HealthyPhase 1NCT02186002
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-451840 in Healthy Subjects (Part A)
A Phase 1 study testing ACT-451840 10 mg, ACT-451840 50 mg and ACT-451840 200 mg in people with Healthy, run by Idorsia Pharmaceuticals Ltd. at 1 site in France.
Trial summary
The primary objective of the study was to evaluate the safety and tolerability of ACT-451840 in healthy male subjects.Secondary objectives were : to investigate the pharmacokinetics (PK) of ACT-451840; to investigate the effect of food on the PK of ACT-451840; to evaluate the urinary excretion of ACT-451840 and to… 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
- What is being tested?
- ACT-451840 10 mg, ACT-451840 50 mg and ACT-451840 200 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteFrance
- 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 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.
- Body mass index (BMI) of 18.0 to 28.0 kg/m2 (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 min in the supine position at screening.
- 12-lead electrocardiogram without clinically relevant abnormalities, measured after 5 min in the supine position at screening.
- Hematology, coagulation, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
- No clinically significant findings on the physical examination at screening.
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- Negative results from urine drug screen at screening.
- Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.
- Subject covered by Health Insurance system and/or in compliance with the recommendations of the National Law in force relating to biomedical research.
- If the subject's partner could become pregnant, reliable methods of contraception must be used from the time of the first administration of study medication until 3 months following administration of the last dose of study medication.
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 might interfere with the absorption, distribution, metabolism or excretion of the study drug.
- Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
- Documented history of chronic liver or gall bladder disease.
- Documented history of hemolytic anemia.
- Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture).
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- Previous exposure to the study medication.
- Treatment with another investigational drug within 3 months prior to screening or participation in more than four investigational drug studies within the 12 months prior to screening.
- Subject in the exclusion period of a previous clinical study.
- Subject who had received more than 4,500 Euros as indemnities for his participation in a biomedical research within the 12 last months, including the indemnities for the present study.
- History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
- Excessive caffeine consumption, defined as 800 mg or more 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) within 2 weeks prior to first study drug administration.
- Loss of 250 mL or more of blood within 3 months prior to screening.
- Positive results from the hepatitis (hepatitis B and C) serology, except for vaccinated subjects.
- Positive results from 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.
About this study
Official title: Single-center, Double-blind, Placebo-controlled, Randomized, Single-ascending Dose, With Nested Cross-over for Food Effect, to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-451840 in Healthy Subjects (Part A)
The primary objective of the study was to evaluate the safety and tolerability of ACT-451840 in healthy male subjects.Secondary objectives were : to investigate the pharmacokinetics (PK) of ACT-451840; to investigate the effect of food on the PK of ACT-451840; to evaluate the urinary excretion of ACT-451840 and to investigate the antimalarial activity of ACT-451840.
- Conditions
- Healthy
- Being tested
- ACT-451840 10 mg, ACT-451840 50 mg, ACT-451840 200 mg, ACT-451840 500 mg, ACT-451840 1000 mg
- Keywords
- ACT-451840, Safety, Tolerability, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACT-451840 10 mgDrug
ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water
ACT-451840 50 mgDrug
ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water
ACT-451840 200 mgDrug
ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water
ACT-451840 500 mgDrug
ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water
ACT-451840 1000 mgDrug
ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water
ACT-451840 (Dose to be determined)Drug
ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | A single oral dose of 10 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. Receives: Drug: ACT-451840 10 mg; Drug: Placebo |
| Group 2 | Experimental | A single oral dose of 50 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 50 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. Receives: Drug: ACT-451840 50 mg; Drug: Placebo |
| Group 3 | Experimental | A single oral dose of 200 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 200 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. Receives: Drug: ACT-451840 200 mg; Drug: Placebo |
| Group 4 | Experimental | A single dose of 500 mg ACT-451840 or placebo to be administered to subjects in the fasted state, followed by an observation period of 4 days. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 500 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. Receives: Drug: ACT-451840 500 mg; Drug: Placebo |
| Group 5 | Experimental | A single oral dose of 1000 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 1000 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. Receives: Drug: ACT-451840 1000 mg; Drug: Placebo |
| Group 6 | Experimental | A single oral dose of ACT-451840 or placebo to be administered to subjects in the fed state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. The dose of ACT-451840 to be determined on the basis of the pharmacokinetic results for the previous groups Receives: Drug: ACT-451840 (Dose to be determined); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in systolic blood pressure from baseline up to end of study
Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.
Measured: 4 days
Change in diastolic blood pressure from baseline up to end of study
Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.
Measured: 4 days
Change in pulse rate from baseline up to end of study
Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.
Measured: 4 days
Change in body weight from baseline up to 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: 4 days
Change in heart rate from baseline up to end of study
Heart rate will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
Measured: 4 days
Change in PQ/PR interval from baseline up to end of study
PQ/PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
Measured: 4 days
Change in QRS interval from baseline up to end of study
QRS interval (time interval from the beginning of the Q wave to the end of the S wave) will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
Measured: 4 days
Change in QTc interval (time interval from beginning of the Q wave until end of the T wave) according to Fridericia's correction (QTcF interval) from baseline up to end of study
QTcF interval will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing. The QTcF interval is the QTc interval corrected for heart rate with Fridericia's formula (QTcB = QT/RR^0.33 where RR is 60/heart rate)
Measured: 4 days
Change in QTc interval (time interval from beginning of the Q wave until end of the T wave) according to Bazett's correction (QTcB interval) from baseline up to end of study
QTcB interval will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing. The QTcB interval is the QTc interval corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5 where RR is 60/heart rate).
Measured: 4 days
Number of treatment-emergent electrocardiogram abnormalities from baseline up to end of study
Treatment-emergent electrocardiogram abnormalities will be identified using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
Measured: 4 days
Secondary outcomes (8)
Maximum plasma concentration (Cmax) of ACT-451840
Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-451840 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 96 hours after dosing.
Cmax will be calculated on the basis of the blood sampling time points.
Measured: 4 days
Time to maximum plasma concentration (tmax) of ACT-451840
Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-451840 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 96 hours after dosing.
tmax will be calculated on the basis of the blood sampling time points.
Measured: 4 days
Area under the plasma concentration-time curve (AUC(0-t)) of ACT-451840
Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-451840 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 96 hours after dosing.
AUC(0-t) will be calculated as the area under the plasma concentration-time profile from time zero to time t of the last measured concentration above the limit of quantification.
Measured: 4 days
Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-451840
Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-451840 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 96 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: 4 days
Plasma half life (t1/2) of ACT-451840
Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-451840 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 96 hours after dosing.
t1/2 will be calculated on the basis of the blood sampling time points.
Measured: 4 days
Dose proportionality of single doses of ACT-451840
Blood samples for pharmacokinetic analysis will be taken immediately prior to dosing with ACT-451840 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24, 36, 48, 72, and 96 hours after dosing.
Dose proportionality will be explored by the power model as described by Gough et al [1995]. The power model will be applied to the loge AUC0-∞ and Cmax data. A point estimate and 90% Confidence Interval (CI) will be produced for the population mean slope. Approximate dose proportionality will be concluded if the 90% CI for the slope is completely contained in the range (1+log(0.5))/log(r), 1+log(2)/log(r) where r = high dose/low dose.
Measured: 4 days
Percentage of administered ACT-451840 excreted unchanged in urine
A baseline urine sample will be collected from each subject in the selected dose group after admission on Day -1. On Day 1, subjects will be instructed to empty their bladder immediately prior to study drug intake. Thereafter, all urine produced will be collected during the 4 days following study drug intake until the morning of Day 5. On Day 1, urine will be collected at three consecutive 8-hour intervals, from 0-8 hours, 8-16 hours, and 16-24 hours. On Days 2, 3, and 4 urine will be collected in 24-hours intervals.
Measured: 4 days
Anti-malarial half-maximal inhibitory concentration (IC50) of ACT-451840
Blood (2.5 mL) will be collected by direct venipuncture or via an intravenous catheter placed in an antecubital vein in the arm into 3.5 mL vacutainer serum separation tubes. The anti-malarial IC50 of ACT-451840 will be determined using a bioassay and ACT-451840 IC50 concentrations will be estimated based on the measured antimalarial activity.
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2014 (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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Idorsia Pharmaceuticals Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02186002
- Sponsor's protocol ID
- AC-071-101
- Status last verified
- Aug 2019
- First submitted
- 8 Jul 2014
- Last updated
- 9 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Bruderer S, Hurst N, de Kanter R, Miraval T, Pfeifer T, Donazzolo Y, Dingemanse J. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity. Antimicrob Agents Chemother. 2015 Feb;59(2):935-42. doi: 10.1128/AAC.04125-14. Epub 2014 Nov 24.
PubMed 25421475
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-center, Double-blind, Placebo-controlled, Randomized, Single-ascending Dose, With Nested Cross-over for Food Effect, to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-451840 in Healthy Subjects (Part A)
- ClinicalTrials.gov ID
- NCT02186002
- Acronym / sponsor ID
- AC-071-101
- Conditions
- Healthy
- Keywords
- ACT-451840, Safety, Tolerability, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 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
- 10 Jul 2014 (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.
The primary objective of the study was to evaluate the safety and tolerability of ACT-451840 in healthy male subjects.Secondary objectives were : to investigate the pharmacokinetics (PK) of ACT-451840; to investigate the effect of food on the PK of ACT-451840; to evaluate the urinary excretion of ACT-451840 and to investigate the antimalarial activity of ACT-451840.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: ACT-451840 10 mg, Drug: PlaceboA single oral dose of 10 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. |
| Group 2 | Experimental | Drug: ACT-451840 50 mg, Drug: PlaceboA single oral dose of 50 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 50 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. |
| Group 3 | Experimental | Drug: ACT-451840 200 mg, Drug: PlaceboA single oral dose of 200 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 200 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. |
| Group 4 | Experimental | Drug: ACT-451840 500 mg, Drug: PlaceboA single dose of 500 mg ACT-451840 or placebo to be administered to subjects in the fasted state, followed by an observation period of 4 days. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 500 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. |
| Group 5 | Experimental | Drug: ACT-451840 1000 mg, Drug: PlaceboA single oral dose of 1000 mg ACT-451840 or placebo to be administered to subjects in the fasted state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. If indicated by the pharmacokinetic data obtained in the preceding groups and if not previously performed, a food effect investigation will be conducted after a washout period of at least 7 days. A dose of 1000 mg ACT-451840 or placebo is to be administered to subjects in the fed state, followed by the second observation period of 4 days. Six subjects who received ACT-451810 in the fasted state are to receive ACT-451840 in the fed state and 2 subjects who received placebo in the fasted state to receive matching placebo in the fed state. |
| Group 6 | Experimental | Drug: ACT-451840 (Dose to be determined), Drug: PlaceboA single oral dose of ACT-451840 or placebo to be administered to subjects in the fed state. Six subjects are to receive ACT-451840 and 2 subjects to receive matching placebo. The dose of ACT-451840 to be determined on the basis of the pharmacokinetic results for the previous groups |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Signed informed consent in the local language prior to any study-mandated procedure.
- Body mass index (BMI) of 18.0 to 28.0 kg/m2 (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 min in the supine position at screening.
- 12-lead electrocardiogram without clinically relevant abnormalities, measured after 5 min in the supine position at screening.
- Hematology, coagulation, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
Key exclusion criteria (19 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 might interfere with the absorption, distribution, metabolism or excretion of the study drug.
- Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
- Documented history of chronic liver or gall bladder disease.
- Documented history of hemolytic anemia.
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-451840 10 mgACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water | Drug | Group 1 |
| ACT-451840 50 mgACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water | Drug | Group 2 |
| ACT-451840 200 mgACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water | Drug | Group 3 |
| ACT-451840 500 mgACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water | Drug | Group 4 |
| ACT-451840 1000 mgACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water | Drug | Group 5 |
| ACT-451840 (Dose to be determined)ACT-451840 was provided as dry powder, which was reconstituted as a suspension with 25 mL of tap water | Drug | Group 6 |
| Placebo | Drug | Group 1, Group 2, Group 3, Group 4, Group 5, Group 6 |
Primary outcome
Change in systolic blood pressure from baseline up to end of study
Time frame: 4 days
Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.
Change in diastolic blood pressure from baseline up to end of study
Time frame: 4 days
Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.
Change in pulse rate from baseline up to end of study
Time frame: 4 days
Blood pressure (systolic and diastolic) and pulse rate will be measured using an automatic oscillometric device, always on the dominant/same arm (i.e., dominant arm right = writing with right hand). Measurements should be recorded from the subject in the supine position after having rested for a 5-minute period.
Change in body weight from baseline up to end of study
Time frame: 4 days
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 heart rate from baseline up to end of study
Time frame: 4 days
Heart rate will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
Change in PQ/PR interval from baseline up to end of study
Time frame: 4 days
PQ/PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
Change in QRS interval from baseline up to end of study
Time frame: 4 days
QRS interval (time interval from the beginning of the Q wave to the end of the S wave) will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
Change in QTc interval (time interval from beginning of the Q wave until end of the T wave) according to Fridericia's correction (QTcF interval) from baseline up to end of study
Time frame: 4 days
QTcF interval will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing. The QTcF interval is the QTc interval corrected for heart rate with Fridericia's formula (QTcB = QT/RR^0.33 where RR is 60/heart rate)
Change in QTc interval (time interval from beginning of the Q wave until end of the T wave) according to Bazett's correction (QTcB interval) from baseline up to end of study
Time frame: 4 days
QTcB interval will be measured using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing. The QTcB interval is the QTc interval corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5 where RR is 60/heart rate).
Number of treatment-emergent electrocardiogram abnormalities from baseline up to end of study
Time frame: 4 days
Treatment-emergent electrocardiogram abnormalities will be identified using a standard 12-lead electrocardiogram recorded at rest with the subject in the supine position for a 5-minute period. Electrocardiograms will be performed immediately prior to dosing and at 1, 2, 4, 6, 8, 12, 24, 48, and 96 hours post dosing.
8 secondary outcomes
Maximum plasma concentration (Cmax) of ACT-451840
Time frame: 4 days
Time to maximum plasma concentration (tmax) of ACT-451840
Time frame: 4 days
Area under the plasma concentration-time curve (AUC(0-t)) of ACT-451840
Time frame: 4 days
Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-451840
Time frame: 4 days
Plasma half life (t1/2) of ACT-451840
Time frame: 4 days
Dose proportionality of single doses of ACT-451840
Time frame: 4 days
Percentage of administered ACT-451840 excreted unchanged in urine
Time frame: 4 days
Anti-malarial half-maximal inhibitory concentration (IC50) of ACT-451840
Time frame: 4 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 9 Aug 2019.
- Derived from this study: PubMed 25421475Bruderer S, Hurst N, de Kanter R, Miraval T, Pfeifer T, Donazzolo Y, Dingemanse J. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity. Antimicrob Agents Chemother. 2015 Feb;59(2):935-42. doi: 10.1128/AAC.04125-14. Epub 2014 Nov 24.
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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.
Clinical Trials study director
Idorsia Pharmaceuticals Ltd.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ACT-451840 10 mg, ACT-451840 50 mg and ACT-451840 200 mg in people with Healthy, run by Idorsia Pharmaceuticals Ltd. at 1 site in France.
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 10 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 9 Aug 2019. 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 systolic blood pressure from baseline up to end of study (time frame: 4 days). 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?
On the ClinicalTrials.gov record for NCT02186002, which also lists 1 linked publication.
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 9 Aug 2019.