Clinical trial NCT01787578: Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD)
Official title: A Prospective Safety, Tolerance, Pharmacodynamics and Pharmacokinetics Study of Sobetirome in Male Subjects Diagnosed With X-linked Adrenoleukodystrophy (X-ALD)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: X-Linked Adrenoleukodystrophy
Adrenomyeloneuropathy
Keywords: X-linked adrenoleukodystrophy
adrenomyeloneuropathy
sobetirome
thyroid
thyromimetic
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2013-02-08
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in very long chain fatty acid (VLCFA) levels
timeFrame: Day 14 and Day 28 of sobetirome dosing
Secondary outcomes:
measure: Evidence of changes in thyroid function from baseline confirmed by measured changes in TSH and/or free T4
timeFrame: Day 14 and 28 of sobetirome dosing
measure: Number of participants with adverse events from baseline
timeFrame: Every 7 days to outcome visit day and again at end of study visit day
measure: Peak Plasma Concentration (Cmax) of Sobetirome
timeFrame: Day 1
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: David Koeller, MD
role: PRINCIPAL_INVESTIGATOR
References: