Clinical Trial Results:
An open-label, Phase IIa, multi-center, 12-week prospective study to evaluate the safety and efficacy of NOE-105 at a daily dose range of 2.5mg to 15mg in adult and adolescent male patients with Tourette Syndrome (TS).
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Summary
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EudraCT number |
2021-004424-15 |
Trial protocol |
DE |
Global end of trial date |
03 Nov 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Nov 2024
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First version publication date |
24 Nov 2024
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Other versions |
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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 |
NOE-TTS-211
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
ANZCTR: ACTRN12621000319875 | ||
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Sponsors
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Sponsor organisation name |
Noema Pharma Australia Pty Ltd,
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Sponsor organisation address |
109 Pitt Street, Sydney, Australia,
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Public contact |
Clinical Trials, Noema Pharma, clinicaltrials@noemapharma.com
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Scientific contact |
Clinical Trials, Noema Pharma, clinicaltrials@noemapharma.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 |
13 Jun 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Nov 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Nov 2023
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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 identify the optimal dose range of NOE-105 that is associated with tic control in adult and adolescent patients with TS.
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Protection of trial subjects |
Staggered recruitment of adolescent patients according to patient age, starting with a sentinel cohort of patients of at least 15 years of age.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
23 Jun 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Australia: 11
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Country: Number of subjects enrolled |
Germany: 4
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Worldwide total number of subjects |
15
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EEA total number of subjects |
4
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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) |
2
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Adults (18-64 years) |
13
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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 |
- | ||||||||||||
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Pre-assignment
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Screening details |
Subjects underwent screening and baseline assessments were recorded up to 28 days before dosing. A signed written ICF was obtained prior to all screening assessments. | ||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
16 [1] | ||||||||||||
Number of subjects completed |
15 | ||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Consent withdrawn by subject: 1 | ||||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One patient was screened and signed an ICF, but did not meet the inclusion criterion 1 (“Ability and willingness to provide written informed consent and to comply with the study procedures”) |
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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NOE-105 Treatment | ||||||||||||
Arm description |
Single arm of the study, dose escalation from 2.5 mg once daily to a maximum of 15 mg once daily. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
gemlapodect
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Investigational medicinal product code |
NOE-105
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Dosage escalation from 2.5 mg to 15 mg daily over the duration of the study.
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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 |
NOE-105 Treatment
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Reporting group description |
Single arm of the study, dose escalation from 2.5 mg once daily to a maximum of 15 mg once daily. | ||
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End point title |
“Response” as assessed by the RAC, and reported using the 7-category TS-CGI-C scale. [1] | ||||||||||
End point description |
Following the Week 12 End of study visit, patient data from those with at least on post treatment assessment were reviewed by the RAC to adjudicate the treatment response using the TS-CGI-C scale. In total, 8/14 (57.1%) patients were adjudicated by the RAC as responders to NOE-105 treatment, with scores of “Very Much Improved” reported in 2/14 (14.3%) patients, “Much Improved” reported in 4/14 (28.6%) patients, and “Minimally Improved” reported in 2/14 (14.3%) patients.
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End point type |
Primary
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End point timeframe |
Day 85
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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: The statistical methods focused primarily on descriptive statistics showing the changes over time in the efficacy endpoints. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Supplementary Measure to Primary Endpoint: “Response” as assessed by the Investigator using the TS-CGI-C scale [2] | ||||||||||
End point description |
Investigators’ assessment of “Response” using the TS-CGI-C scale (supplementary measure) with 8 responders (8/13, 61.5%).
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End point type |
Primary
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End point timeframe |
D85
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| Notes [2] - 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: The statistical methods focused primarily on descriptive statistics showing the changes over time in the efficacy endpoints. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Incidence and severity of AEs. Laboratory and cardiovascular safety were also evaluated | ||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 28 days after last dose
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change from Baseline to Week 12/EoT in the YGTSS as measured by the TTS | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From baseline to Day 85/EOT
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| No statistical analyses for this end point | |||||||||||
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End point title |
Investigator-assessed TS-CGI-S scale from Baseline to Week 12/EoT | ||||||||
End point description |
Investigator-assessed clinical global impression of change: the LS mean (95% CI) changes (reductions) from baseline in the Investigator-assessed TS-CGI-S scores
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End point type |
Secondary
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End point timeframe |
Day 85/EOT
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| No statistical analyses for this end point | |||||||||
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End point title |
Change from Baseline to Week 12/EoT[2] in the YGTSS (completers only) | ||||||||
End point description |
A post-hoc analysis was performed of change from baseline to Day 85 (i.e., Week 12) in YGTSS TTS, including all patients who completed the full 12-week treatment period and attended the Day 85 study visit and reached a final dose between 10 and 15 mg.
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End point type |
Secondary
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End point timeframe |
From baseline to Day 85/EOT
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| No statistical analyses for this end point | |||||||||
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End point title |
PGI-C as completed by patients from Baseline to Week 12/EoT | ||||||||||||||||||||||
End point description |
Patients used an anchored-based assessment, in which, at the baseline visit, the patients were provided with a script and were requested to perform a voice recording. At W12/EoT, the patient was requested to listen to their baseline voice recording, and then rate the PGI-C comparing versus the baseline anchored with the voice recording
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End point type |
Secondary
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End point timeframe |
Baseline to Day 85/EoT
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Patient reported rating of the MSQ from Baseline to Week 12/EoT | ||||||||||||||||||||||
End point description |
The 7-point MSQ (from “extremely dissatisfied” to “extremely satisfied”) was completed by the patient at the Day 85 visit.
The number and percentage of patients in each MSQ response category were presented, where the percentages were calculated from the number of patients completing the required 12 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline to Day 85/EoT
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Addendum to Primary Endpoint: Response to Study Treatment in Completers With A Final Dosing of NOE-105 Between 10 And 15 mg/Day | ||||||||||
End point description |
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End point type |
Post-hoc
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End point timeframe |
Day 85
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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 |
Day 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 28 days after last dose
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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 |
24.0
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Reporting groups
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Reporting group title |
NOE-105 Treatment
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Reporting group description |
Single arm of the study, dose escalation from 2.5 mg once daily to a maximum of 15 mg once daily (increased in 2.5 mg increments every week at discretion of the investigator). If intolerance occurred at any given dose, the daily dose of NOE-105 could be reduced by 2.5 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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10 Dec 2020 |
To provide clarification on the study procedures:
- Baseline laboratory safety assessments
- Study treatment compliance
- PGI-C completion by patients |
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22 Sep 2021 |
•To reduce the starting dose of NOE-105 from 5 mg to 2.5 mg to further improve tolerability, and specify that the IMP should be taken with the evening meal, since food has been shown to reduce Cmax, in order to improve tolerability
• To provide clarity on inclusion and exclusion criteria
• To ensure that previous treatments for TS are captured |
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06 Dec 2021 |
• To update the benefit/risk section of the Study Protocol and to add mitigation measures in case of study disruption due to public health crisis
• To provide details on measures that would be put into place at times of study disruption during a civil crisis, natural disaster, or public health crisis (eg, from quarantines and resulting sites closures, regional travel restrictions, considerations if study site personnel or trial patients become infected with SARS-CoV-2) which would prevent patients from visiting study sites. |
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21 Sep 2022 |
• To allow the recruitment of up to 5 adolescent patients with TS and to increase the number of patients from 10 to 18.
• To exclude patients with positive urine drug screen for cannabinoids, cocaine, or nonprescribed opiates at screening.
• To add PK assessments to inform the modelling of the PK of NOE-105 in adolescent patients |
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03 Feb 2023 |
• To implement additional safety measures to monitor NOE-105 tolerability, as this was the first time that NOE-105 was to be administered to subjects < 18 years of age:
- A staggered recruitment was implemented as a prudent approach
- It was added that patients had to remain in the clinic for 2 hours following the first dose of study treatment for safety monitoring
- Newly included a DSMB
- Provided adjusted instructions on the Investigator support to the patient in case of SIB emergence in adolescents
• To update the table of risks |
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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. | |||
| None reported | |||
