Adrenomyeloneuropathy, X-Linked Adrenoleukodystrophy
Conditions
Keywords
X-linked adrenoleukodystrophy, adrenomyeloneuropathy, sobetirome, thyroid, thyromimetic
Brief summary
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
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.
Interventions
DRUGSobetirome
50 mcg or 100 mcg once-daily oral
Sponsors
Thomas S. Scanlan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in very long chain fatty acid (VLCFA) levels | Day 14 and Day 28 of sobetirome dosing | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evidence of changes in thyroid function from baseline confirmed by measured changes in TSH and/or free T4 | Day 14 and 28 of sobetirome dosing | 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 | Every 7 days to outcome visit day and again at end of study visit day | Adverse events will be assessed by physical examination and ECG |
| Peak Plasma Concentration (Cmax) of Sobetirome | Day 1 | A pharmacokinetic analysis to assess sobetirome exposure in X-ALD subjects. |
Countries
United States
Outcome results
None listed