Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms
NCT ID: NCT02790034
Last Updated: 2021-12-21
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2/PHASE3
129 participants
INTERVENTIONAL
2016-10-26
2020-05-04
Brief Summary
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Detailed Description
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All patients who have completed the final evaluations at Week 24 (Day 168) and have no safety or tolerability issues that would preclude continuing on the study medication and have been compliant with the trial requirements will have the option of continuing open-label treatment with Sarizotan for up to 168 weeks.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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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 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). Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
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)
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) Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients
Placebo
Placebo bid for 24 wks DB age 4 and above
Placebo
Placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
Interventions
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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). Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
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) Assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients
Placebo
Placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
4 Years
ALL
No
Sponsors
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Newron Pharmaceuticals SPA
INDUSTRY
Responsible Party
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Principal Investigators
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Ravi Anand, MD
Role: STUDY_DIRECTOR
Newron Pharmaceuticals
Locations
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University of Alabama
Birmingham, Alabama, United States
University of California
San Diego, California, United States
Rush University Medical Center
Chicago, Illinois, United States
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, United States
Baylor College of Medicine
Houston, Texas, United States
South Metropolitan Health Service Fiona Stanley Hospital
Murdoch, Western Australia, Australia
Amrita Institute of Medical Sciences
Kochi, Kerala, India
Vijaya Health Centre
Chennai, Tamil Nadu, India
P.D. Hinduja National Hospital and Medical Research Centre
Mumbai, , India
Jaslok Hospital and Research centre
Mumbai, , India
All India Institute of Medical Sciences
New Delhi, , India
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, Tuscany, Italy
U.O. Neuropsichiatria Infantile
Milan, , Italy
King's College Hospital
London, , United Kingdom
Countries
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References
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Abdala AP, Lioy DT, Garg SK, Knopp SJ, Paton JF, Bissonnette JM. Effect of Sarizotan, a 5-HT1a and D2-like receptor agonist, on respiration in three mouse models of Rett syndrome. Am J Respir Cell Mol Biol. 2014 Jun;50(6):1031-9. doi: 10.1165/rcmb.2013-0372OC.
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Abdala AP, Dutschmann M, Bissonnette JM, Paton JF. Correction of respiratory disorders in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18208-13. doi: 10.1073/pnas.1012104107. Epub 2010 Oct 4.
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Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, Zoghbi H, Percy A, Glaze DG. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008 Apr 15;70(16):1313-21. doi: 10.1212/01.wnl.0000291011.54508.aa. Epub 2008 Mar 12.
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Gualniera L, Singh J, Fiori F, Santosh P. Emotional Behavioural and Autonomic Dysregulation (EBAD) in Rett Syndrome - EDA and HRV monitoring using wearable sensor technology. J Psychiatr Res. 2021 Jun;138:186-193. doi: 10.1016/j.jpsychires.2021.03.052. Epub 2021 Apr 7.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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Sarizotan/001/II/2015
Identifier Type: -
Identifier Source: org_study_id