Healthy SubjectsPhase 1NCT03165097
Study to Evaluate Safety and Tolerability of ACT-709478 in Healthy Subjects
A Phase 1 study testing ACT-709478, Midazolam and ACT-709478 combined with midazolam in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
Trial summary
The primary purpose of this study is to evaluate the safety and tolerability of ascending multiple doses of ACT-709478 in healthy male and female subjects Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- ACT-709478, Midazolam and ACT-709478 combined with midazolam
- 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
- 46 participants
- Where
- 1 siteGermany
- Study dates
- 7 Jul 2017to 28 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed informed consent form
- Healthy male and female subjects aged between 18 and 55 years (inclusive) at screening
- Negative serum pregnancy tests at screening and negative urine pregnancy test at Day -1 for women and agreement to use 2 reliable methods of contraception for at least 3 months after last study drug administration
- Body mass index of 18.0 to 29.9 kg/m2 (inclusive) at screening
- Systolic blood pressure 100-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 bpm (inclusive), measured after 5 minutes in the supine position at screening and on Day -1
- Healthy on the basis of physical examination, cardiovascular, ophthalmological, neurological assessments and laboratory tests
Who cannot join
- Known hypersensitivity to ACT-709478 or drugs of the same class, or any of their excipients
- 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 treatments
- QT interval corrected with Fridericia's formula (QTcF) > 450 ms (using the ECG machine HR correction method) at screening and on Day -1
- Treatment with another investigational treatment within 2 months or 5 t1/2 (whichever is the longest) prior to screening or participation in more than four investigational treatment studies within 1 year prior to screening
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Double-blind, Parallel-group, Randomized, Placebo-controlled, Multiple-ascending Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-709478 in Healthy Subjects
The primary purpose of this study is to evaluate the safety and tolerability of ascending multiple doses of ACT-709478 in healthy male and female subjects
- Conditions
- Healthy Subjects
- Being tested
- ACT-709478, Placebo, Midazolam, ACT-709478 combined with midazolam
- Keywords
- tolerability, safety
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACT-709478Drug
Hard gelatine capsules for oral administration
PlaceboDrug
Placebo capsules matching ACT-709478 capsules
MidazolamDrug
Midazolam oral solution (2 mg/mL) applied with a syringe
ACT-709478 combined with midazolamDrug
Hard gelatine capsules for oral administration (ACT-709478) to be taken first followed by Midazolam oral solution (2 mg/mL) applied with a syringe
| Study group | Role | What they receive |
|---|---|---|
| ACT-709478 | Experimental | 40 subjects will receive multiple doses of ACT-709478 at the planned dose levels of 30, 60, 100, and 200 mg.
Each dose level will be investigated in a new cohort of 10 healthy male and female subjects (4 male subjects on active drug and 1 on placebo, 4 female subjects on active drug and 1 on placebo) undergoing one treatment period with a once daily dosing scheme. Receives: Drug: ACT-709478 |
| Placebo | Placebo comparator | Matched placebo administered accordingly Receives: Drug: Placebo |
| Midazolam | Other | 4 mg taken by mouth on Day 1 of the corresponding cohort Receives: Drug: Midazolam |
| ACT-709478 combined with Midazolam | Experimental | On Day 22 and Day 30, midazolam (4 mg) and ACT-709478 (60 mg or 100 mg) to be co-administered. Receives: Drug: ACT-709478 combined with midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events
The percentage of subjects with treatment-emergent adverse events will be reported
Measured: up to Day 23
Changes from baseline in vital signs
Vital signs include diastolic and systolic blood pressure and pulse rate
Measured: up to Day 23
Incidence of any clinical relevant findings in ECG variables
The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported
Measured: up to Day 23
Secondary outcomes (7)
Maximum plasma concentration (Cmax) of ACT-709478
Cmax is derived from the observed plasma concentration-time curves
Measured: up to Day 23
Time to reach Cmax (tmax) of ACT-709478
tmax is directly derived from the observed plasma concentrations
Measured: up to Day 23
Terminal half-life (t1/2) of ACT-709478
t1/2 is calculated from the terminal rate constant obtained from the plasma concentrations-time curves
Measured: up to Day 23
Area under the plasma concentration-time curve AUC(tau) of ACT-709478
AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval
Measured: up to Day 23
Area under the plasma concentration-time curve AUC(tau) of midazolam
AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval
Measured: 24 hours after dosing on Day 1, Day 22 and Day 30
Time to reach Cmax (tmax)
tmax is directly derived from the observed plasma concentrations
Measured: 24 hours after dosing on Day 1, Day 22 and Day 30
Maximum plasma concentration (Cmax) of ACT-709478
Cmax is derived from the observed plasma concentration-time curves
Measured: 24 hours after dosing on Day 1, Day 22 and Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2017
- Study start7 Jul 2017
- Primary completion15 Nov 2018
- Study completion28 Dec 2018
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 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Idorsia Pharmaceuticals Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03165097
- Sponsor's protocol ID
- AC-083-102
- Other IDs
- 2017-000336-34, 2017
- Status last verified
- Dec 2019
- First submitted
- 23 May 2017
- Last updated
- 24 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Richard M, Kaufmann P, Ort M, Kornberger R, Dingemanse J. Multiple-Ascending Dose Study in Healthy Subjects to Assess the Pharmacokinetics, Tolerability, and CYP3A4 Interaction Potential of the T-Type Calcium Channel Blocker ACT-709478, A Potential New Antiepileptic Drug. CNS Drugs. 2020 Mar;34(3):311-323. doi: 10.1007/s40263-019-00697-1.
PubMed 31994022
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Double-blind, Parallel-group, Randomized, Placebo-controlled, Multiple-ascending Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-709478 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03165097
- Acronym / sponsor ID
- AC-083-102
- Conditions
- Healthy Subjects
- Keywords
- tolerability, safety
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 7 Jul 2017 (actual)
- Primary completion
- 15 Nov 2018 (actual)
- Study completion
- 28 Dec 2018 (actual)
- First posted
- 24 May 2017 (actual)
- 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 purpose of this study is to evaluate the safety and tolerability of ascending multiple doses of ACT-709478 in healthy male and female subjects
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ACT-709478 | Experimental | Drug: ACT-70947840 subjects will receive multiple doses of ACT-709478 at the planned dose levels of 30, 60, 100, and 200 mg. Each dose level will be investigated in a new cohort of 10 healthy male and female subjects (4 male subjects on active drug and 1 on placebo, 4 female subjects on active drug and 1 on placebo) undergoing one treatment period with a once daily dosing scheme. |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo administered accordingly |
| Midazolam | Other | Drug: Midazolam4 mg taken by mouth on Day 1 of the corresponding cohort |
| ACT-709478 combined with Midazolam | Experimental | Drug: ACT-709478 combined with midazolamOn Day 22 and Day 30, midazolam (4 mg) and ACT-709478 (60 mg or 100 mg) to be co-administered. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Signed informed consent form
- Healthy male and female subjects aged between 18 and 55 years (inclusive) at screening
- Negative serum pregnancy tests at screening and negative urine pregnancy test at Day -1 for women and agreement to use 2 reliable methods of contraception for at least 3 months after last study drug administration
- Body mass index of 18.0 to 29.9 kg/m2 (inclusive) at screening
- Systolic blood pressure 100-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 bpm (inclusive), measured after 5 minutes in the supine position at screening and on Day -1
Key exclusion criteria (5 listed)
- Known hypersensitivity to ACT-709478 or drugs of the same class, or any of their excipients
- 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 treatments
- QT interval corrected with Fridericia's formula (QTcF) > 450 ms (using the ECG machine HR correction method) at screening and on Day -1
- Treatment with another investigational treatment within 2 months or 5 t1/2 (whichever is the longest) prior to screening or participation in more than four investigational treatment studies within 1 year prior to screening
- Any circumstances or conditions, which, in the opinion of the investigator, may affect 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-709478Hard gelatine capsules for oral administration | Drug | ACT-709478 |
| PlaceboPlacebo capsules matching ACT-709478 capsules | Drug | Placebo |
| MidazolamMidazolam oral solution (2 mg/mL) applied with a syringe | Drug | Midazolam |
| ACT-709478 combined with midazolamHard gelatine capsules for oral administration (ACT-709478) to be taken first followed by Midazolam oral solution (2 mg/mL) applied with a syringe | Drug | ACT-709478 combined with Midazolam |
Primary outcome
Incidence of treatment-emergent adverse events
Time frame: up to Day 23
The percentage of subjects with treatment-emergent adverse events will be reported
Changes from baseline in vital signs
Time frame: up to Day 23
Vital signs include diastolic and systolic blood pressure and pulse rate
Incidence of any clinical relevant findings in ECG variables
Time frame: up to Day 23
The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported
7 secondary outcomes
Maximum plasma concentration (Cmax) of ACT-709478
Time frame: up to Day 23
Time to reach Cmax (tmax) of ACT-709478
Time frame: up to Day 23
Terminal half-life (t1/2) of ACT-709478
Time frame: up to Day 23
Area under the plasma concentration-time curve AUC(tau) of ACT-709478
Time frame: up to Day 23
Area under the plasma concentration-time curve AUC(tau) of midazolam
Time frame: 24 hours after dosing on Day 1, Day 22 and Day 30
Time to reach Cmax (tmax)
Time frame: 24 hours after dosing on Day 1, Day 22 and Day 30
Maximum plasma concentration (Cmax) of ACT-709478
Time frame: 24 hours after dosing on Day 1, Day 22 and Day 30
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 24 Dec 2019.
- Derived from this study: PubMed 31994022Richard M, Kaufmann P, Ort M, Kornberger R, Dingemanse J. Multiple-Ascending Dose Study in Healthy Subjects to Assess the Pharmacokinetics, Tolerability, and CYP3A4 Interaction Potential of the T-Type Calcium Channel Blocker ACT-709478, A Potential New Antiepileptic Drug. CNS Drugs. 2020 Mar;34(3):311-323. doi: 10.1007/s40263-019-00697-1.
- Individual participant dataSharing planned: No
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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.
Study Director 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-709478, Midazolam and ACT-709478 combined with midazolam in people with Healthy Subjects, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
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 6 inclusion and 5 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 24 Dec 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 Germany. 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. Some participants in this study may receive a placebo. 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?
Incidence of treatment-emergent adverse events (time frame: up to Day 23). The study lists 3 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 NCT03165097, 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 24 Dec 2019.