Study to Evaluate the Pharmacokinetics, Safety, Tolerability of Single Dose Lacosamide in Subjects With Renal Impairment Compared to Healthy Subjects

UCB

Status and phase

Completed

Phase 1

Conditions

Renal Impairment

Healthy

Treatments

Drug: Lacosamide tablet

Study type

Interventional

Funder types

Industry

Identifiers

NCT01796938

SP0641

Details and patient eligibility

About

To investigate the Pharmacokinetics (PK) of oral administered Lacosamide in renal impaired subjects and healthy subjects.

Enrollment

40 patients

Sex

All

Ages

18 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Subject was informed and given ample time and opportunity to think about his/her participation and had given his/her written informed consent
Subject was willing and able to comply with all trial requirements
Subject was a male or female Caucasian, between 18 and 70 years of age (inclusive)
If female, subject was of non-childbearing potential (post-menopausal or hysterectomized) or was using medically adequate contraception
If female of childbearing potential, subject had a negative pregnancy test
Subject had a Body Mass Index (BMI) between 20 and 34 kg/m2 (inclusive)
Subject was healthy without clinically relevant cardiovascular, renal, gastrointestinal, hepatic, metabolic, endocrine, neurological, or psychiatric abnormalities detected during Eligibility Assessment (EA)

Subjects with renal impairment also had to fulfill the following inclusion criteria:

Subject had no clinically relevant cardiovascular or endocrine findings during EA
Subject had a renal impairment. The subjects were assigned to 1 of the following treatment groups according to Creatinine Clearance (CLCr) values determined 2 to 7 days prior to dosing:
Group 2: 80 mL/min > CLCr ≥ 50 mL/min (subjects with mild renal impairment)
Group 3: 50 mL/min > CLCr ≥ 30 mL/min (subjects with moderate renal impairment)
Group 4: CLCr < 30 mL/min (subjects with severe renal impairment, not on dialysis between 2 weeks before EA and end of the trial)

Inclusion criteria for Group 5:

Subject was informed and given ample time and opportunity to think about his/her participation and had given his/her written informed consent
Subject was willing and able to comply with all trial requirements
Subject was a male or female Caucasian, between 18 and 70 years of age (inclusive)
If female, subject was of non-childbearing potential (post-menopausal or hysterectomized) or was using medically adequate contraception
If female of childbearing potential, subject had a negative pregnancy test
Subject had a BMI between 20 and 34 kg/m2 (inclusive)
Subject had no clinically relevant cardiovascular or endocrine findings during EA
Subject had an endstage renal disease (CLCr < 15 mL/min, determined approximately 2 to 7 days before first dosing) treated with extracorporal hemodialysis for at least 4 months

Exclusion criteria

Healthy subjects:

Subject had previously participated in this trial
Subject had participated in another trial of an investigational product within the last 3 months or was currently participating in another trial of an investigational product
Subject had donated blood or had a comparable blood loss (> 500 mL) within the last 3 months prior to EA
Subject smoked more than 5 cigarettes per day or had done so within the 6 months prior to commencement of this trial
Subject had a history of chronic alcohol or drug abuse within the last 6 months prior to commencement of this trial
Subject consumed more than 40 g of alcohol/day (amount corresponds to 1 L beer/day or 0.5 L wine/day or 120 mL liquor/day)
Subject had positive tests for alcohol (urine or breath test) or drugs (urine test)
Subject had clinically relevant changes in the electrocardiogram (ECG), such as second- or third-degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms or of the corrected QT (QTc) interval > 430 ms (male subjects) or > 450 ms (female subjects)
Subject had a history or present condition of clinically relevant respiratory or cardiovascular disorders, eg, cardiac insufficiency, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia, or status after myocardial infarction
Subject had a history or present condition of psychic abnormality, psychiatric or neurologic illness, or autonomic neuropathy that, in the opinion of the Investigator, could have jeopardized or would have compromised the subject's ability to participate in the trial
Subject had a history or present condition of seizure disorder
Subject had a history or present condition of malignancy
Subject had a history or present condition of renal disorders (albuminuria, chronic infections) or renal impairment
Subject had a history or present condition of Diabetes Mellitus or thyroid dysfunction, especially Hyperthyreosis, or other endocrine disorders
Subject had a clinically relevant allergy
Subject had a known or suspected drug hypersensitivity, in particular to the trial medication
Subject was taking any concomitant medication currently or within 2 weeks prior to the first day of dosing (with the exception of oral contraceptives and Paracetamol [maximum allowed dose: 1000 mg/dose], which were allowed up to 48 hours prior to dosing); further exceptions could be made if the Investigator and the sponsor jointly considered the medication as acceptable
Subject was tested positive for human immunodeficiency virus 1/2 antibodies (HIV-1/2-Ab), hepatitis B surface antigen (HBs-Ag), or hepatitis C virus antibody (HCV-Ab)
Subject had any clinically relevant abnormality in the physical examination or in vital sign measurements (systolic blood pressure > 150 mmHg or < 100 mmHg, diastolic blood pressure > 95 mmHg or < 60 mmHg, pulse rate > 100 beats per minute (bpm) or < 50 bpm)
Subject had a clinically relevant deviation from the norm in the clinical chemistry, hematology, or urinalysis evaluations

Exclusion criteria for Groups 2-4:

Exclusion criteria 1 to 12 for healthy subjects also applied to subjects with renal impairment
Subject had a clinically relevant allergy
Subject had a known or suspected drug hypersensitivity, in particular to the trial medication
Subject was taking any concomitant medication currently or within 2 weeks prior to dosing that could have interfered with the investigational product
Subject was tested positive for HIV-1/2-Ab, HBs-Ag, or HCV-Ab
Subject had any clinically relevant abnormality in the physical examination or in vital sign measurements (systolic blood pressure > 180 mmHg or < 100 mmHg, diastolic blood pressure > 110 mmHg, pulse rate > 100 bpm or < 60 bpm)
Subject had a clinically relevant deviation from the norm in the clinical chemistry, hematology or urinalysis evaluations other than expected for a subject with renal impairment, eg, hemoglobin < 8.0 g/dL

Exclusion criteria for Group 5:

Exclusion criteria 1 to 12 for healthy subjects also applied to subjects in Group 5
Subject had a clinically relevant allergy
Subject had a known or suspected drug hypersensitivity, in particular to the trial medication
Subject was tested positive for HIV-1/2-Ab, HBs-Ag, or HCV-Ab
Subject was taking any concomitant medication that might interfere with the investigational product currently or within 2 weeks prior to dosing
Subject had any clinically relevant abnormality in the physical examination or in vital sign measurements (systolic blood pressure > 200 mmHg [predialysis value] or < 100 mmHg, diastolic blood pressure > 110 mmHg, pulse rate > 100 bpm or < 60 bpm)
Subject had a clinically relevant deviation from the norm in the clinical chemistry, hematology, or urinalysis evaluations other than expected for a patient with renal impairment, eg, hemoglobin < 8.0 g/dL

Trial design

40 participants in 5 patient groups

Group 1: Healthy subjects

Experimental group

Description: