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

This study has been withdrawn prior to enrollment.
(revisions to original study protocol underway)
Sponsor:
Information provided by (Responsible Party):
Thomas S. Scanlan, Oregon Health & Science University
ClinicalTrials.gov Identifier:
NCT01787578
First received: February 6, 2013
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
X-Linked Adrenoleukodystrophy
Adrenomyeloneuropathy
Drug: Sobetirome
Phase 1

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 0
Study Start Date: April 2013
Study Completion Date: February 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01787578

Locations
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Thomas S. Scanlan
Investigators
Principal Investigator: David Koeller, MD Oregon Health and Science University
  More Information

No publications provided

Responsible Party: Thomas S. Scanlan, Professor of Physiology & Pharmacology, Oregon Health & Science University
ClinicalTrials.gov Identifier: NCT01787578     History of Changes
Other Study ID Numbers: Sobetirome-CLIN-006, CTSA grant (UL1TR000128)
Study First Received: February 6, 2013
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Oregon Health and Science University:
X-linked adrenoleukodystrophy
adrenomyeloneuropathy
sobetirome
thyroid
thyromimetic

Additional relevant MeSH terms:
Adrenoleukodystrophy
Adrenal Gland Diseases
Adrenal Insufficiency
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Endocrine System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hereditary Central Nervous System Demyelinating Diseases
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Leukoencephalopathies
Mental Retardation, X-Linked
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Peroxisomal Disorders

ClinicalTrials.gov processed this record on October 30, 2014