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

A Prospective Safety, Tolerance, Pharmacodynamics and Pharmacokinetics Study of Sobetirome in Male Subjects Diagnosed With 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 Overview

• Status: Withdrawn
• Conditions: Adrenomyeloneuropathy; X-Linked Adrenoleukodystrophy
• Intervention / Treatment: Drug: Sobetirome

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sobetirome; 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; 50 mcg or 100 mcg once-daily oral; Other Names: GC-1; QRX-431

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Thomas S. Scanlan
• Investigators: Principal Investigator: David Koeller, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: February 6, 2013
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Estimate): February 14, 2014
• Last Update Submitted That Met QC Criteria: February 12, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: thyroid; X-linked adrenoleukodystrophy; adrenomyeloneuropathy; sobetirome; thyromimetic
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Leukoencephalopathies; Adrenal Gland Diseases; Hereditary Central Nervous System Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Adrenoleukodystrophy
• Other Study ID Numbers: Sobetirome-CLIN-006; CTSA grant (UL1TR000128) (Other Grant/Funding Number: Oregon Clinical & Translational Research Institute)