Healthy SubjectsPhase 1NCT02919319
A Single Ascending Dose Study of ACT-541468 in Healthy Male Subjects
A Phase 1 study testing ACT-541468 (Formulation A), ACT-541468 (Formulation B) and 14C-labeled ACT-541468 in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Netherlands.
Trial summary
The main objectives of this first-into-man study were to investigate the safety, tolerability and the pharmacokinetic profile of single oral doses of ACT-541468 in healthy male adults. Pharmacodynamic effects (through a battery of Central Nervous System tests) were also assessed. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- ACT-541468 (Formulation A), ACT-541468 (Formulation B) and 14C-labeled ACT-541468
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Feb 2015to 1 May 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed informed consent prior to any study-mandated procedure.
- Males aged from 18 to 45 years (inclusive) at screening.
- Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
- Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) between 100-145 mmHg, 50-90 mmHg and 45-90 bpm (all inclusive) at screening, respectively.
- Healthy on the basis of physical examination,electrocardiogram and laboratory tests.
Who cannot join
- Known hypersensitivity to any excipients of the drug formulations.
- History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs.
- History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0 at screening.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, Pharmacodynamics, Absolute Bioavailability, Mass Balance, and Metabolism of ACT-541468 in Healthy Male Subjects
The main objectives of this first-into-man study were to investigate the safety, tolerability and the pharmacokinetic profile of single oral doses of ACT-541468 in healthy male adults. Pharmacodynamic effects (through a battery of Central Nervous System tests) were also assessed.
Read the detailed description
The study consisted of ascending dose groups; each dose group was investigated in a new group of 8 healthy male subjects (6 on active drug and 2 on placebo). In addition, the study included a biocomparison part (dose group 2), an absolute bioavailability part (dose group 4), and a mass balance / metabolism part (dose group 3).
- Conditions
- Healthy Subjects
- Being tested
- ACT-541468 (Formulation A), ACT-541468 (Formulation B), Placebo (Formulation A), Placebo (Formulation B), 14C-labeled ACT-541468
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACT-541468 (Formulation A)Drug
Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg
ACT-541468 (Formulation B)Drug
Soft gelatin capsules for oral administration formulated at the strength of 25 mg
Placebo (Formulation A)Drug
Hard capsules matching ACT-541468 Formulation A
Placebo (Formulation B)Drug
Soft capsules matching ACT-541468 Formulation B
14C-labeled ACT-541468Drug
Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously
Placebo tracerDrug
Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration.
| Study group | Role | What they receive |
|---|---|---|
| Dose group 1 | Experimental | Six subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. Receives: Drug: ACT-541468 (Formulation A); Drug: Placebo (Formulation A) |
| Dose group 2 | Experimental | Three subjects received a single oral dose (25 mg) of ACT-541468 formulation A during Period 1 and a single oral dose (25 mg) of ACT-541468 formulation B during Period 2. Three other subjects Subjects received ACT-541468 formulation B during Period 1 and ACT-541468 formulation A during Period 2. Two additional subjects received the matching placebos in both treatment periods. Receives: Drug: ACT-541468 (Formulation A); Drug: ACT-541468 (Formulation B); Drug: Placebo (Formulation A); Drug: Placebo (Formulation B) |
| Dose group 3 | Experimental | Six subjects received 50 mg of ACT-541468 (formulation A) as a single oral dose in combination with a [14C]-ACT-541468 oral tracer for the mass balance and metabolism analyses. Two other subjects received the matching placebos. Receives: Drug: ACT-541468 (Formulation A); Drug: Placebo (Formulation A); Drug: 14C-labeled ACT-541468; Drug: Placebo tracer |
| Dose group 4 | Experimental | Six subjects received 100 mg of ACT-541468 (formulation A) as a single oral dose in combination with a [14C]-ACT-541468 intravenous tracer for the absolute bioavailability assessment. Two other subjects received the matching placebos. Receives: Drug: ACT-541468 (Formulation A); Drug: Placebo (Formulation A); Drug: 14C-labeled ACT-541468; Drug: Placebo tracer |
| Dose group 5 | Experimental | Six subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. Receives: Drug: ACT-541468 (Formulation A); Drug: Placebo (Formulation A) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with treatment-emergent adverse events and serious adverse events
Collection of any adverse event at each dose level
Measured: Day 8
Secondary outcomes (6)
Maximum plasma concentration (Cmax) of ACT-541468
Cmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level
Measured: From pre-dose up to 168 hours post-dose
Time to reach Cmax (tmax) of ACT-541468
tmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level
Measured: From pre-dose up to 168 hours post-dose
Terminal half-life (t1/2) of ACT-541468
t1/2 was calculated from the terminal rate constant obtained from the plasma concentrations-time curves of ACT-541468, at each dose level
Measured: From pre-dose up to 168 hours post-dose
Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468
AUC(0-inf) is the area under the plasma concentration-time curves of ACT-541468, calculated from time 0 (pre-dose) to extrapolated infinite time, at each dose level
Measured: From pre-dose up to 168 hours post-dose
Percentage of dose excreted in feces and urine
Percentage of oral dose of 14C-labeled ACT-541468 excreted in feces (FPE), urine (UPE) and both, as determined in the dose group 3
Measured: From pre-dose up to 168 hours post-dose
Absolute bioavailability (F) of ACT-541468
Absolute bioavailability was determined for dose group 4 and defined as the ratio of AUC(0-inf) after oral administration of ACT-541468 and after intravenous infusion of 14C-labeled ACT-541468 (tracer)
Measured: Up to 96 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2016 (estimated)
- Study start1 Feb 2015
- Primary completion1 May 2015
- Study completion1 May 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy SubjectsStudies 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, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clemens Muehlan, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02919319
- Sponsor's protocol ID
- AC-078-101
- Other IDs
- 2014-003129-16, 2014
- Status last verified
- Jul 2018
- First submitted
- 28 Sep 2016
- Last updated
- 10 Jul 2018
- Results posted
- 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-controlled, Randomized, Single Ascending Dose Study to Investigate the Tolerability, Safety, Pharmacokinetics, Pharmacodynamics, Absolute Bioavailability, Mass Balance, and Metabolism of ACT-541468 in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02919319
- Acronym / sponsor ID
- AC-078-101
- Conditions
- Healthy Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Feb 2015 (actual)
- Primary completion
- 1 May 2015 (actual)
- Study completion
- 1 May 2015 (actual)
- First posted
- 29 Sep 2016 (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 main objectives of this first-into-man study were to investigate the safety, tolerability and the pharmacokinetic profile of single oral doses of ACT-541468 in healthy male adults. Pharmacodynamic effects (through a battery of Central Nervous System tests) were also assessed.
Detailed description
The study consisted of ascending dose groups; each dose group was investigated in a new group of 8 healthy male subjects (6 on active drug and 2 on placebo). In addition, the study included a biocomparison part (dose group 2), an absolute bioavailability part (dose group 4), and a mass balance / metabolism part (dose group 3).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose group 1 | Experimental | Drug: ACT-541468 (Formulation A), Drug: Placebo (Formulation A)Six subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. |
| Dose group 2 | Experimental | Drug: ACT-541468 (Formulation A), Drug: ACT-541468 (Formulation B), Drug: Placebo (Formulation A), Drug: Placebo (Formulation B)Three subjects received a single oral dose (25 mg) of ACT-541468 formulation A during Period 1 and a single oral dose (25 mg) of ACT-541468 formulation B during Period 2. Three other subjects Subjects received ACT-541468 formulation B during Period 1 and ACT-541468 formulation A during Period 2. Two additional subjects received the matching placebos in both treatment periods. |
| Dose group 3 | Experimental | Drug: ACT-541468 (Formulation A), Drug: Placebo (Formulation A), Drug: 14C-labeled ACT-541468, Drug: Placebo tracerSix subjects received 50 mg of ACT-541468 (formulation A) as a single oral dose in combination with a [14C]-ACT-541468 oral tracer for the mass balance and metabolism analyses. Two other subjects received the matching placebos. |
| Dose group 4 | Experimental | Drug: ACT-541468 (Formulation A), Drug: Placebo (Formulation A), Drug: 14C-labeled ACT-541468, Drug: Placebo tracerSix subjects received 100 mg of ACT-541468 (formulation A) as a single oral dose in combination with a [14C]-ACT-541468 intravenous tracer for the absolute bioavailability assessment. Two other subjects received the matching placebos. |
| Dose group 5 | Experimental | Drug: ACT-541468 (Formulation A), Drug: Placebo (Formulation A)Six subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Signed informed consent prior to any study-mandated procedure.
- Males aged from 18 to 45 years (inclusive) at screening.
- Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening.
- Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) between 100-145 mmHg, 50-90 mmHg and 45-90 bpm (all inclusive) at screening, respectively.
- Healthy on the basis of physical examination,electrocardiogram and laboratory tests.
Key exclusion criteria (4 listed)
- Known hypersensitivity to any excipients of the drug formulations.
- History or presence of any disease or condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study drugs.
- History of narcolepsy or cataplexy or modified Swiss narcolepsy scale total score < 0 at screening.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.
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-541468 (Formulation A)Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg | Drug | Dose group 1, Dose group 2, Dose group 3, Dose group 4, Dose group 5 |
| ACT-541468 (Formulation B)Soft gelatin capsules for oral administration formulated at the strength of 25 mg | Drug | Dose group 2 |
| Placebo (Formulation A)Hard capsules matching ACT-541468 Formulation A | Drug | Dose group 1, Dose group 2, Dose group 3, Dose group 4, Dose group 5 |
| Placebo (Formulation B)Soft capsules matching ACT-541468 Formulation B | Drug | Dose group 2 |
| 14C-labeled ACT-541468Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously | Drug | Dose group 3, Dose group 4 |
| Placebo tracerSterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration. | Drug | Dose group 3, Dose group 4 |
Primary outcome
Number of subjects with treatment-emergent adverse events and serious adverse events
Time frame: Day 8
Collection of any adverse event at each dose level
6 secondary outcomes
Maximum plasma concentration (Cmax) of ACT-541468
Time frame: From pre-dose up to 168 hours post-dose
Time to reach Cmax (tmax) of ACT-541468
Time frame: From pre-dose up to 168 hours post-dose
Terminal half-life (t1/2) of ACT-541468
Time frame: From pre-dose up to 168 hours post-dose
Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468
Time frame: From pre-dose up to 168 hours post-dose
Percentage of dose excreted in feces and urine
Time frame: From pre-dose up to 168 hours post-dose
Absolute bioavailability (F) of ACT-541468
Time frame: Up to 96 hours post-dose
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.
Related trials for Healthy Subjects
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Not yet recruitingObservational study
Establishment of Biobank of Nasal Epithelium Samples From Healthy Volunteers
Healthy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
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.
Clemens Muehlan 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-541468 (Formulation A), ACT-541468 (Formulation B) and 14C-labeled ACT-541468 in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 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?
Number of subjects with treatment-emergent adverse events and serious adverse events (time frame: Day 8). 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.