SafetyPhase 1NCT01954589
Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-462206
A Phase 1 study testing ACT-462206 5 mg, ACT-462206 25 mg and ACT-462206 100mg in people with Safety and Tolerability, run by Idorsia Pharmaceuticals Ltd. at 1 site in Netherlands.
Trial summary
A study of ACT-462206 to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamic of ascending single doses of ACT-462206, a novel dual orexin receptor antagonist in healthy male subjects. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Safety, Tolerability, Pharmacodynamics
- What is being tested?
- ACT-462206 5 mg, ACT-462206 25 mg and ACT-462206 100mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2011to Jan 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
- Healthy male subjects aged between 18 and 45 years (inclusive) at screening
- Hematology, clinical chemistry, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening
- No clinically significant findings on physical examination at screening
- Body mass index between 18.0 and 28.0 kg/m^2 (inclusive) at screening
- Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 45-90 beats per minute (inclusive) measured at screening on the dominant arm (dominant arm is the writing arm) after 5 min in supine position
- 12-lead electrocardiogram without clinically relevant abnormalities in the supine position at screening
- 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.
Who cannot join
- Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
- 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)
- Treatment with any prescribed medications (including vaccines) or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to (first) study drug administration
- Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening
- History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening
- 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
Show all 15Show fewer
- Excessive caffeine consumption, defined as ≥ 800 mg per day at screening of caffeine)
- Smoking within 3 months prior to screening 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, at screening
- Positive results from the human immunodeficiency virus serology at screening
- Known hypersensitivity to any excipients of the drug formulations
- Modified Swiss Narcolepsy Scale total score < 0 or history of narcolepsy or cataplexy
- Any circumstances or conditions, which, in the opinion of the investigator, might 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: Double-blind, Placebo- and Active-controlled, Randomized, Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-462206 in Healthy Male Subjects
A study of ACT-462206 to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamic of ascending single doses of ACT-462206, a novel dual orexin receptor antagonist in healthy male subjects.
Read the detailed description
Each dose level will be investigated in a new group of eight healthy male subjects (six on active drug and two on placebo). Each subject will participate in one treatment period, with the exception of subjects in the crossover part (i.e., almorexant reference group at the fourth dose level), who will participate in two treatment periods. At this dose level subjects on active drug (six) will receive in one treatment period ACT-462206 and in the other 400 mg of almorexant; subjects on placebo (two) will receive the corresponding placebos (double-dummy).
- Conditions
- Safety, Tolerability, Pharmacodynamics, Pharmacokinetics
- Being tested
- ACT-462206 5 mg, ACT-462206 25 mg, ACT-462206 100mg, ACT-462206 200mg, ACT-462206 400mg
- Keywords
- ACT-462206, Selective dual orexin receptor antagonist
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACT-462206 5 mgDrug
ACT-462206 25 mgDrug
ACT-462206 100mgDrug
ACT-462206 200mgDrug
ACT-462206 400mgDrug
ACT-462206 1000 mgDrug
ACT-462206 1500mgDrug
Almorexant 400mgDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| ACT-462206 5 mg/Placebo | Experimental | 6 subjects received a single, 5 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo Receives: Drug: ACT-462206 5 mg; Drug: Placebo |
| ACT-462206 25 mg/Placebo | Experimental | 6 subjects received a single, 25 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo Receives: Drug: ACT-462206 25 mg; Drug: Placebo |
| ACT-462206 100mg/Placebo | Experimental | 6 subjects received a single, 100 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo Receives: Drug: ACT-462206 100mg; Drug: Placebo |
| ACT-462206 200mg/Almorexant 400mg/Placebo | Experimental | Subjects were assigned to one of two possible treatment sequences: A/B or B/A with a washout period of 14 days between treatment periods.
Treatment A: Single oral dose of ACT-462206 200 mg or placebo. Treatment B: Single oral dose of almorexant 400 mg or placebo. In each sequence 6 subjects received ACT-462206 or almorexant \& 2 subjects received placebo Receives: Drug: ACT-462206 200mg; Drug: Almorexant 400mg; Drug: Placebo |
| Experimental: ACT-462206 400mg/Placebo | Experimental | 6 subjects received a single, 400 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo Receives: Drug: ACT-462206 400mg; Drug: Placebo |
| ACT-462206 1000 mg | Experimental | 6 subjects received a single, 1000 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo Receives: Drug: ACT-462206 1000 mg; Drug: Placebo |
| ACT-462206 1500mg/Placebo | Experimental | 6 subjects received a single, 1500 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo Receives: Drug: ACT-462206 1500mg; Drug: Placebo |
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 was measured on the dominant arm using an automatic oscillometric device. Measurements were taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm was used for all measurements. Measurements were taken at 1, 3, 5, 8, 24, 48, 72 and 96 hours post-dose.
Measured: 96 hours
Change in supine diastolic blood pressure from baseline up to the end of study
Blood pressure was measured on the dominant arm using an automatic oscillometric device. Measurements were taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm was used for all measurements. Measurements were taken at 1, 3, 5, 8, 24, 48, 72 and 96 hours post-dose.
Measured: 96 hours
Change in heart rate from baseline up to the end of study
Heart rate was measured on the dominant arm using an automatic oscillometric device. The dominant (writing) arm was used for all measurements. Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Measured: 96 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: 96 hours
Change in PR Interval from baseline up to the end of study
A standard 12-lead electrocardiogram (ECG) was recorded in supine position after a 5-min rest period. The PR interval is the time interval from the beginning of the P wave to the beginning of the QRS complex. Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Measured: 96 hours
Change in QRS Interval from baseline up to the end of study
A standard 12-lead ECG was 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 were taken at 1, 3, 5, 8, and 96 hours post-dose.
Measured: 96 hours
Change in QTcB Interval from baseline up to the end of study
A standard 12-lead ECG was recorded in supine position after a 5-min rest period. The QTcB interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5 where RR is 60/heart rate). Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Measured: 96 hours
Change in QTcF Interval from baseline up to the end of study
A standard 12-lead ECG was recorded in supine position after a 5-min rest period. The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcF = QT/RR^0.33 where RR is 60/heart rate). Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Measured: 96 hours
Change in saccadic peak velocity from baseline up to the end of study
Recording of eye movements was performed in a quiet room with ambient illumination, with only 1 subject present. A microcomputer system was used for recording \& analysis. Disposable electrodes were applied on the forehead \& beside the lateral canthi of both eyes for registration of the electro-oculographic signals. Head movements were restricted using a fixed head support. The target consisted of a moving dot displayed on a computer screen, fixed in front of the head support. Saccadic eye movements were recorded for stimulus amplitudes of approximately 15 degrees to either side. Fifteen saccades were recorded with inter-stimulus intervals varying randomly between 3 and 6 s. Average values of saccadic peak velocity of all correct saccades were used as variables.Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Measured: 10 hours
Change in performance on adaptive tracking from baseline up to the end of study
The adaptive tracking test was performed using customized equipment and software, following a standard protocol. Adaptive tracking is a pursuit-tracking task. The subject was asked to keep a dot inside a randomly moving circle by operating a joystick. If successful, the speed of the moving circle was increased. Conversely, the velocity was reduced if the subject could not maintain the dot inside the circle. The average performance (%) and the standard deviation of scores during a 3.5-min assessment period were used for analysis. The assessment period included a run-in time of 0.5 min, during which data were not recorded.Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Measured: 10 hours
Change in body sway from baseline up to the end of study
Body sway was assessed using a body sway meter. All body movements during a 2-min period of time were integrated and expressed as mm sway on a digital display. Measurements of body sway were made in the sagittal (forward/backward) planes by positioning of the subject relative to the apparatus, with a string attached to the waist. The contribution of vision to postural control was eliminated by asking subjects to close their eyes. Subjects were instructed to wear the same pair of comfortable, low-heeled shoes in each session. Before starting a measurement, subjects were asked to stand still and comfortable, with their feet approximately 10 cm apart and their hands in a relaxed position alongside the body. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Measured: 10 hours
Change in visual analogue scale (VAS) score to assess alertness from baseline up to the end of study
Dutch versions of the VAS according to Bond and Lader (British Journal of Medical Psychology 1974;47:211-18) were used to assess subjective alertness. At each time point of assessment, the subject indicated (with a mouse click on the computer screen) how he felt, on sixteen dimension horizontal VAS. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Measured: 10 hours
Change in VAS score to assess mood from baseline up to the end of study
Dutch versions of the VAS according to Bond and Lader (British Journal of Medical Psychology 1974;47:211-18) were used to assess subjective mood. At each time point of assessment, the subject indicated (with a mouse click on the computer screen) how he felt, on sixteen dimension horizontal VAS. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Measured: 10 hours
Change in VAS score to assess calmness from baseline up to the end of study
Dutch versions of the VAS according to Bond and Lader (British Journal of Medical Psychology 1974;47:211-18) were used to assess subjective calmness. At each time point of assessment, the subject indicated (with a mouse click on the computer screen) how he felt, on sixteen dimension horizontal VAS. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Measured: 10 hours
Secondary outcomes (6)
Maximum plasma concentration (Cmax) of ACT-462206
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with ACT-462206, and at 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 24 hours, 36 hours, 48 hours, 72 hours, and 96 hours after dosing. Cmax calculated on the basis of the blood sampling time points.
Measured: 96 hours
Time to reach maximum plasma concentration (tmax) of ACT-462206
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with ACT-462206, and at 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 24 hours, 36 hours, 48 hours, 72 hours, and 96 hours after dosing. tmax calculated on the basis of the blood sampling time points.
Measured: 96 hours
Area under the plasma concentration-time curve (AUC) from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of ACT-462206
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with ACT-462206, and at 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 24 hours, 36 hours, 48 hours, 72 hours, and 96 hours after dosing. AUC0-t was 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: 96 hours
AUC from time zero to infinity (AUC0-∞) of ACT-462206
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with ACT-462206, and at 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 24 hours, 36 hours, 48 hours, 72 hours, and 96 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: 96 hours
AUC from time zero to 8 hours after administration (AUC0-8) of ACT-462206
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with ACT-462206, and at 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, and 8 hours, after dosing. AUC0-8 was calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification.
Measured: 8 hours
AUC from time zero to 24 hours after administration (AUC0-24) of ACT-462206
Blood samples for pharmacokinetic analysis taken immediately prior to dosing with ACT-462206, and at 10 minutes, 20 minutes, 30 minutes, 45 minutes, 60 minutes, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, and 24 hours after dosing. AUC0-24 was calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startNov 2011
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SafetyStudies 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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Petra Baecker, MD, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01954589
- Sponsor's protocol ID
- AC-074-101
- Status last verified
- Jul 2018
- First submitted
- 27 Sep 2013
- 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
- Double-blind, Placebo- and Active-controlled, Randomized, Single-ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of ACT-462206 in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT01954589
- Acronym / sponsor ID
- AC-074-101
- Conditions
- Safety, Tolerability, Pharmacodynamics, Pharmacokinetics
- Keywords
- ACT-462206, Selective dual orexin receptor antagonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 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.
A study of ACT-462206 to evaluate the tolerability, safety, pharmacokinetics, and pharmacodynamic of ascending single doses of ACT-462206, a novel dual orexin receptor antagonist in healthy male subjects.
Detailed description
Each dose level will be investigated in a new group of eight healthy male subjects (six on active drug and two on placebo). Each subject will participate in one treatment period, with the exception of subjects in the crossover part (i.e., almorexant reference group at the fourth dose level), who will participate in two treatment periods. At this dose level subjects on active drug (six) will receive in one treatment period ACT-462206 and in the other 400 mg of almorexant; subjects on placebo (two) will receive the corresponding placebos (double-dummy).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| ACT-462206 5 mg/Placebo | Experimental | Drug: ACT-462206 5 mg, Drug: Placebo6 subjects received a single, 5 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo |
| ACT-462206 25 mg/Placebo | Experimental | Drug: ACT-462206 25 mg, Drug: Placebo6 subjects received a single, 25 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo |
| ACT-462206 100mg/Placebo | Experimental | Drug: ACT-462206 100mg, Drug: Placebo6 subjects received a single, 100 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo |
| ACT-462206 200mg/Almorexant 400mg/Placebo | Experimental | Drug: ACT-462206 200mg, Drug: Almorexant 400mg, Drug: PlaceboSubjects were assigned to one of two possible treatment sequences: A/B or B/A with a washout period of 14 days between treatment periods. Treatment A: Single oral dose of ACT-462206 200 mg or placebo. Treatment B: Single oral dose of almorexant 400 mg or placebo. In each sequence 6 subjects received ACT-462206 or almorexant \& 2 subjects received placebo |
| Experimental: ACT-462206 400mg/Placebo | Experimental | Drug: ACT-462206 400mg, Drug: Placebo6 subjects received a single, 400 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo |
| ACT-462206 1000 mg | Experimental | Drug: ACT-462206 1000 mg, Drug: Placebo6 subjects received a single, 1000 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo |
| ACT-462206 1500mg/Placebo | Experimental | Drug: ACT-462206 1500mg, Drug: Placebo6 subjects received a single, 1500 mg, oral dose of ACT-462206 and 2 subjects received a single, oral dose of placebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Healthy male subjects aged between 18 and 45 years (inclusive) at screening
- Hematology, clinical chemistry, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening
- No clinically significant findings on physical examination at screening
- Body mass index between 18.0 and 28.0 kg/m^2 (inclusive) at screening
- Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 45-90 beats per minute (inclusive) measured at screening on the dominant arm (dominant arm is the writing arm) after 5 min in supine position
Key exclusion criteria (15 listed)
- Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
- 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)
- Treatment with any prescribed medications (including vaccines) or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to (first) study drug administration
- Treatment with another investigational drug within 3 months prior to screening or having participated in more than four investigational drug studies within 1 year prior to screening
- History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening
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-462206 5 mg | Drug | ACT-462206 5 mg/Placebo |
| ACT-462206 25 mg | Drug | ACT-462206 25 mg/Placebo |
| ACT-462206 100mg | Drug | ACT-462206 100mg/Placebo |
| ACT-462206 200mg | Drug | ACT-462206 200mg/Almorexant 400mg/Placebo |
| ACT-462206 400mg | Drug | Experimental: ACT-462206 400mg/Placebo |
| ACT-462206 1000 mg | Drug | ACT-462206 1000 mg |
| ACT-462206 1500mg | Drug | ACT-462206 1500mg/Placebo |
| Almorexant 400mg | Drug | ACT-462206 200mg/Almorexant 400mg/Placebo |
| Placebo | Drug | ACT-462206 1000 mg, ACT-462206 100mg/Placebo, ACT-462206 1500mg/Placebo, ACT-462206 200mg/Almorexant 400mg/Placebo, ACT-462206 25 mg/Placebo, ACT-462206 5 mg/Placebo, Experimental: ACT-462206 400mg/Placebo |
Primary outcome
Change in supine systolic blood pressure from baseline up to the end of study
Time frame: 96 hours
Blood pressure was measured on the dominant arm using an automatic oscillometric device. Measurements were taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm was used for all measurements. Measurements were taken at 1, 3, 5, 8, 24, 48, 72 and 96 hours post-dose.
Change in supine diastolic blood pressure from baseline up to the end of study
Time frame: 96 hours
Blood pressure was measured on the dominant arm using an automatic oscillometric device. Measurements were taken with the subject in the supine position after a resting period of at least 5 min. The dominant (writing) arm was used for all measurements. Measurements were taken at 1, 3, 5, 8, 24, 48, 72 and 96 hours post-dose.
Change in heart rate from baseline up to the end of study
Time frame: 96 hours
Heart rate was measured on the dominant arm using an automatic oscillometric device. The dominant (writing) arm was used for all measurements. Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Change in body weight from baseline up to the end of study
Time frame: 96 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 PR Interval from baseline up to the end of study
Time frame: 96 hours
A standard 12-lead electrocardiogram (ECG) was recorded in supine position after a 5-min rest period. The PR interval is the time interval from the beginning of the P wave to the beginning of the QRS complex. Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Change in QRS Interval from baseline up to the end of study
Time frame: 96 hours
A standard 12-lead ECG was 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 were taken at 1, 3, 5, 8, and 96 hours post-dose.
Change in QTcB Interval from baseline up to the end of study
Time frame: 96 hours
A standard 12-lead ECG was recorded in supine position after a 5-min rest period. The QTcB interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5 where RR is 60/heart rate). Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Change in QTcF Interval from baseline up to the end of study
Time frame: 96 hours
A standard 12-lead ECG was recorded in supine position after a 5-min rest period. The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcF = QT/RR^0.33 where RR is 60/heart rate). Measurements were taken at 1, 3, 5, 8, and 96 hours post-dose.
Change in saccadic peak velocity from baseline up to the end of study
Time frame: 10 hours
Recording of eye movements was performed in a quiet room with ambient illumination, with only 1 subject present. A microcomputer system was used for recording \& analysis. Disposable electrodes were applied on the forehead \& beside the lateral canthi of both eyes for registration of the electro-oculographic signals. Head movements were restricted using a fixed head support. The target consisted of a moving dot displayed on a computer screen, fixed in front of the head support. Saccadic eye movements were recorded for stimulus amplitudes of approximately 15 degrees to either side. Fifteen saccades were recorded with inter-stimulus intervals varying randomly between 3 and 6 s. Average values of saccadic peak velocity of all correct saccades were used as variables.Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Change in performance on adaptive tracking from baseline up to the end of study
Time frame: 10 hours
The adaptive tracking test was performed using customized equipment and software, following a standard protocol. Adaptive tracking is a pursuit-tracking task. The subject was asked to keep a dot inside a randomly moving circle by operating a joystick. If successful, the speed of the moving circle was increased. Conversely, the velocity was reduced if the subject could not maintain the dot inside the circle. The average performance (%) and the standard deviation of scores during a 3.5-min assessment period were used for analysis. The assessment period included a run-in time of 0.5 min, during which data were not recorded.Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Change in body sway from baseline up to the end of study
Time frame: 10 hours
Body sway was assessed using a body sway meter. All body movements during a 2-min period of time were integrated and expressed as mm sway on a digital display. Measurements of body sway were made in the sagittal (forward/backward) planes by positioning of the subject relative to the apparatus, with a string attached to the waist. The contribution of vision to postural control was eliminated by asking subjects to close their eyes. Subjects were instructed to wear the same pair of comfortable, low-heeled shoes in each session. Before starting a measurement, subjects were asked to stand still and comfortable, with their feet approximately 10 cm apart and their hands in a relaxed position alongside the body. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Change in visual analogue scale (VAS) score to assess alertness from baseline up to the end of study
Time frame: 10 hours
Dutch versions of the VAS according to Bond and Lader (British Journal of Medical Psychology 1974;47:211-18) were used to assess subjective alertness. At each time point of assessment, the subject indicated (with a mouse click on the computer screen) how he felt, on sixteen dimension horizontal VAS. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Change in VAS score to assess mood from baseline up to the end of study
Time frame: 10 hours
Dutch versions of the VAS according to Bond and Lader (British Journal of Medical Psychology 1974;47:211-18) were used to assess subjective mood. At each time point of assessment, the subject indicated (with a mouse click on the computer screen) how he felt, on sixteen dimension horizontal VAS. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
Change in VAS score to assess calmness from baseline up to the end of study
Time frame: 10 hours
Dutch versions of the VAS according to Bond and Lader (British Journal of Medical Psychology 1974;47:211-18) were used to assess subjective calmness. At each time point of assessment, the subject indicated (with a mouse click on the computer screen) how he felt, on sixteen dimension horizontal VAS. Measurements were taken at 20 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, and 10 hours post-dose.
6 secondary outcomes
Maximum plasma concentration (Cmax) of ACT-462206
Time frame: 96 hours
Time to reach maximum plasma concentration (tmax) of ACT-462206
Time frame: 96 hours
Area under the plasma concentration-time curve (AUC) from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of ACT-462206
Time frame: 96 hours
AUC from time zero to infinity (AUC0-∞) of ACT-462206
Time frame: 96 hours
AUC from time zero to 8 hours after administration (AUC0-8) of ACT-462206
Time frame: 8 hours
AUC from time zero to 24 hours after administration (AUC0-24) of ACT-462206
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.
Petra Baecker, MD study director
Actelion
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-462206 5 mg, ACT-462206 25 mg and ACT-462206 100mg in people with Safety and Tolerability, run by Idorsia Pharmaceuticals Ltd. at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in supine systolic blood pressure from baseline up to the end of study (time frame: 96 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.