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

Rett Syndrome Clinical Trial

— STARS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02790034
• Other study ID #: Sarizotan/001/II/2015
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: October 26, 2016
• Est. completion date: May 4, 2020

Study information

• Verified date: November 2021
• Source: Newron Pharmaceuticals SPA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the safety, tolerability and efficacy of Sarizotan in reducing respiratory abnormalities in Rett Syndrome in an initial double blind 24 week period followed by an open label treatment phase of up to 168 weeks (the latter for patients with no safety and tolerability issues).

Description:

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 129
• Est. completion date: May 4, 2020
• Est. primary completion date: August 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Rett Syndrome
• Signs and Symptoms, Respiratory
• Syndrome

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Australia	South Metropolitan Health Service Fiona Stanley Hospital	Murdoch	Western Australia
India	Vijaya Health Centre	Chennai	Tamilnadu
India	Amrita Institute of Medical Sciences	Kochi	Kerala
India	Jaslok Hospital and Research centre	Mumbai
India	P.D. Hinduja National Hospital and Medical Research Centre	Mumbai
India	All India Institute of Medical Sciences	New Delhi
Italy	U.O. Neuropsichiatria Infantile	Milano
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena	Tuscany
United Kingdom	King's College Hospital	London
United States	University of Alabama	Birmingham	Alabama
United States	Rush University Medical Center	Chicago	Illinois
United States	Baylor College of Medicine	Houston	Texas
United States	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota
United States	University of California	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Newron Pharmaceuticals SPA

Countries where clinical trial is conducted

United States,  Australia,  India,  Italy,  United Kingdom, 

References & Publications (29)

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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. — View Citation

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in Respiratory Abnormality in Patients With Rett Syndrome	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.	Baseline up to week 24
Secondary	Efficacy of Sarizotan Assessed by the Caregiver-rated Impression of Change	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)	24 weeks