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

Newron Pharmaceuticals

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Rett Syndrome

Treatments: Drug: Sarizotan high dose; Drug: Placebo; Drug: Sarizotan low dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT02790034

Sarizotan/001/II/2015

Details and patient eligibility

About

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).

Full 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.

Enrollment: 129 patients

Sex: All

Ages: 4+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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129 participants in 3 patient groups, including a placebo group

Sarizotan low dose

Experimental group

Description:

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)

Treatment:

Drug: Sarizotan low dose

Sarizotan high dose

Experimental group

Description:

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)

Treatment:

Drug: Sarizotan high dose

Placebo

Placebo Comparator group

Description:

Placebo bid for 24 wks DB age 4 and above

Treatment:

Drug: Placebo