Clinical Trial Results:
A Phase 2a, multi-center, single-blind, within-subject, placebo-controlled study to assess the pharmacodynamics of ACT-709478 in subjects with photosensitive epilepsy
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Summary
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EudraCT number |
2017-000494-36 |
Trial protocol |
DE FR |
Global end of trial date |
25 Apr 2018
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Results information
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Results version number |
v1 |
This version publication date |
25 May 2019
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First version publication date |
25 May 2019
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AC-083-103
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT03239691 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Idorsia Pharmaceuticals Ltd
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Sponsor organisation address |
Hegenheimermattweg 91, Allschwil, Switzerland, 4123
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Public contact |
Clinical Trial Disclosure Desk, Idorsia Pharmaceuticals Ltd, clinical-trials-disclosure@idorsia.com
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Scientific contact |
Clinical Trial Disclosure Desk, Idorsia Pharmaceuticals Ltd, clinical-trials-disclosure@idorsia.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Nov 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Apr 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the pharmacodynamics by means of the change in intermittent photic stimulation induced photoparoxysmal response in male and female subjects with photosensitive epilepsy following single dose administration of ACT-709478.
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Protection of trial subjects |
Prior to the start of the study and implementation of the amendments, Independent Ethics Committees were consulted, i.e., review panels that were responsible for ensuring the protection of the rights, safety, and well being of human subjects involved in a clinical investigation.
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Background therapy |
Subjects were allowed to be on stable background treatment (i.e., no dose changes within 4 weeks prior to screening and no changes foreseen during the study) with a maximum of 2 concomitant antiepileptic drugs. During the whole study duration, they received the antiepileptic drugs according to their regular administration schedule. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Oct 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in 2 countries and 5 sites | ||||||||||
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Pre-assignment
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Screening details |
A screening evaluation was performed within 3–28 days before first study treatment administration for male subjects and female subjects of non-childbearing potential and within 10–28 days before first study treatment administration for female subjects of childbearing potential. | ||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Single blind | ||||||||||
Roles blinded |
Subject | ||||||||||
Blinding implementation details |
For safety reasons, this study was conducted in a single-blind fashion. The investigator and study site personnel, the monitors, and the sponsor knew on which study days placebo or ACT-709478 was administered. In contrast, the subjects remained blinded to the study treatment until study closure. The investigational treatment and its matching placebo were indistinguishable.
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Arms
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Arm title
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ACT-709478 single-dose / placebo administration | ||||||||||
Arm description |
Each subject was to receive both placebo and a single dose of active treatment on consecutive days. Placebo was to be administered in the morning of Day 1 and Day 3, and ACT-709478 in the morning of Day 2. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
ACT-709478
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Hard gelatin capsules for oral administration formulated at a strength of 100 mg.
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Matching placebo available as matching capsules for oral administration.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ACT-709478 single-dose / placebo administration
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Reporting group description |
Each subject was to receive both placebo and a single dose of active treatment on consecutive days. Placebo was to be administered in the morning of Day 1 and Day 3, and ACT-709478 in the morning of Day 2. | ||
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End point title |
Positive response described as complete suppression of photoparoxysmal response or a clinically relevant reduction in the standardized photosensitive range [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From Day 2 to Day 10
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time (hours) to onset of positive response | ||||||||
End point description |
Defined by the first time point after ACT-709478 administration at which complete suppression of PPR or reduction in SPR ≥ 3 units compared to baseline is achieved at least at 2 consecutive time points.
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End point type |
Secondary
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End point timeframe |
From Day 2 to Day 10
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration (hours) of positive response | ||||||||
End point description |
Defined as the time elapsed between the time point of onset of the positive response and the last time point of the positive response after ACT-709478 administration
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End point type |
Secondary
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End point timeframe |
From Day 2 to Day 10
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum SPR reduction | ||||||||
End point description |
Defined as the largest reduction in SPR achieved at any time point compared to baseline during the positive response after ACT-709478 administration
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End point type |
Secondary
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End point timeframe |
From Day 2 to Day 10
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| No statistical analyses for this end point | |||||||||
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End point title |
Time (hours) to maximum SPR reduction | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From Day 2 to Day 10
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events treatment-emergent for placebo (from placebo administration on Day 1 up to ACT-709478 administration on Day 2) and ACT-709478 (from ACT-709478 administration on Day 2 up to EOS).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
ACT-709478
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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12 Jul 2017 |
Amendment 1 was a substantial amendment finalized before the start of the clinical conduct of the study. This amendment was issued in response to two requests expressed by BfArM:
1) The inclusion of the submission of a protocol amendment in the procedure to continue the study, e.g., with an intermediate dose, if a stopping criterion is met for dose escalation.
2) The C-SSRS was added in order to exclude subjects with a history of suicidal thoughts or attempted suicide and to monitor the subjects for signs of suicidal thoughts or suicidal behavior during the course of the study.
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28 Nov 2017 |
Amendment 2 specified the change of sponsorship of the study from Actelion Pharmaceuticals Ltd to Idorsia Pharmaceuticals Ltd, effective from 1 March 2018 |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to the late occurrence, the positive response in one subject was not considered relevant. | |||
