An Open-label, Single-dose, Single-centre Study, Investigating the Pharmacokinetics of BIA 2-093

An Open-label, Single-dose, Single-centre Study, Investigating the Pharmacokinetics of BIA 2-093 in Subjects With Various Degrees of Renal Impairment

Open-label, single-dose (BIA 2-093 800 mg tablet), single-centre study in five groups of subjects with various degrees of renal function based on creatinine clearance

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: BIA 2-093

Detailed Description

This was an open-label, single-dose (BIA 2-093 800 mg tablet), single-centre study in five groups of subjects with various degrees of renal function based on creatinine clearance (stages of renal function according to the Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products Guidelines) for the evaluation of pharmacokinetics in patients with impaired renal function.

The trial commenced with Groups 1 and 2. An interim safety evaluation was conducted and, as there were no safety concerns, the trial continued with Groups 3 and 4. After another interim safety evaluation with the data from Groups 3 and 4, the trial commenced with Group 5.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Bloemfontein, South Africa, 9301
    • Farmovs-Parexel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females at least 18 years of age, with body mass not less than 50 kg.
• Female subjects had to be post-menopausal, surgically sterilized or using a reliable method of contraception.
• Subjects suffering from a chronic illness, other than hepatic impairment, had to have a stable condition, regarded by the investigator as unlikely to influence the outcome of the study.
• Renal failure, the extent of which, as measured by the creatinine clearance, resulted in recruitment to one of five renal function groups.
• Medical records indicating a stable serum creatinine (variation of not more than 30%), for at least 3 months prior to the screening visit (Groups 2 to 4 only), as determined by the clinical investigator. The sérum creatinine had to be stable to allow for an accurate determination of the creatinine clearance and therefore allowed for correct allocation to one of the renal function groups. Subjects who were recruited into Group 1 had normal renal function.

Exclusion Criteria:

• The receipt of any investigational drug within 30 days prior to this study.
• Clinically significant abnormal findings (as judged by the investigator) for the following parameters, except those consistent with findings in renal failure: haematology, biochemistry, clotting profile, urinalysis, vital signs or ECG screening tests.
• A history or laboratory evidence of hepatic impairment and/or disease. Owing to the metabolic pathway of BIA 2-093, any degree of hepatic impairment would have had a confounding effect on the PK analysis.
• Positive test for HIV-1 or HIV-2 Antibodies, Hepatitis B surface antigen and Hepatitis C Antibodies.

HIV positive patients, and patients with Hepatitis B and C, generally have a below average, and in some cases a markedly decreased, level of health owing to the nature of the respective infections and the natural course of the diseases, both of which are often complicated by an array of opportunistic illnesses. Their ill health would have been further worsened by the fact that the patients are invarious degrees of renal failure, which has its own, often debilitating, complications. If patients with HIV or Hepatitis B or C were included in the study, this could have led to statistical confusion when assessing the safety and tolerability parameters. This is because events reported by the patients, which may be a part of the spectrum of complaints in HIV positive patients and Hepatitis B and C patients, would have confounded the safety and tolerability analysis. Furthermore, Hepatitis B and C, which may cause an element of hepatic impairment, would have confounded the PK analysis due to the metabolic pathway of BIA 2-093. In addition, by administering the study medication to these subjects, any adverse events that might have occurred would have added to the discomfort of the patient.

• A history of any illness that, in the opinion of the Investigator and/or Sponsor, might have confounded the results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group 1 normal renal function; normal renal function (creatinine clearance > 80 mL/min)	Drug: BIA 2-093
Other: Group 2 mild renal impairment; mild renal impairment (creatinine clearance 50-80 mL/min)	Drug: BIA 2-093
Other: Group 3 moderate renal impairment; moderate renal impairment (creatinine clearance 30-50 mL/min)	Drug: BIA 2-093
Other: Group 4 severe renal impairment; severe renal impairment (creatinine clearance <30 mL/min)	Drug: BIA 2-093
Other: Group 5 end stage renal disease; end stage renal disease, requiring haemodialysis (ESRD)	Drug: BIA 2-093

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax - Peak Plasma Concentration	BIA 2-194; BIA 2-195; Oxcarbazepine are BIA 2-093 metabolites	pre-dose and 1, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 7, 9, 12, 24, 48, 72 and 96 hours post-dose.
AUC(0-12h) - AUC From Time Zero to 12h	BIA 2-194; BIA 2-195; Oxcarbazepine are BIA 2-093 metabolites AUC - area under the plasma concentration versus time curve	pre-dose and 1, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 7, 9, 12, 24, 48, 72 and 96 hours post-dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax (hr) - Time at Which Cmax Occurred	BIA 2-194; BIA 2-195; Oxcarbazepine are BIA 2-093 metabolites Cmax - maximum observed plasma drug concentration	pre-dose and 1, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 7, 9, 12, 24, 48, 72 and 96 hours post-dose.

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: October 30, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (Estimate): November 2, 2014

Study Record Updates

• Last Update Posted (Estimate): December 31, 2014
• Last Update Submitted That Met QC Criteria: December 18, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Eslicarbazepine acetate
• Other Study ID Numbers: BIA-2093-112