Effect of Moderate Hepatic Impairment on the Pharmacokinetics and Metabolism of a Single Dose of Licarbazepine

NCT00424671 | Completed Phase 1

• 1 other identifier: CLIC477D2310
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the influence of moderate hepatic impairment on the pharmacokinetics of licarbazepine after single oral administration in healthy subjects and in subjects with stable impaired hepatic function.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• Influence of moderate hepatic impairment on the pharmacokinetics of

• licarbazepine after single oral administration of 1000 mg licarbazepine (given as 2 x 500

• mg IR tablets) in healthy subjects and in moderate hepatic impaired subjects

Secondary Outcomes (5)

• Influence of moderate hepatic impairment on the pharmacokinetics of the two enantiomers of licarbazepine and the glucuronide conjugates of licarbazepine and its

• two enantiomers after single oral administration of 1000 mg licarbazepine (given as 2 x

• 500 mg IR tablets) in healthy subjects and in moderate hepatic impaired subjects

• Safety and tolerability of single oral doses of 1000 mg licarbazepine (given

• as 2 x 500 mg IR tablets) in healthy subjects and in moderate hepatic impaired subjects

Interventions

Licarbazepine DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Control group and hepatically impaired groups:
• Able to communicate well with the investigator, to understand and comply with the requirements of the study. The subjects must be able to provide written informed consent prior to study participation, thus excluding subjects with encephalopathy grade 3 or 4.
• Body mass index (BMI) must be within the range of 18 to 32. For instructions and tables see Appendix 5.
• Hepatically impaired group:
• Subjects must have liver cirrhosis (hepatic fibrosis with evidence of either micro- or macro-nodular regeneration) confirmed by imaging techniques, ultrasound, MRI or CT.
• Subjects must have physical signs consistent with a clinical diagnosis of liver cirrhosis (e.g., liver firmness to palpation, splenic enlargement, spider angiomata, palmar erythema, parotid hypertrophy, testicular atrophy, gynecomastia).
• Subjects must have a Child-Pugh Clinical Assessment Score between 7 and 9 at both screening and baseline.
• Vital signs (after 3 minutes resting in a supine position) which are within the following ranges: oral body temperature between 35.0-37.5 °C systolic blood pressure, 100-180 mm Hg diastolic blood pressure, 60-115 mm Hg pulse rate, 60 - 100 bpm
• Subjects with creatinine clearance greater than 50 mL/min (based on Cockcroft and Gault formula)
• Control group:
• Subjects must be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• Subjects should be matched to the hepatically impaired group in gender, age (±10%), smoking status, BMI (±10%).
• At Screening, and Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed after the subject has rested for at least three (3) minutes, and again when required after three (3) minutes in the standing position. Vital signs should be within the following ranges: oral body temperature between 35.0-37.5 °C systolic blood pressure, 90-140 mm Hg diastolic blood pressure, 50-90 mm Hg pulse rate, 40 - 90 bpm When blood pressure and pulse will be taken again after 3 minutes standing, there shall be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (\>20 bpm) associated with clinical manifestation of postural hypotension. All blood pressure measurements at other time-points should be assessed with the subject supine, unless stated otherwise in the protocol design, and utilizing the same arm for each determination.

You may not qualify if:

• Control group and hepatically impaired group:
• Participation in any clinical investigation with experimental drug therapy within four weeks prior to dosing or longer as required by local regulation.
• Donation or loss of 400 mL or more of blood within two months prior to dosing.
• Significant acute, new onset illness (ie, flu, gastroenteritis) within two weeks prior to dosi4. A past medical history or clinically significant ECG abnormalities or a family history (grandparents, parents and siblings) of a prolonged QT-interval syndrome.
• History of hyponatremia or seizures.
• History of autonomic dysfunction.
• Subjects with a consistent, abnormally low total lymphocyte count (\< 10% of total white blood cell counts)
• A known hypersensitivity to the drug.
• History of immunocompromise, including a positive HIV (ELISA and Western blot) test result.
• Evidence of active alcohol or drug abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.
• Smokers who report cigarette use of more than 20 cigarettes per day. Urine cotinine levels will be measured during screening.
• Hepatically impaired group:
• Subjects with a history of unstable, severe, or clinically significant cardiovascular disease
• Subjects with clinically significant abnormal findings, not consistent with underlying disease, upon physical examination, ECG or laboratory evaluation.
• Subjects with frank symptoms of encephalopathy or ataxia.

Sponsors & Collaborators

• Novartis: lead

Study Sites (1)

Novartis Investigative site

Prague, Czechia

Location

MeSH Terms

Interventions

10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide

Study Officials

• Novartis

  Investigative site

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 18, 2007
• First Posted: January 19, 2007
• Study Start: November 1, 2006
• Last Updated: June 22, 2007

Record last verified: 2007-06

Locations

CZ (1)