
- Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.
- For male subjects: consent that the female partner uses a medically acceptable method of contraception throughout the entire study period and for 90 days after the study is completed.
- For male subjects: agree not to donate sperm from the first drug administration until 90 days after completion of the study.
- For Part C, women of childbearing potential must have a negative serum pregnancy test and a negative urine pregnancy test pre-dose on Day 1 (of each treatment period for Part C). Women of childbearing potential must consistently and correctly use a reliable method of contraception, be sexually inactive or have a vasectomized partner.
- Willing to adhere to the prohibitions and restrictions specified in this protocol.
Who cannot join
- Previous history of fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions.
- Veins unsuitable for intravenous puncture on either arm.
- Treatment with any prescribed or over-the-counter medications within 2 weeks prior to first study drug administration.
- Treatment or substances known to inhibit cytochrome P (CYP) enzyme drug metabolism .
- Treatment or substances known to induce CYP enzyme drug metabolism.
- Treatment with another investigational drug within 3 months prior or participated in more than four investigational drug studies within 1 year prior to Screening. Subjects will not participate in more than one part of the study.
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- History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to Screening.
- 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 drugs.
- Excessive caffeine consumption.
- Smoking, tobacco use, or use of nicotine products within 3 months and inability to refrain from smoking during the course of the study.
- 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.
- Positive results from human immunodeficiency virus serology.
- 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.
- Pregnant or lactating women.
- Known allergic reactions or hypersensitivity to any excipients of the drug formulations.
- Difficulty in fasting or consuming standardized meals.
- Difficulty in swallowing whole tablets or capsules.
About this study
Official title: A Three-part Study to Assess the Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Ascending Single Doses (Including Food Interaction) of ACT-453859 in Healthy Male Subjects, of Ascending Multiple Doses of ACT-453859 in Healthy Male and Female Subjects, and of Multiple Doses of Setipiprant (ACT-129968) in Healthy Male and Female Subjects
This is a three-part study to assess the tolerability, safety, pharmacodynamics, and pharmacokinetics of ascending single doses (including food interaction) of ACT-453859 in healthy male subjects, of ascending multiple doses of ACT-453859 in healthy male and female subjects, and of multiple doses of setipiprant (ACT-129968) in healthy male and female subjects.
Read the detailed description
Part A of this study is a single-center, randomized, double-blind, placebo-controlled, single-ascending dose (SAD) design in healthy male subjects. In each cohort, eight subjects will be randomized as follows:
- Six male subjects will receive a single oral dose of ACT-453859, under fasted conditions.
- Two male subjects will receive matching placebo, under fasted conditions.
The doses of ACT-453859 were 1, 3, 10, 30, 100, 300, and 800 mg. Subjects in only one cohort (100 mg dose cohort) will come back for a second period of treatment under fed conditions.
Part B is a single-center, randomized, double-blind, placebo-controlled multiple-ascending dose (MAD) design in healthy male and female of subjects.
In each of 3 cohorts, eight subjects will be randomized to receive multiple doses of ACT-453859 or placebo once a day for 7 days as follows:
- Three male subjects will receive ACT-453859.
- Three female subjects will receive ACT-453859.
- One male subject will receive matching placebo.
- One female subject will receive matching placebo.
The doses of ACT-453859 will be 10, 100, and 800 mg per day.
Part C is a single-center and open-label design consisting of multiple oral doses of setipiprant given in a sequential design in healthy male and female subjects.
Eight subjects will be randomized to receive multiple doses of setipiprant for 7 days (only a single dose on Day 7), in Treatment Period I (TPI) and Treatment Period II (TPII), as follows:
- Four male subjects will receive setipiprant 500 mg twice a day (b.i.d.) in TPI and 1000 mg b.i.d. in TPII.
- Four female subjects will receive setipiprant 500 mg b.i.d. in TPI and 1000 mg b.i.d. in TPII.
- Conditions
- Healthy
- Being tested
- ACT-453859 1 mg, ACT-453859 3 mg, ACT-453859 10 mg, ACT-453859 30mg, ACT-453859 100 mg
- Keywords
- ACT-453859, ACT-463036, Setipiprant, Tolerability, safety, pharmacodynamics, pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACT-453859 1 mgDrug
Capsule
ACT-453859 3 mgDrug
Capsule
ACT-453859 10 mgDrug
Capsule
ACT-453859 30mgDrug
Capsule
ACT-453859 100 mgDrug
Capsule
ACT-453859 300 mgDrug
Capsule
ACT-453859 800 mgDrug
Capsule
PlaceboOther
Matching ACT-453859 placebo capsule
Setipiprant 500 mgDrug
Capsule
Setipiprant 1000 mgDrug
Capsule
| Study group | Role | What they receive |
|---|---|---|
| Part A: Cohort A1: ACT-453859 1 mg | Experimental | ACT-453859 1 mg or placebo, single dose, administered orally in the fasted state
* Six male subjects will receive ACT-453859
* Two male subjects will receive matching placebo Receives: Drug: ACT-453859 1 mg; Other: Placebo |
| Part A: Cohort A2: ACT-453859 3 mg | Experimental | ACT-453859 3 mg or placebo, single dose, administered orally in the fasted state
* Six male subjects will receive ACT-453859
* Two male subjects will receive matching placebo Receives: Drug: ACT-453859 3 mg; Other: Placebo |
| Part A: Cohort A3: ACT-453859 10 mg | Experimental | ACT-453859 10 mg or placebo, single dose, administered orally in the fasted state
* Six male subjects will receive ACT-453859
* Two male subjects will receive matching placebo Receives: Drug: ACT-453859 10 mg; Other: Placebo |
| Part A: Cohort A4: ACT-453859 30 mg | Experimental | ACT-453859 30 mg or placebo, single dose, administered orally in the fasted state
* Six male subjects will receive ACT-453859
* Two male subjects will receive matching placebo Receives: Drug: ACT-453859 30mg; Other: Placebo |
| Part A: Cohort A5: ACT-453859 100 mg | Experimental | ACT-453859 100 mg or placebo, single dose, administered orally in the fasted state
* Six male subjects will receive ACT-453859
* Two male subjects will receive matching placebo
After a washout period of 10-20 days subjects will return for a second study period to receive the same treatment received in the first session but under fed conditions Receives: Drug: ACT-453859 100 mg; Other: Placebo |
| Part A: Cohort A6: ACT-453859 300 mg | Experimental | ACT-453859 300 mg or placebo, single dose, administered orally in the fasted state
* Six male subjects will receive ACT-453859
* Two male subjects will receive matching placebo Receives: Drug: ACT-453859 300 mg; Other: Placebo |
| Part A: Cohort A7: ACT-453859 800 mg | Experimental | ACT-453859 800 mg or placebo, single dose, administered orally in the fasted state
* Six male subjects will receive ACT-453859
* Two male subjects will receive matching placebo Receives: Drug: ACT-453859 800 mg; Other: Placebo |
| Part B: Cohort B1: ACT-453859 10 mg | Experimental | ACT-453859 10 mg or placebo, once a day for 7 days, administered orally in the fasted state
* Three male subjects will receive ACT-453859
* Three female subjects will receive ACT-453859
* One male subject will receive matching placebo
* One female subject will receive matching placebo Receives: Drug: ACT-453859 10 mg; Other: Placebo |
| Part B: Cohort B2: ACT-453859 100 mg | Experimental | ACT-453859 100 mg or placebo, once a day for 7 days, administered orally in the fasted state
* Three male subjects will receive ACT-453859
* Three female subjects will receive ACT-453859
* One male subject will receive matching placebo
* One female subject will receive matching placebo Receives: Drug: ACT-453859 100 mg; Other: Placebo |
| Part B: Cohort B3: ACT-453859 800 mg | Experimental | ACT-453859 800 mg, once a day for 7 days, administered orally in the fasted state
* Three male subjects will receive ACT-453859
* Three female subjects will receive ACT-453859
* One male subject will receive matching placebo
* One female subject will receive matching placebo Receives: Drug: ACT-453859 800 mg; Other: Placebo |
| Part C: Treatment Periods I & II: Setipiprant | Experimental | Setipiprant 500 mg, twice daily for 7 days, administered orally in Treatment Period I (TPI) and setipiprant 1000 mg, twice daily for 7 days, administered orally in Treatment Period II (TPII)
* Four male subjects will receive setipiprant 500 mg twice a day in TPI and 1000 mg twice a day in TPII.
* Four female subjects will receive setipiprant 500 mg twice a day in TPI and 1000 mg twice a day in TPII.
There will be a washout period of 10 days between TPI and TPII Receives: Drug: Setipiprant 500 mg; Drug: Setipiprant 1000 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve (AUC(0-t)) for single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. AUC(0-t) will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification (LOQ).
Measured: 72 hours
AUC(0-t) for the active metabolite ACT-463036 after single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. AUC(0-t) will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the LOQ.
Measured: 72 hours
Area under the plasma concentration-time curve (AUC(0-infinity)) for single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. 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 LOQ 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: 72 hours
AUC(0-infinity) for the active metabolite ACT-463036 after single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. 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 LOQ 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: 72 hours
Time to reach maximum plasma concentration (tmax) for single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-453859 will be used to directly obtain tmax.
Measured: 72 hours
tmax for the active metabolite ACT-463036 after single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-463036 will be used to directly obtain tmax.
Measured: 72 hours
Terminal elimination rate constant (λZ) for single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. λZ will be determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
Measured: 72 hours
λZ for the active metabolite ACT-463036 after single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. λZ will be determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
Measured: 72 hours
Plasma half life (t1/2) for single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. t1/2 will be calculated as follows: t½ = ln 2/λZ.
Measured: 72 hours
t1/2 for the active metabolite ACT-463036 after single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. t1/2 will be calculated as follows: t½ = ln 2/λZ.
Measured: 72 hours
Maximum plasma concentration (Cmax) for single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-453859 will be used to directly obtain Cmax.
Measured: 72 hours
Cmax for the active metabolite ACT-463036 after single doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-463036 will be used to directly obtain Cmax.
Measured: 72 hours
Renal clearance (CLR) following single dose of ACT-453859 100 mg
Urine samples for pharmacokinetic assessments will be collected at various time points over the study period. CLR will be calculated by dividing the total amount of unchanged ACT-453859 excreted in urine during the collection interval by AUC(0-t).
Measured: 72 hours
Percentage of ACT-453859 excreted unchanged in the urine following single dose of ACT-453859 100 mg
Urine samples for pharmacokinetic assessments will be collected at various time points over the study period.The percentage of total dose excreted unchanged in urine will be calculated by the total amount excreted, divided by the dose administered, multiplied by 100.
Measured: 72 hours
Secondary outcomes (27)
Area under the plasma concentration-time curve (AUCτ) for multiple doses of ACT-453859 (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. AUCτ will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the LOQ during one dosing interval.
Measured: 11 days
AUCτ for the active metabolite ACT-463036 after multiple doses of ACT-453859 (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. AUCτ will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the LOQ during one dosing interval.
Measured: 11 days
Cmax for multiple doses of ACT-453859 (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-453859 will be used to directly obtain Cmax.
Measured: 11 days
Cmax for the active metabolite ACT-463036 after multiple doses of ACT-453859 (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-463036 will be used to directly obtain Cmax.
Measured: 11 days
tmax for multiple doses of ACT-453859 (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-453859 will be used to directly obtain tmax.
Measured: 11 days
tmax for the active metabolite ACT-463036 after multiple doses of ACT-453859 (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-463036 will be used to directly obtain tmax.
Measured: 11 days
λZ for multiple doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. λZ will be determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
Measured: 11 days
λZ for the active metabolite ACT-463036 after multiple doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. λZ will be determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
Measured: 11 days
t1/2 for multiple doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. t1/2 will be calculated as follows: t½ = ln 2/λZ.
Measured: 11 days
t1/2 for the active metabolite ACT-463036 after multiple doses of ACT-453859
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. t1/2 will be calculated as follows: t½ = ln 2/λZ.
Measured: 11 days
CLR following multiple doses of ACT-453859 100 mg per day
Urine samples for pharmacokinetic assessments will be collected at various time points over the study period. CLR will be calculated by dividing the total amount of unchanged ACT-453859 excreted in urine during the collection interval by AUC(0-t).
Measured: 8 days
Percentage of ACT-453859 excreted unchanged in the urine following multiple doses of ACT-453859 100 mg per day
Urine samples for pharmacokinetic assessments will be collected at various time points over the study period. The percentage of total dose excreted unchanged in urine will be calculated by the total amount excreted, divided by the dose administered, multiplied by 100.
Measured: 8 days
AUCτ for setipiprant after multiple doses of 500 and 1000 mg b.i.d. setipiprant (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. AUCτ will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the LOQ during one dosing interval.
Measured: 10 days
Cmax for setipiprant after multiple doses of 500 and 1000 mg b.i.d. setipiprant (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of setipiprant will be used to directly obtain Cmax.
Measured: 10 days
tmax for setipiprant after multiple doses of 500 and 1000 mg b.i.d. setipiprant (Day 1 & Day 7)
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of setipiprant will be used to directly obtain tmax.
Measured: 10 days
Chemoattractant receptor-homologous molecule expressed on T helper 2 cells (CRTH2) antagonist pharmacodynamic (PD) effect after single doses of ACT-453859
Blood samples for PD assessment will be collected at various time points over the study period. The CRTH2 receptor level on eosinophils and basophils will be measured with flow cytometry and the percentage of eosinophil and basophil CRTH receptors blocked determined.
Measured: 72 hours
CRTH2 antagonist PD effect after multiple doses of ACT-453859
Blood samples for PD assessment will be collected at various time points over the study period. The CRTH2 receptor level on eosinophils and basophils will be measured with flow cytometry and the percentage of eosinophil and basophil CRTH receptors blocked determined.
Measured: 10 days
CRTH2 antagonist PD effect after multiple doses of setipiprant
Blood samples for PD assessment will be collected at various time points over the study period. The CRTH2 receptor level on eosinophils and basophils will be measured with flow cytometry and the percentage of eosinophil and basophil CRTH receptors blocked determined.
Measured: 10 days
CRTH2 antagonist potency following administration of single and multiple doses of ACT-453859 and setipiprant
Study drug concentration that elicits 50% blockade (IC50) of eosinophil and basophil CRTH receptors.
Measured: up to 10 days
Change from baseline up to end of study in systolic blood pressure
Blood pressure and heart rate will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand). Measurements will be recorded from the subject in the supine and standing position after having rested for a 5-minute period, except for Part C in which only supine position measurements will be performed. Standing position measurements will be performed after one minute standing.
Measured: up to 11 days
Change from baseline up to end of study in diastolic blood pressure
Blood pressure and heart rate will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand). Measurements will be recorded from the subject in the supine and standing position after having rested for a 5-minute period, except for Part C in which only supine position measurements will be performed. Standing position measurements will be performed after one minute standing.
Measured: up to 11 days
Change from baseline up to end of study in heart rate
Blood pressure and heart rate will be measured using an automatic oscillometric device, always on the dominant arm (i.e., dominant arm right = writing with right hand). Measurements will be recorded from the subject in the supine and standing position after having rested for a 5-minute period, except for Part C in which only supine position measurements will be performed. Standing position measurements will be performed after one minute standing.
Measured: up to 11 days
Change from baseline up to end of study in QT interval (Time interval from beginning of the Q wave until end of the T wave)
Standard 12-lead electrocardiograms will be recorded at rest with the subject in the supine position for at least a 5-minute period at various time points throughout the study.
Measured: up to 11 days
Change from baseline up to end of study in QTcB interval (QT interval corrected for heart rate according to Bazett's correction)
Standard 12-lead electrocardiograms will be recorded at rest with the subject in the supine position for at least a 5-minute period at various time points throughout the study. The QTcB interval is the QT interval corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5 where RR is 60/heart rate).
Measured: up to 11 days
Change from baseline up to end of study in QTcF interval (QT interval corrected for heart rate according to Fridericia's correction)
Standard 12-lead electrocardiograms will be recorded at rest with the subject in the supine position for at least a 5-minute period at various time points throughout the study. The QTcF interval is the QT interval corrected for heart rate with Fridericia's formula (QTcF = QT/RR^0.33 where RR is 60/heart rate).
Measured: up to 11 days
Change from baseline up to end of study in heart rate
Standard 12-lead electrocardiograms will be recorded at rest with the subject in the supine position for at least a 5-minute period at various time points throughout the study.
Measured: up to 11 days
Number of subjects with treatment-emergent electrocardiogram abnormalities
Standard 12-lead electrocardiograms will be recorded at rest with the subject in the supine position for at least a 5-minute period at various time points throughout the study. Treatment-emergent electrocardiogram abnormalities are defined as abnormalities occurring after study drug administration up to end of study and which were not observed either at pre-dose or screening.
Measured: up to 11 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2015 (estimated)
- Study startDec 2011
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Martine Géhin, PhD, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02381496
- Sponsor's protocol ID
- AC-072-101
- Status last verified
- Jul 2018
- First submitted
- 3 Mar 2015
- Last updated
- 10 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
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 Three-part Study to Assess the Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Ascending Single Doses (Including Food Interaction) of ACT-453859 in Healthy Male Subjects, of Ascending Multiple Doses of ACT-453859 in Healthy Male and Female Subjects, and of Multiple Doses of Setipiprant (ACT-129968) in Healthy Male and Female Subjects
- ClinicalTrials.gov ID
- NCT02381496
- Acronym / sponsor ID
- AC-072-101
- Conditions
- Healthy
- Keywords
- ACT-453859, ACT-463036, Setipiprant, Tolerability, safety, pharmacodynamics, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- Dec 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 6 Mar 2015 (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.
This is a three-part study to assess the tolerability, safety, pharmacodynamics, and pharmacokinetics of ascending single doses (including food interaction) of ACT-453859 in healthy male subjects, of ascending multiple doses of ACT-453859 in healthy male and female subjects, and of multiple doses of setipiprant (ACT-129968) in healthy male and female subjects.
Detailed description
Part A of this study is a single-center, randomized, double-blind, placebo-controlled, single-ascending dose (SAD) design in healthy male subjects. In each cohort, eight subjects will be randomized as follows:
- Six male subjects will receive a single oral dose of ACT-453859, under fasted conditions.
- Two male subjects will receive matching placebo, under fasted conditions.
The doses of ACT-453859 were 1, 3, 10, 30, 100, 300, and 800 mg. Subjects in only one cohort (100 mg dose cohort) will come back for a second period of treatment under fed conditions.
Part B is a single-center, randomized, double-blind, placebo-controlled multiple-ascending dose (MAD) design in healthy male and female of subjects.
In each of 3 cohorts, eight subjects will be randomized to receive multiple doses of ACT-453859 or placebo once a day for 7 days as follows:
- Three male subjects will receive ACT-453859.
- Three female subjects will receive ACT-453859.
- One male subject will receive matching placebo.
- One female subject will receive matching placebo.
The doses of ACT-453859 will be 10, 100, and 800 mg per day.
Part C is a single-center and open-label design consisting of multiple oral doses of setipiprant given in a sequential design in healthy male and female subjects.
Eight subjects will be randomized to receive multiple doses of setipiprant for 7 days (only a single dose on Day 7), in Treatment Period I (TPI) and Treatment Period II (TPII), as follows:
- Four male subjects will receive setipiprant 500 mg twice a day (b.i.d.) in TPI and 1000 mg b.i.d. in TPII.
- Four female subjects will receive setipiprant 500 mg b.i.d. in TPI and 1000 mg b.i.d. in TPII.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Part A: Cohort A1: ACT-453859 1 mg | Experimental | Drug: ACT-453859 1 mg, Other: PlaceboACT-453859 1 mg or placebo, single dose, administered orally in the fasted state * Six male subjects will receive ACT-453859 * Two male subjects will receive matching placebo |
| Part A: Cohort A2: ACT-453859 3 mg | Experimental | Drug: ACT-453859 3 mg, Other: PlaceboACT-453859 3 mg or placebo, single dose, administered orally in the fasted state * Six male subjects will receive ACT-453859 * Two male subjects will receive matching placebo |
| Part A: Cohort A3: ACT-453859 10 mg | Experimental | Drug: ACT-453859 10 mg, Other: PlaceboACT-453859 10 mg or placebo, single dose, administered orally in the fasted state * Six male subjects will receive ACT-453859 * Two male subjects will receive matching placebo |
| Part A: Cohort A4: ACT-453859 30 mg | Experimental | Drug: ACT-453859 30mg, Other: PlaceboACT-453859 30 mg or placebo, single dose, administered orally in the fasted state * Six male subjects will receive ACT-453859 * Two male subjects will receive matching placebo |
| Part A: Cohort A5: ACT-453859 100 mg | Experimental | Drug: ACT-453859 100 mg, Other: PlaceboACT-453859 100 mg or placebo, single dose, administered orally in the fasted state * Six male subjects will receive ACT-453859 * Two male subjects will receive matching placebo After a washout period of 10-20 days subjects will return for a second study period to receive the same treatment received in the first session but under fed conditions |
| Part A: Cohort A6: ACT-453859 300 mg | Experimental | Drug: ACT-453859 300 mg, Other: PlaceboACT-453859 300 mg or placebo, single dose, administered orally in the fasted state * Six male subjects will receive ACT-453859 * Two male subjects will receive matching placebo |
| Part A: Cohort A7: ACT-453859 800 mg | Experimental | Drug: ACT-453859 800 mg, Other: PlaceboACT-453859 800 mg or placebo, single dose, administered orally in the fasted state * Six male subjects will receive ACT-453859 * Two male subjects will receive matching placebo |
| Part B: Cohort B1: ACT-453859 10 mg | Experimental | Drug: ACT-453859 10 mg, Other: PlaceboACT-453859 10 mg or placebo, once a day for 7 days, administered orally in the fasted state * Three male subjects will receive ACT-453859 * Three female subjects will receive ACT-453859 * One male subject will receive matching placebo * One female subject will receive matching placebo |
| Part B: Cohort B2: ACT-453859 100 mg | Experimental | Drug: ACT-453859 100 mg, Other: PlaceboACT-453859 100 mg or placebo, once a day for 7 days, administered orally in the fasted state * Three male subjects will receive ACT-453859 * Three female subjects will receive ACT-453859 * One male subject will receive matching placebo * One female subject will receive matching placebo |
| Part B: Cohort B3: ACT-453859 800 mg | Experimental | Drug: ACT-453859 800 mg, Other: PlaceboACT-453859 800 mg, once a day for 7 days, administered orally in the fasted state * Three male subjects will receive ACT-453859 * Three female subjects will receive ACT-453859 * One male subject will receive matching placebo * One female subject will receive matching placebo |
| Part C: Treatment Periods I & II: Setipiprant | Experimental | Drug: Setipiprant 500 mg, Drug: Setipiprant 1000 mgSetipiprant 500 mg, twice daily for 7 days, administered orally in Treatment Period I (TPI) and setipiprant 1000 mg, twice daily for 7 days, administered orally in Treatment Period II (TPII) * Four male subjects will receive setipiprant 500 mg twice a day in TPI and 1000 mg twice a day in TPII. * Four female subjects will receive setipiprant 500 mg twice a day in TPI and 1000 mg twice a day in TPII. There will be a washout period of 10 days between TPI and TPII |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Signed informed consent.
- Healthy male subjects (Part A), healthy male and female subjects for Parts B \& C.
- Hematology, coagulation (Part A and Part B only), clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent.
- No clinically significant findings on physical examination.
- Body mass index between 18.0 and 28.0 kg/m^2.
Key exclusion criteria (19 listed)
- Previous history of fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions.
- Veins unsuitable for intravenous puncture on either arm.
- Treatment with any prescribed or over-the-counter medications within 2 weeks prior to first study drug administration.
- Treatment or substances known to inhibit cytochrome P (CYP) enzyme drug metabolism .
- Treatment or substances known to induce CYP enzyme drug metabolism.
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 |
|---|---|---|
| ACT-453859 1 mgCapsule | Drug | Part A: Cohort A1: ACT-453859 1 mg |
| ACT-453859 3 mgCapsule | Drug | Part A: Cohort A2: ACT-453859 3 mg |
| ACT-453859 10 mgCapsule | Drug | Part A: Cohort A3: ACT-453859 10 mg, Part B: Cohort B1: ACT-453859 10 mg |
| ACT-453859 30mgCapsule | Drug | Part A: Cohort A4: ACT-453859 30 mg |
| ACT-453859 100 mgCapsule | Drug | Part A: Cohort A5: ACT-453859 100 mg, Part B: Cohort B2: ACT-453859 100 mg |
| ACT-453859 300 mgCapsule | Drug | Part A: Cohort A6: ACT-453859 300 mg |
| ACT-453859 800 mgCapsule | Drug | Part A: Cohort A7: ACT-453859 800 mg, Part B: Cohort B3: ACT-453859 800 mg |
| PlaceboMatching ACT-453859 placebo capsule | Other | Part A: Cohort A1: ACT-453859 1 mg, Part A: Cohort A2: ACT-453859 3 mg, Part A: Cohort A3: ACT-453859 10 mg, Part A: Cohort A4: ACT-453859 30 mg, Part A: Cohort A5: ACT-453859 100 mg, Part A: Cohort A6: ACT-453859 300 mg, Part A: Cohort A7: ACT-453859 800 mg, Part B: Cohort B1: ACT-453859 10 mg, Part B: Cohort B2: ACT-453859 100 mg, Part B: Cohort B3: ACT-453859 800 mg |
| Setipiprant 500 mgCapsule | Drug | Part C: Treatment Periods I & II: Setipiprant |
| Setipiprant 1000 mgCapsule | Drug | Part C: Treatment Periods I & II: Setipiprant |
Primary outcome
Area under the plasma concentration-time curve (AUC(0-t)) for single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. AUC(0-t) will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification (LOQ).
AUC(0-t) for the active metabolite ACT-463036 after single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. AUC(0-t) will be calculated according to the linear trapezoidal rule using the measured concentration-time values above the LOQ.
Area under the plasma concentration-time curve (AUC(0-infinity)) for single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. 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 LOQ and λZ represents the terminal elimination rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
AUC(0-infinity) for the active metabolite ACT-463036 after single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. 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 LOQ and λZ represents the terminal elimination rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
Time to reach maximum plasma concentration (tmax) for single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-453859 will be used to directly obtain tmax.
tmax for the active metabolite ACT-463036 after single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-463036 will be used to directly obtain tmax.
Terminal elimination rate constant (λZ) for single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. λZ will be determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
λZ for the active metabolite ACT-463036 after single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. λZ will be determined by log-linear regression analysis of the measured plasma concentrations of the terminal elimination phase.
Plasma half life (t1/2) for single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. t1/2 will be calculated as follows: t½ = ln 2/λZ.
t1/2 for the active metabolite ACT-463036 after single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. t1/2 will be calculated as follows: t½ = ln 2/λZ.
Maximum plasma concentration (Cmax) for single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-453859 will be used to directly obtain Cmax.
Cmax for the active metabolite ACT-463036 after single doses of ACT-453859
Time frame: 72 hours
Blood samples for pharmacokinetic assessments will be collected at various time points over the study period. The measured individual plasma concentrations of ACT-463036 will be used to directly obtain Cmax.
Renal clearance (CLR) following single dose of ACT-453859 100 mg
Time frame: 72 hours
Urine samples for pharmacokinetic assessments will be collected at various time points over the study period. CLR will be calculated by dividing the total amount of unchanged ACT-453859 excreted in urine during the collection interval by AUC(0-t).
Percentage of ACT-453859 excreted unchanged in the urine following single dose of ACT-453859 100 mg
Time frame: 72 hours
Urine samples for pharmacokinetic assessments will be collected at various time points over the study period.The percentage of total dose excreted unchanged in urine will be calculated by the total amount excreted, divided by the dose administered, multiplied by 100.
27 secondary outcomes
Area under the plasma concentration-time curve (AUCτ) for multiple doses of ACT-453859 (Day 1 & Day 7)
Time frame: 11 days
AUCτ for the active metabolite ACT-463036 after multiple doses of ACT-453859 (Day 1 & Day 7)
Time frame: 11 days
Cmax for multiple doses of ACT-453859 (Day 1 & Day 7)
Time frame: 11 days
Cmax for the active metabolite ACT-463036 after multiple doses of ACT-453859 (Day 1 & Day 7)
Time frame: 11 days
tmax for multiple doses of ACT-453859 (Day 1 & Day 7)
Time frame: 11 days
tmax for the active metabolite ACT-463036 after multiple doses of ACT-453859 (Day 1 & Day 7)
Time frame: 11 days
λZ for multiple doses of ACT-453859
Time frame: 11 days
λZ for the active metabolite ACT-463036 after multiple doses of ACT-453859
Time frame: 11 days
t1/2 for multiple doses of ACT-453859
Time frame: 11 days
t1/2 for the active metabolite ACT-463036 after multiple doses of ACT-453859
Time frame: 11 days
CLR following multiple doses of ACT-453859 100 mg per day
Time frame: 8 days
Percentage of ACT-453859 excreted unchanged in the urine following multiple doses of ACT-453859 100 mg per day
Time frame: 8 days
AUCτ for setipiprant after multiple doses of 500 and 1000 mg b.i.d. setipiprant (Day 1 & Day 7)
Time frame: 10 days
Cmax for setipiprant after multiple doses of 500 and 1000 mg b.i.d. setipiprant (Day 1 & Day 7)
Time frame: 10 days
tmax for setipiprant after multiple doses of 500 and 1000 mg b.i.d. setipiprant (Day 1 & Day 7)
Time frame: 10 days
Chemoattractant receptor-homologous molecule expressed on T helper 2 cells (CRTH2) antagonist pharmacodynamic (PD) effect after single doses of ACT-453859
Time frame: 72 hours
CRTH2 antagonist PD effect after multiple doses of ACT-453859
Time frame: 10 days
CRTH2 antagonist PD effect after multiple doses of setipiprant
Time frame: 10 days
CRTH2 antagonist potency following administration of single and multiple doses of ACT-453859 and setipiprant
Time frame: up to 10 days
Change from baseline up to end of study in systolic blood pressure
Time frame: up to 11 days
Change from baseline up to end of study in diastolic blood pressure
Time frame: up to 11 days
Change from baseline up to end of study in heart rate
Time frame: up to 11 days
Change from baseline up to end of study in QT interval (Time interval from beginning of the Q wave until end of the T wave)
Time frame: up to 11 days
Change from baseline up to end of study in QTcB interval (QT interval corrected for heart rate according to Bazett's correction)
Time frame: up to 11 days
Change from baseline up to end of study in QTcF interval (QT interval corrected for heart rate according to Fridericia's correction)
Time frame: up to 11 days
Change from baseline up to end of study in heart rate
Time frame: up to 11 days
Number of subjects with treatment-emergent electrocardiogram abnormalities
Time frame: up to 11 days
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.
Martine Géhin, PhD study director
Actelion
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ACT-453859 1 mg, ACT-453859 3 mg and ACT-453859 10 mg in people with Healthy, run by Idorsia Pharmaceuticals Ltd..
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 14 inclusion and 19 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.
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?
Area under the plasma concentration-time curve (AUC(0-t)) for single doses of ACT-453859 (time frame: 72 hours). The study lists 14 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.