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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01261923
Recruitment Status : Completed
First Posted : December 17, 2010
Last Update Posted : January 29, 2013
Information provided by (Responsible Party):
Frederik Grønhøj, University Hospital, Gentofte, Copenhagen

Brief Summary:
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 or disease Intervention/treatment Phase
Hepatic Insufficiency Drug: Alitretinoin Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: Pharmacokinetics of 9-cis-retinoic Acid (Alitretinoin, Toctino®) in Patients
Study Start Date : December 2010
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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®)

Primary Outcome Measures :
  1. 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 ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01261923

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Gentofte Hospital
Hellerup, Denmark, 2900
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
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Principal Investigator: Frederik Grønhøj, MD DMSci Gentofte Hospital
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Responsible Party: Frederik Grønhøj, MD, University Hospital, Gentofte, Copenhagen Identifier: NCT01261923    
Other Study ID Numbers: Eudra CT 2010-020212-11
First Posted: December 17, 2010    Key Record Dates
Last Update Posted: January 29, 2013
Last Verified: January 2013
Additional relevant MeSH terms:
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Hepatic Insufficiency
Liver Failure
Liver Diseases
Digestive System Diseases
Antineoplastic Agents
Dermatologic Agents