Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerance, pharmacokinetics, and pharmacodynamics of sobetirome, a selective thyroid hormone analog, in adult male X-ALD patients.

Detailed Description
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Subjects will have a screening visit within 6 weeks prior to the Baseline visit. At Baseline visit blood will be drawn and to establish baseline values for plasma and red blood cell (RBC) very long chain fatty acids (VLCFA; C22, C24, and C26). Subjects will receive an oral dose of 50 mcg sobetirome once daily for 14 days beginning on Day 1. Subjects will be kept in the clinic on Day 1 for 16 hours following their initial dose of sobetirome for repeat blood sampling for pharmacokinetic analysis. Subjects will return to the clinic on days 7, 15, 21 and 28 for blood collection for VLCFA measurements. On day 15, after safety assessment, subjects will receive an increased dose of 100 mcg and this dose will be continued once daily through Day 28. Subjects will continue to return to the clinic weekly for blood and urine collection and safety assessments. Subjects will return to the clinic on day 42 for an End of Study visit that will involve a final measurement of VLCFA and blood and urine safety labs to check for reversibility. Safety labs will include serum chemistry, free fatty acid profile, hematology, urinalysis, and thyroid function. Subjects will be monitored with ECGs, vital signs, physical exams and assessment of adverse events.

Official Title
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A Prospective Safety, Tolerance, Pharmacodynamics and Pharmacokinetics Study of Sobetirome in Male Subjects Diagnosed With X-linked Adrenoleukodystrophy (X-ALD)

Conditions
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X-Linked Adrenoleukodystrophy, Adrenomyeloneuropathy

Intervention / Treatment
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* Drug: Sobetirome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males 18-65 years old X-ALD diagnosis by either elevated VLCFAs or DNA testing must sign informed consent and agree to complete required clinic visits. Exclusion Criteria: female gender abnormal laboratory test results (except VLCFA) at screening visit history of coronary artery disease use of triiodothyronine therapy abnormal thyroid function test at screening visit untreated adrenal insufficiency currently taking Lorenzo's Oil or other VLCFA lowering agent participation in investigational drug study within 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sobetirome<br>Subjects will receive oral doses of sobetirome. All subjects will start with a 50 mcg dose, once-daily for 14 days. If this dose proves safe and well tolerated, subjects will receive a 100 mcg dose once-daily for an additional 14 days. | Drug: Sobetirome<br>* 50 mcg or 100 mcg once-daily oral<br>* Other names: QRX-431;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in very long chain fatty acid (VLCFA) levels | Very long chain fatty acid (VLCFA) levels in plasma and erythrocytes will be measured after 14 days of 50 mcg sobetirome, and again after 14 days of 100 mcg sobetirome dosing. | Day 14 and Day 28 of sobetirome dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of changes in thyroid function from baseline confirmed by measured changes in TSH and/or free T4 | Thyroid function will be assessed my measurement of TSH and free T4 following 14 days of 50 mcg sobetirome, and again following 14 days of 100 mcg sobetirome dosing. | Day 14 and 28 of sobetirome dosing | 
| Number of participants with adverse events from baseline | Adverse events will be assessed by physical examination and ECG | Every 7 days to outcome visit day and again at end of study visit day | 
| Peak Plasma Concentration (Cmax) of Sobetirome | A pharmacokinetic analysis to assess sobetirome exposure in X-ALD subjects. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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X-linked adrenoleukodystrophy, adrenomyeloneuropathy, sobetirome, thyroid, thyromimetic