Clinical trial NCT02281422: An Open-label, Single-dose, Single-centre Study, Investigating the Pharmacokinetics of BIA 2-093
Official title: An Open-label, Single-dose, Single-centre Study, Investigating the Pharmacokinetics of BIA 2-093 in Subjects With Various Degrees of Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Epilepsy
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2014-11-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax - Peak Plasma Concentration
timeFrame: 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.
measure: AUC(0-12h) - AUC From Time Zero to 12h
timeFrame: 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 outcomes:
measure: Tmax (hr) - Time at Which Cmax Occurred
timeFrame: 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.
Other outcomes:
Locations:
city: Bloemfontein
country: South Africa
facility: Farmovs-Parexel
Study officials:
References: