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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency
• Intervention / Treatment: Drug: Alitretinoin

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: 9-cis-retinoic-acid (9-cis-RA)(Alitretinoin, Toctino®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The investigators wish to investigate whether the metabolism of alitretinoin differs between healthy controls and patients with moderate to severe hepatic disease	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.	2 years

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Frederik Grønhøj, MD DMSci, Gentofte Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 16, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Estimate): January 29, 2013
• Last Update Submitted That Met QC Criteria: January 26, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Antineoplastic Agents; Dermatologic Agents; Alitretinoin
• Other Study ID Numbers: Eudra CT 2010-020212-11