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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 : Active, not recruiting
First Posted : June 3, 2016
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
Newron Pharmaceuticals SPA

Brief Summary:
This study evaluates the safety, tolerability and efficacy of Sarizotan in reducing respiratory abnormalities in Rett Syndrome.

Condition or disease Intervention/treatment Phase
Rett Syndrome Drug: Sarizotan Drug: Placebo Phase 2 Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 129 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : August 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rett Syndrome

Arm Intervention/treatment
Active Comparator: Sarizotan
Between 2 to 10 mg bid based on age and weight criteria.
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

Placebo Comparator: Placebo
Placebo bid respectively
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.


  9. 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.

  10. 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.

  11. 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.

  12. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02790034


Locations
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United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35233
United States, California
University of California
San Diego, California, United States, 92093
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Minnesota
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, United States, 55101
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Australia, Western Australia
South Metropolitan Health Service Fiona Stanley Hospital
Murdoch, Western Australia, Australia, 6961
India
Amrita Institute of Medical Sciences
Kochi, Kerala, India, 682041
Vijaya Health Centre
Chennai, Tamilnadu, India, 600 026
Apollo Gleneagles Hospitals
Kolkata, West Bengal, India, 700054
P.D. Hinduja National Hospital and Medical Research Centre
Mumbai, India, 400 016
Jaslok Hospital and Research centre
Mumbai, India, 400 026
All India Institute of Medical Sciences
New Delhi, India, 110 029
Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, Tuscany, Italy, 53100
U.O. Neuropsichiatria Infantile
Milano, Italy, 20142
United Kingdom
King's College Hospital
London, United Kingdom, SE5 8AF
Sponsors and Collaborators
Newron Pharmaceuticals SPA
Investigators
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Study Director: Ravi Anand, MD Newron Pharmaceuticals

Publications:
Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, May 28, 2009 (v4.03 June 14, 2010), U.S. Department of Health and Human Services.
Guy W (Ed). Clinical Global Impressions. In ECDEU Assessment Manual for Psychopharmacology, revised, U.S. Department of Health, Education and Welfare Pub. No. (ADM) 76-338. Rockville, MD: NIMH, 1976, 217-222.
Landon C. Respiratory monitoring: Advantages of inductive plethysmography over impedance pneumograpy. VivoMetrics, VMLA-039-02, 2003.

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Responsible Party: Newron Pharmaceuticals SPA
ClinicalTrials.gov Identifier: NCT02790034     History of Changes
Other Study ID Numbers: Sarizotan/001/II/2015
First Posted: June 3, 2016    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: February 2019
Additional relevant MeSH terms:
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Rett Syndrome
Syndrome
Signs and Symptoms, Respiratory
Disease
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Signs and Symptoms