Trial Outcomes & Findings for Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms (NCT NCT02790034)

Last Updated: 2021-12-21

Results Overview

Measured as the percent change in the number of apnea episodes per hour during awake time, calculated using an ambulatory data acquisition system (BioRadioTM) as part of home monitoring procedure. BioRadioTM record specific respiratory and cardiac parameters.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

129 participants

Primary outcome timeframe

Baseline up to week 24

Results posted on

2021-12-21

Participant Flow

The study was conducted at 14 sites in 5 countries. Enrollment occurred from 26-Oct-2016 through February 2019 . An analysis was planned when the primary efficacy data at Week 24 were available for all patients (06 August 2019 - last patient last visit for double-blind part of the study). Patients without safety and tolerability issues continued in the open label with sarizotan for an additional 24 weeks and then another 48 weeks if no safety issues were present.

A total of 198 patients were screened, of which 69 (34.8%) patients were screen failures. A total of 129 patients were randomized in the study. A total of 128 patients were exposed to at least one dose of IMP, with placebo ITT group (40) vs safety pop (39).

Participant milestones

Participant milestones
Measure	Sarizotan Low Dose 2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	Sarizotan High Dose 5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo Placebo bid for 24 wks DB
Overall Study STARTED	33	56	40
Overall Study COMPLETED	27	46	36
Overall Study NOT COMPLETED	6	10	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sarizotan Low Dose n=33 Participants 2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	Sarizotan High Dose n=56 Participants 5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo n=40 Participants Placebo BID	Total n=129 Participants Total of all reporting groups
Age, Categorical <=18 years	23 Participants n=5 Participants	35 Participants n=7 Participants	27 Participants n=5 Participants	85 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	21 Participants n=7 Participants	13 Participants n=5 Participants	44 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	13.23 years STANDARD_DEVIATION 7.195 • n=5 Participants	15.55 years STANDARD_DEVIATION 9.362 • n=7 Participants	14.13 years STANDARD_DEVIATION 9.155 • n=5 Participants	14.51 years STANDARD_DEVIATION 8.780 • n=4 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	56 Participants n=7 Participants	40 Participants n=5 Participants	129 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	51 Participants n=7 Participants	36 Participants n=5 Participants	116 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	16 Participants n=7 Participants	13 Participants n=5 Participants	37 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	37 Participants n=7 Participants	22 Participants n=5 Participants	82 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment United States	11 Participants n=5 Participants	19 Participants n=7 Participants	11 Participants n=5 Participants	41 Participants n=4 Participants
Region of Enrollment Italy	8 Participants n=5 Participants	13 Participants n=7 Participants	9 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment United Kingdom	5 Participants n=5 Participants	10 Participants n=7 Participants	6 Participants n=5 Participants	21 Participants n=4 Participants
Region of Enrollment Australia	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Region of Enrollment India	8 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	34 Participants n=4 Participants
Duration of Rett syndrome	87.90 months STANDARD_DEVIATION 72.536 • n=5 Participants	97.18 months STANDARD_DEVIATION 72.922 • n=7 Participants	73.94 months STANDARD_DEVIATION 65.800 • n=5 Participants	87.94 months STANDARD_DEVIATION 70.696 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to week 24

Population: The ITT population included all patients who were randomized to treatment. This population was used for all efficacy analysis.

Outcome measures

Outcome measures
Measure	Sarizotan Low Dose n=33 Participants 2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	Sarizotan High Dose n=56 Participants 5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo n=40 Participants Placebo BID
Reduction in Respiratory Abnormality in Patients With Rett Syndrome	1.54 % of change in mean counts per hr Standard Error 10.1228	13.211 % of change in mean counts per hr Standard Error 7.5075	18.503 % of change in mean counts per hr Standard Error 8.441

SECONDARY outcome

Timeframe: 24 weeks

Population: The ITT population included all patients who were randomized to treatment. This population was used for all efficacy analysis.

Caregiver-rated Impression of Change (CIC): 7-point scale requiring the caregiver to rate how much the patient's illness has improved or worsened relative to the baseline state. 7-point Likert-type scale for which ratings range from 1 = very much improved to 7 = very much worse, with 4 = no change. This caregiver-rated measure considered activities, behavior, mood and functioning. This rating was performed in consultation with the study Investigator but was based largely on the caregivers' evaluation during the reporting period. The single rating of the CIC was to be based on changes in the following domains: • Activities (watching TV, interest in conversations around her, cooperation during toileting, dressing/bathing, etc.), • Communication (verbal or by eye movements, hand movements, or head movements), • Behavior (agitation, refusal to feed, scratching, social avoidance), • Participation in family/outdoor/social events)

Outcome measures

Outcome measures
Measure	Sarizotan Low Dose n=33 Participants 2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg)	Sarizotan High Dose n=56 Participants 5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg)	Placebo n=40 Participants Placebo BID
Efficacy of Sarizotan Assessed by the Caregiver-rated Impression of Change	3.6 score on a scale Standard Deviation 0.67	3.5 score on a scale Standard Deviation 1.12	3.4 score on a scale Standard Deviation 0.79

Adverse Events

Sarizotan Low Dose

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

Sarizotan High Dose

Serious events: 10 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sarizotan Low Dose n=33 participants at risk 2 mg or 5 mg bid based on age and weight criteria for 24 wks DB 2 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 5 mg bid (≥13 years of age and weighing ≥25 kg) Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.	Sarizotan High Dose n=56 participants at risk 5 mg or 10 mg bid based on age and weight criteria for 24 wks DB 5 mg bid (4 to \<13 years; ≥13 years of age and weighing \<25 kg 10 mg bid (≥13 years of age and weighing ≥25 kg) Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.	Placebo n=39 participants at risk Placebo bid respectively Placebo: placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
Respiratory, thoracic and mediastinal disorders Cough	3.0% 1/33 • Number of events 1 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	5.4% 3/56 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	10.3% 4/39 • Number of events 4 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Nervous system disorders Seizure	24.2% 8/33 • Number of events 8 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	26.8% 15/56 • Number of events 15 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	12.8% 5/39 • Number of events 5 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Nervous system disorders Somnolence	6.1% 2/33 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	17.9% 10/56 • Number of events 10 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	15.4% 6/39 • Number of events 6 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Nervous system disorders Psychomotor hyperactivity	12.1% 4/33 • Number of events 4 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	1.8% 1/56 • Number of events 1 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	7.7% 3/39 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Nervous system disorders Dystonia	9.1% 3/33 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	5.4% 3/56 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	2.6% 1/39 • Number of events 1 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
General disorders Pyrexia	12.1% 4/33 • Number of events 4 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	5.4% 3/56 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	0.00% 0/39 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Psychiatric disorders Sleep Disorder	9.1% 3/33 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	7.1% 4/56 • Number of events 4 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	2.6% 1/39 • Number of events 1 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Psychiatric disorders Insomnia	9.1% 3/33 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	3.6% 2/56 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	5.1% 2/39 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Gastrointestinal disorders Diarrhoea	6.1% 2/33 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	7.1% 4/56 • Number of events 4 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	10.3% 4/39 • Number of events 4 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Gastrointestinal disorders Constipation	6.1% 2/33 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	8.9% 5/56 • Number of events 5 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	5.1% 2/39 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Gastrointestinal disorders Vomiting	15.2% 5/33 • Number of events 5 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	3.6% 2/56 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	5.1% 2/39 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Infections and infestations Urinary Tract Infection	6.1% 2/33 • Number of events 2 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	5.4% 3/56 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	7.7% 3/39 • Number of events 3 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP
Infections and infestations Upper respiratory tract infection	3.0% 1/33 • Number of events 1 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	8.9% 5/56 • Number of events 5 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP	2.6% 1/39 • Number of events 1 • AEs will be collected, from the time of signing of Informed Consent to the end of the safety follow-up period (14 days after last dose of study medication at 24 weeks). In addition, all subjects will be followed up for 30 days after last dose for SAEs, up to a total of 28 weeks. Analysis population = safety population defined as all patients randomized and exposed to at least one dose of IMP. One patient randomized to placebo treatment did not receive IMP, hence placebo ITT group (40) vs safety pop (39). Classification of the Event: Classify the event as either serious or non-serious Description of Signs or Symptoms: Whenever possible, record a specific diagnosis for the event Start/stop date Intensity (mild, moderate, severe) Causality Action taken with IMP

Additional Information

Ravi Anand MD, Chief Medical Officer

Newron Pharmaceuticals S.p.A.

Phone: +41 793741364

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER