A 6 Month Study to Evaluate the Efficacy, Safety and Tolerability of drug â??Sarizotanâ?? in Patients with Rett Syndrome having difficulty in breathing. This is a Randomized, Double-Blind (the doctor and the patient not knowing the treatment), Placebo (inactive substance) -Controlled study.
- Conditions
- Health Condition 1: null- Rett Syndrome with Respiratory Symptoms
- Registration Number
- CTRI/2017/01/007738
- Lead Sponsor
- ewron Pharmaceuticals SpA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Demographics
1.Female or male >= 13 years of age.
2.Body weight >= 25 kg.
Diagnostic
3.Diagnosis of Rett syndrome based on consensus clinical criteria (Neul et al, 2010; Appendix 4). A test for MECP2 mutations (Xq28) will be performed at screening if results from an accredited laboratory are not available; selection for the trial is not contingent on the results of the MECP2 test. Patients with MECP2 duplications will not be eligible.
4.One or more of the following breathing dysfunctions: periodic apnea during wakefulness; intermittent hyperventilation; breath holding spells; air swallowing; forced expulsion of air or saliva.
5.Patient meets all of the following criteria related to breathing abnormalities:
a.Parent report of 10 episodes or more of breathing abnormality per day during wakefulness in the week prior to the screening visit;
b.Time per hour spent on normal breathing is less than 90% of the total time per hour of wakefulness (i.e., >=10% of the time should be abnormal breathing);
c.Has at least 10 episodes of breathing dysrhythmia, defined by episodes >=10 seconds of breath holding (apnea), per hour during cardiorespiratory monitoring (performed with home/ambulatory monitoring system during screening period).
6. Stable medication regimen for 4 weeks prior to beginning the study (if receiving services - physical, occupational, or speech therapy - subjects must be on a stable regimen of these services for 3 months prior to beginning the study). Female patients of childbearing potential are to use adequate contraception as recommended by their Health Care Provider.
Procedural
7.Parent/legal guardian/representative has provided written consent prior to the patient participating in the study. Where feasible, consent or assent for patients less than 18 years of age, has also been provided by the patient.
8.Ability to swallow study medication provided either as capsules or combined with food/drink.
9.Patient is cooperative, willing to complete all aspects of the study, and capable of doing so with assistance of a caregiver.
10.Caregiver is able to understand the instructions and fully participate.
1.Meets any of the diagnostic exclusion criteria for Rett syndrome, Typical (Neul et al, 2010; Appendix 4);
2.Patient is participating in a clinical trial with another investigational drug or has taken an investigational drug within one month or 5 half-lives (whichever is longer) prior to screening;
3.Hypersensitivity to sarizotan or other 5-HT1a agonists;
4.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 patientâ??s Rett syndrome;
5.QTcF interval on the ECG is greater than 450 msec.
6.Surgery planned during the study (except for insertion of gastrostomy tube);
7.Severe diabetes mellitus or fatty acid oxidation disorder.
8. 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.
9.Females who are pregnant, breastfeeding, or of childbearing potential and not using adequate contraception, as recommended by their Health Care Provider.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary Efficacy Objective: <br/ ><br>â?¢To evaluate the effect of sarizotan (5 to 10 mg bid), compared to placebo, on reducing the number of apnea episodes, during awake time, in patients with RTT with respiratory abnormalities. <br/ ><br>Key Secondary Efficacy Objective: <br/ ><br>â?¢To evaluate the effect of sarizotan (5 to 10 mg bid), compared to placebo, on the Caregiver-rated Impression of Change (CIC) from baseline;Timepoint: 6 months
- Secondary Outcome Measures
Name Time Method Safety and tolerability of sarizotan 5-10mg bid in RTT with resp abnormalities <br/ ><br>Efficacy of sarizotan Vs placebo on: <br/ ><br>-Other RTT respiratory symptoms during awake time including: <br/ ><br>-time spent with breathing dysrhythmia <br/ ><br>-hyperventilation episodes <br/ ><br>-O2 saturation <br/ ><br>-Respiratory Distress Index:episodes for breath-holding and hyperventilation,drops in O2 to 90 <br/ ><br>-breathing dysrhythmia episodes <br/ ><br>-Motor behavior <br/ ><br>-Global change <br/ ><br>-Caregiver burden <br/ ><br>-Assessing RTT symptoms <br/ ><br>-PK profile Vs adultsTimepoint: 6 months