Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD)
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Prospective Safety, Tolerance, Pharmacodynamics and Pharmacokinetics Study of Sobetirome in Male Subjects Diagnosed With X-linked Adrenoleukodystrophy (X-ALD)|
- Change from Baseline in very long chain fatty acid (VLCFA) levels [ Time Frame: Day 14 and Day 28 of sobetirome dosing ] [ Designated as safety issue: No ]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.
- Evidence of changes in thyroid function from baseline confirmed by measured changes in TSH and/or free T4 [ Time Frame: Day 14 and 28 of sobetirome dosing ] [ Designated as safety issue: Yes ]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.
- Number of participants with adverse events from baseline [ Time Frame: Every 7 days to outcome visit day and again at end of study visit day ] [ Designated as safety issue: Yes ]Adverse events will be assessed by physical examination and ECG
- Peak Plasma Concentration (Cmax) of Sobetirome [ Time Frame: Day 1 ] [ Designated as safety issue: No ]A pharmacokinetic analysis to assess sobetirome exposure in X-ALD subjects.
|Study Start Date:||April 2013|
|Study Completion Date:||February 2014|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
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.
50 mcg or 100 mcg once-daily oral
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01787578
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||David Koeller, MD||Oregon Health and Science University|