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

NCT02790034 | Terminated Phase 2 Results DMC

• 1 other identifier: Sarizotan/001/II/2015
• Study Type: interventional
• Target: 129
• Locations: 5 countries
• Sites: 14

Brief 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).

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Efficacy of Sarizotan Assessed by the Caregiver-rated Impression of Change

  24 weeks

Study Arms (3)

Sarizotan low dose

EXPERIMENTAL

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)

Drug: Sarizotan low dose

Sarizotan high dose

EXPERIMENTAL

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)

Drug: Sarizotan high dose

Placebo

PLACEBO COMPARATOR

Placebo bid for 24 wks DB age 4 and above

Drug: Placebo

Interventions

Sarizotan low dose DRUG

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 low dose

Sarizotan high dose DRUG

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

Sarizotan high dose

Placebo DRUG

Placebo BID followed by assessment of safety, tolerability and efficacy on reducing the respiratory symptoms in patients.

Placebo

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Newron Pharmaceuticals SPA: lead

Study Sites (14)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

University of California

San Diego, California, 92093, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

South Metropolitan Health Service Fiona Stanley Hospital

Murdoch, Western Australia, 6961, Australia

Location

Amrita Institute of Medical Sciences

Kochi, Kerala, 682041, India

Location

Vijaya Health Centre

Chennai, Tamil Nadu, 600 026, India

Location

P.D. Hinduja National Hospital and Medical Research Centre

Mumbai, 400 016, India

Location

Jaslok Hospital and Research centre

Mumbai, 400 026, India

Location

All India Institute of Medical Sciences

New Delhi, 110 029, India

Location

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, Tuscany, 53100, Italy

Location

U.O. Neuropsichiatria Infantile

Milan, 20142, Italy

Location

King's College Hospital

London, SE5 8AF, United Kingdom

Location

Related Publications (30)

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MeSH Terms

Conditions

Rett Syndrome

Interventions

sarizotan

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Limitations and Caveats

No efficacy evaluation was performed for the open label extension, as the study was terminated prematurely by the Sponsor based on lack of demonstrated efficacy in the double-blind period.

Results Point of Contact

• Title: Ravi Anand MD, Chief Medical Officer
• Organization: Newron Pharmaceuticals S.p.A.

regulatoryaffairs@newron.com

+41 793741364

Study Officials

• Ravi Anand, MD

  Newron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2016
• First Posted: June 3, 2016
• Study Start: October 26, 2016
• Primary Completion: August 6, 2019
• Study Completion: May 4, 2020
• Last Updated: December 21, 2021
• Results First Posted: December 21, 2021

Record last verified: 2021-11

Locations

IN (5); GB (1); IT (2); AU (1); US (5)