Pharmacokinetics of 9-cis-retinoic Acid (Alitretinoin, Toctino®) in Patients With Hepatic Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Frederik Grønhøj, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT01261923
First received: December 15, 2010
Last updated: January 26, 2013
Last verified: January 2013
  Purpose

This study aims to investigate whether liver patients may tolerate alitretinoin by comparing metabolism in 8 such patients with the metabolism in 8 healthy controls


Condition Intervention Phase
Hepatic Insufficiency
Drug: Alitretinoin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Pharmacokinetics of 9-cis-retinoic Acid (Alitretinoin, Toctino®) in Patients

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Primary Outcome Measures:
  • The investigators wish to investigate whether the metabolism of alitretinoin differs between healthy controls and patients with moderate to severe hepatic disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The metabolism of alitretinoin will be examined by measuring blood concentrations after time: 0 , ¼, ½, ¾, 1, 1¼, 1½, 2, 2½, 3, 3½, 4, 5, 6, 8, 10, 12 and 24 hours.


Enrollment: 16
Study Start Date: December 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alitretinoin - Hepatic Insufficiency
metabolism of 30 mg alitretinoin single dose in 8 patients with Hepatic Insufficiency
Drug: Alitretinoin
30 mg capsule of 9-cis-retinoic-acid (9-cis-RA)(Alitretinoin, Toctino®)
Other Name: 9-cis-retinoic-acid (9-cis-RA)(Alitretinoin, Toctino®)
Experimental: Alitretinoin - Hepatic Insufficiency Controls
metabolism of 30 mg alitretinoin single dose in 8 healthy controls.
Drug: Alitretinoin
30 mg capsule of 9-cis-retinoic-acid (9-cis-RA)(Alitretinoin, Toctino®)
Other Name: 9-cis-retinoic-acid (9-cis-RA)(Alitretinoin, Toctino®)

Detailed Description:

This study aims to investigate whether liver patients may tolerate alitretinoin.

Toctino (alitretinoin) is a vitamin A like substance that has proven effective in the treatment of specially hand eczema. The medicine is taken as capsules daily for up to 3 months. Toctino is currently only approved for patients with normal liver function, because it has never been studied how drug metabolism and excretion occurs in liver disease patients. This, however, the investigators want to examine in order to achieve an additional treatment for patients with severe hand eczema and concomitant liver disease.

The study is a collaboration between dermatology and medical department, Gentofte Hospital and University of Copenhagen, where blood and urine tests will be conducted. From the medical department, 8 patients diagnosed with liver disease will be recruited. Patients should only receive a single dose of Toctino (30 mg capsules). 20 blood samples and one urine sample will be taken over the next 24 hours (approximately 250-300 ml) to measure the concentration of Toctino in blood and urine. Moreover, the urine will be collected over 24 hours. Then the investigators will recruit an 8-person control group that is matched according to gender, age and weight. In this control group will take exactly the same samples. Based on determining concentrations in blood and urine will be able to mathematically calculate how Toctino is absorbed, distributed and excreted in liver disease patients in conjunction with a healthy control group. The study will therefore help to determine what dose of Toctino that would be preferable in liver disease patients.

The survey is estimated to be associated with a very low risk both for participating patients and control group. Toctino is an approved drug and side effects occur almost exclusively in long term treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Be medically stable for at least 1 month before the intake of 9-cis-RA.
  2. There must be an ultrasound scan of liver and abdomen within the last 3 months (liver size, ascites).
  3. In women of childbearing age, there must be a negative pregnancy test, while that to be used adequate contraception (the pill, coil or surgical sterilization) at least 1 month after taking the study medication.

Exclusion Criteria:

  1. Clinically significant deviations in routine blood tests (hematology, electrolytes and kid-ney, urinalysis). Differences attributable to underlying liver disease are excluded.
  2. Encephalopathy (> grade II)
  3. Concomitant treatment with drugs predominantly metabolised in the liver by CYP3A4.
  4. Clinically significant ECG changes, cardiovascular disease and AMI within the last 12 months
  5. Affected renal function judged by Cockcroft-Gault formula.
  6. Epilepsy or significant neurological disease that requires drug therapy.
  7. History of cerebrovascular relapse
  8. Esophagus bleeding
  9. Severe ascites
  10. HIV
  11. Mental illness.
  12. Active cancer
  13. Pregnancy or pregnancy plan within 3 months.
  14. Breastfeeding women.
  15. Participation in other clinical projects.
  16. Intake of clinical trial medication in the past month.
  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: NCT01261923

Locations
Denmark
Gentofte Hospital
Hellerup, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
Principal Investigator: Frederik Grønhøj, MD DMSci Gentofte Hospital
  More Information

No publications provided

Responsible Party: Frederik Grønhøj, MD, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT01261923     History of Changes
Other Study ID Numbers: Eudra CT 2010-020212-11
Study First Received: December 15, 2010
Last Updated: January 26, 2013
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: Ethics Committee

Additional relevant MeSH terms:
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Isotretinoin
Tretinoin
Alitretinoin
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Keratolytic Agents

ClinicalTrials.gov processed this record on August 21, 2014