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

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ClinicalTrials.gov Identifier: NCT02790034
Recruitment Status : Recruiting
First Posted : June 3, 2016
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Newron Pharmaceuticals SPA

May 24, 2016
June 3, 2016
September 11, 2018
August 2016
April 2019   (Final data collection date for primary outcome measure)
Reduction in respiratory abnormality in patients with Rett syndrome [ Time Frame: 3 days prior to Baseline up to week 24 ]
Measured as the percent reduction 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.
  • Reduction in respiratory abnormality in patients with Rett syndrome [ Time Frame: 3 days prior to Baseline up to week 24 ]
    Measured as the percent reduction 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.
  • Efficacy of sarizotan assessed by the caregiver [ Time Frame: 24 weeks ]
    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.
Complete list of historical versions of study NCT02790034 on ClinicalTrials.gov Archive Site
  • Efficacy of sarizotan assessed by the caregiver [ Time Frame: 24 weeks ]
    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.
  • Safety and tolerability of sarizotan in patients with Rett syndrome with respiratory symptoms. [ Time Frame: 24 weeks ]
    Adverse events (AEs),Vital signs (systolic/diastolic blood pressure, pulse, body weight, body temperature, respiratory rate),Laboratory evaluations (blood chemistry, hematology, urinalysis, plasma ACTH, cortisol and prolactin),Electrocardiogram (ECG) - 12-lead standard,Physical examination Neurological examination, Ophthalmology examination (including OCT if feasible), Tanner staging
  • Respiratory symptoms - Percent time spent with breathing dysrhythmia per hour [ Time Frame: 24 weeks ]
    Percent time spent with breathing dysrhythmia per hour. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Number of hyperventilation episodes [ Time Frame: 24 weeks ]
    Number of hyperventilation episodes. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Oxygen saturation [ Time Frame: 24 weeks ]
    Oxygen saturation. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Respiratory Distress Index; [ Time Frame: 24 weeks ]
    Respiratory Distress Index; These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Incidence of breathing dysrhythmia episodes [ Time Frame: 24 weeks ]
    Incidence of breathing dysrhythmia episodes. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Motor behaviour [ Time Frame: 24 weeks ]

    Assessed by Motor-Behavioral Assessment Scale:

    I. Behavioral/Social Assessment - 16 items II. Orofacial/Respiratory Assessment - 7 items III. Motor Assessment/Physical Signs - 14 items.

  • Global change from baseline [ Time Frame: 24 weeks ]
    assessed by the Clinical Global Impression of Change (CGI-C): 7-point scale requiring the clinician to rate how much the patient's illness has improved or worsened relative to the baseline state.
  • Caregiver burden [ Time Frame: 24 weeks ]
    Caregiver Top 3 Concerns: Visual Analogue Scale-based evaluation of three priority concerns identified by caregivers related to the patient's RTT syndrome which they would like to see change as a result of treatment. The severity of these concerns is rated by the caregiver at baseline and is evaluated again at subsequent follow-up visits.
  • Overall assessment of symptoms of Rett syndrome [ Time Frame: 24 weeks ]
    Assessed by Rett Syndrome Clinical Severity Scale (RCSS): Frequency and manageability of seizures, respiratory irregularities, scoliosis, ability to walk (gait apraxia), hand use, speech and sleep; yielding total and feature-specific scores.
  • Pharmacokinetics profile of sarizotan and its comparison with the profile in adults [ Time Frame: Baseline, 1 and 4 hr post-dose on Day 1, and 1 and 4 hr post-dose on Day 15 ]
    measurement of plasma levels of Sarizotan and its major metabolites from blood samples collected from the patients at the specified time points.
  • Safety and tolerability of sarizotan in patients with Rett syndrome with respiratory symptoms. [ Time Frame: 24 weeks ]
    Adverse events (AEs),Vital signs (systolic/diastolic blood pressure, pulse, body weight, body temperature, respiratory rate),Laboratory evaluations (blood chemistry, hematology, urinalysis, plasma ACTH, cortisol and prolactin),Electrocardiogram (ECG) - 12-lead standard,Physical examination Neurological examination, Ophthalmology examination (including OCT if feasible), Tanner staging
  • Respiratory symptoms - Percent time spent with breathing dysrhythmia per hour [ Time Frame: 24 weeks ]
    Percent time spent with breathing dysrhythmia per hour. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Number of hyperventilation episodes [ Time Frame: 24 weeks ]
    Number of hyperventilation episodes. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Oxygen saturation [ Time Frame: 24 weeks ]
    Oxygen saturation. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Respiratory Distress Index; [ Time Frame: 24 weeks ]
    Respiratory Distress Index; These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Respiratory symptoms - Incidence of breathing dysrhythmia episodes [ Time Frame: 24 weeks ]
    Incidence of breathing dysrhythmia episodes. These respiratory outcomes will be determined by assessment of changes in intra-subject values and group mean change values.
  • Motor behaviour [ Time Frame: 24 weeks ]

    Assessed by Motor-Behavioral Assessment Scale:

    I. Behavioral/Social Assessment - 16 items II. Orofacial/Respiratory Assessment - 7 items III. Motor Assessment/Physical Signs - 14 items.

  • Global change from baseline [ Time Frame: 24 weeks ]
    assessed by the Clinical Global Impression of Change (CGI-C): 7-point scale requiring the clinician to rate how much the patient's illness has improved or worsened relative to the baseline state.
  • Caregiver burden [ Time Frame: 24 weeks ]
    Caregiver Top 3 Concerns: Visual Analogue Scale-based evaluation of three priority concerns identified by caregivers related to the patient's RTT syndrome which they would like to see change as a result of treatment. The severity of these concerns is rated by the caregiver at baseline and is evaluated again at subsequent follow-up visits.
  • Overall assessment of symptoms of Rett syndrome [ Time Frame: 24 weeks ]
    Assessed by Rett Syndrome Clinical Severity Scale (RCSS): Frequency and manageability of seizures, respiratory irregularities, scoliosis, ability to walk (gait apraxia), hand use, speech and sleep; yielding total and feature-specific scores.
  • Pharmacokinetics profile of sarizotan and its comparison with the profile in adults [ Time Frame: Baseline, 1 and 4 hr post-dose on Day 1, and 1 and 4 hr post-dose on Day 15 ]
    measurement of plasma levels of Sarizotan and its major metabolites from blood samples collected from the patients at the specified time points.
Not Provided
Not Provided
 
Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms
A Randomised, Double-Blind, Placebo-Controlled 6-month Study to Evaluate the Efficacy, Safety, and Tolerability of Sarizotan in Patients With Rett Syndrome With Respiratory Symptoms
This study evaluates the safety, tolerability and efficacy of Sarizotan in reducing respiratory abnormalities in Rett Syndrome.
This is a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and efficacy of multiple doses of sarizotan in patients with Rett syndrome with respiratory abnormalities. The study participants will be randomized to either sarizotan between 2 and 10 mg bid or placebo bid, based on age and weight criteria.
Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Rett Syndrome
  • Drug: Sarizotan
    2 to 10 mg per day of Sarizotan followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
    Other Name: sarizotan hydrochloride
  • Drug: Placebo
    placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
    Other Name: Placebo capsules with microcrystalline cellulose
  • Active Comparator: Sarizotan
    Between 2 to 10 mg bid based on age and weight criteria.
    Intervention: Drug: Sarizotan
  • Placebo Comparator: Placebo
    Placebo bid respectively
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
129
Same as current
April 2019
April 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Body weight ≥ 10 kg
  • Age ≥ 4 years
  • Diagnosis of Rett syndrome based on consensus clinical criteria and patients with MECP2 duplications will not be eligible.
  • Has at least 10 episodes of breathing dysrhythmia, defined by episodes ≥10 seconds of breath holding (apnea), per hour during cardiorespiratory monitoring
  • Ability to take study medication provided either as capsules or combined with food/drink.
  • Patient is cooperative, willing to complete all aspects of the study, and capable of doing so with assistance of a caregiver.

Exclusion Criteria:

  • Meets any of the diagnostic exclusion criteria for Rett syndrome, Typical (Neul et al, 2010);
  • Patient is participating in a clinical trial with another investigational drug
  • Hypersensitivity to sarizotan or other 5-HT1a agonists;
  • Current clinically significant (as determined by Investigator) cardiovascular, respiratory (e.g. severe asthma), gastrointestinal, renal, hepatic, hematologic or other medical disorders, in addition to those directly related to the patient's Rett syndrome;
  • QTcF interval on the ECG is greater than 450 msec.
  • Surgery planned during the study (except for insertion of gastrostomy tube);
  • Severe diabetes mellitus or fatty acid oxidation disorder.
  • Ophthalmologic history including any of the following conditions: albino patients, family history of hereditary retinal disease, retinitis pigmentosa, any active retinopathy or severe diabetic retinopathy.
  • Females who are pregnant, breastfeeding, or of childbearing potential and not using a hormonal contraceptive.
Sexes Eligible for Study: All
4 Years and older   (Child, Adult, Older Adult)
No
Contact: Ravi Anand, MD +39 026103461 ravi@anand.ch
Australia,   India,   Italy,   United Kingdom,   United States
 
 
NCT02790034
Sarizotan/001/II/2015
Yes
Not Provided
Not Provided
Newron Pharmaceuticals SPA
Newron Pharmaceuticals SPA
Not Provided
Study Director: Ravi Anand, MD Newron Pharmaceuticals
Newron Pharmaceuticals SPA
September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP