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A Open-label, Drug Interaction Study Between Eslicarbazepine Acetate and Topiramate

Sponsor
Bial - Portela C S.A. (Industry)
Overall Status
Completed
CT.gov ID
NCT02283814
Collaborator
(none)
32
Enrollment
2
Arms
1
Duration (Months)

Study Details

Study Description

Brief Summary

Single centre, open-label, multiple doses, one-sequence design study in two parallel groups of healthy volunteers

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Single centre, open-label, multiple doses, one-sequence design study in two parallel groups of healthy volunteers: Group A: Pre-treatment with ESL, treatment with ESL and ascending doses of Topamax (TPM) in last phases; Group B: Pre-treatment with TPM, treatment with TPM and ascending doses of ESL in last phases

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase-1, Open-label, Drug Interaction Study Between Eslicarbazepine Acetate 1200 mg and Topiramate 200 mg Following Multiple Dose Administrations in Healthy Male
Study Start Date :
Jan 1, 2007
Actual Primary Completion Date :
Feb 1, 2007
Actual Study Completion Date :
Feb 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group A BIA 2-093 + Topamax

Group A Pre-treatment: 600 mg once daily dose of eslicarbazepine acetate (ESL) administered for two consecutive days; Treatment 1: 1200 mg once daily dose of eslicarbazepine acetate (ESL) administered for six consecutive days Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg (morning) + 100mg (evening) for two consecutive days Treatment 4: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200 mg for fifteen consecutive days

Drug: BIA 2-093
Other Names:
  • ESL, Eslicarbazepine acetate

    • Drug: Topamax
    Other Names:
  • TPM

    		•
    Experimental: Group B BIA 2-093 + Topamax

    Pre-treatment: 100 mg once daily dose of TPM administered for two consecutive days; Pre-treatment 2: 100 mg twice daily dose of TPM administered for two consecutive days; Treatment: 200 mg once daily dose of TPM administered for four consecutive days; Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 600 mg and TPM 200 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200mg for seventeen consecutive days

    Drug: BIA 2-093
    Other Names:
  • ESL, Eslicarbazepine acetate

    • Drug: Topamax
    Other Names:
  • TPM

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Cmax - the Maximum Plasma Concentration [Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h]

      BIA 2-194 and BIA 2-195 are metabolites/active forms of eslicarbazepine acetate

    2. Tmax - the Time of Occurrence of Cmax [Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h]

      BIA 2-194 and BIA 2-195 are metabolites/active forms of eslicarbazepine acetate Both Groups A and B described in participant flow recieved BIA 2-093 and Topiramate. The results presented here are related with the different interventions in both groups

    Secondary Outcome Measures

    1. AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State. [Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Availability of volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer

    • Male aged of at least 18 years but not older than 45 years with a body mass índex (BMI) greater than or equal to 19 and below 30 kg/m

    • Clinical laboratory values within the laboratory's stated normal range; i f not within this range, they must be without any clinical significance (laboratory tests are presented in section 6.1.1.3)

    • Healthy according to the medical history, laboratory results and physical

    • Light-, non- or ex-smokers. A light smoker is defined as someone smoking 1 0 cigarettes or less per day, and an ex-smoker i s defined as someone who completely stopped smoking for at least 1 2 months before day 1 of this study

    Exclusion Criteria:

    • Significant history of hypersensitivity to topiramate, eslicarbazepine, oxcarbazepine, carbamazepine or any related products (including excipients of the formulations) as wel l as severe hypersensitivity reactions (like angioedema) to any drugs

    • Presence of significant gastrointestinal, l iver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects

    • History of significant gastrointestinal, liver o r kidney disease, o r surgery that may affect drug bioavailability, including but not limited to cholecystectomy

    • Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic d isease

    • Presence o f significant heart disease o r disorder according to ECG

    • Presence or history of significant central nervous system disorder l ike convulsion or depression

    • Presence o r history o f significant ocular disease

    • Presence or history of severe hepatic impairment

    • Presence or history of renal insufficiency (serum creatinine level greater than 135 μmol/L)

    • History or presence of acidosis

    • Use of valproic acid in the previous 7 days prior to Day 1 of the study.

    • Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)

    • Any clinically significant illness in the previous 28 days before day 1 of this study

    • Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin and rifampin), in the previous 28 days before Day 1 of this study

    • Participation in another clinical trial or donation of 50 mL or more of blood in the previous 28 days before day 1 of this study

    • Donation of 500 mL or more of blood (Canadian B lood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study

    • Positive urine screening of drugs of abuse (drugs listing is presented in section 6.1.1.4).

    • Positive results to HIV, HBsAg or anti-HCV tests

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Bial - Portela C S.A.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bial - Portela C S.A.
    ClinicalTrials.gov Identifier:
    NCT02283814
    Other Study ID Numbers:
    • BIA-2093-120
    First Posted:
    Nov 5, 2014
    Last Update Posted:
    Dec 22, 2014
    Last Verified:
    Dec 1, 2014
    Additional relevant MeSH terms:
    Epilepsy
    Topiramate
    Eslicarbazepine acetate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Group A BIA 2-093 + Topamax Group B BIA 2-093 + Topamax
    Arm/Group Description Group A Pre-treatment: 600 mg once daily dose of eslicarbazepine acetate (ESL) administered for two consecutive days; Treatment 1: 1200 mg once daily dose of eslicarbazepine acetate (ESL) administered for six consecutive days Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg (morning) + 100mg (evening) for two consecutive days Treatment 4: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200 mg for fifteen consecutive days BIA 2-093 Topamax Pre-treatment: 100 mg once daily dose of TPM administered for two consecutive days; Pre-treatment 2: 100 mg twice daily dose of TPM administered for two consecutive days; Treatment: 200 mg once daily dose of TPM administered for four consecutive days; Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 600 mg and TPM 200 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200mg for seventeen consecutive days BIA 2-093 Topamax
    Period Title: Overall Study
    STARTED 16 16
    COMPLETED 13 14
    NOT COMPLETED 3 2

    Baseline Characteristics

    Arm/Group Title Group A BIA 2-093 + Topamax Group B BIA 2-093 + Topamax Total
    Arm/Group Description Group A Pre-treatment: 600 mg once daily dose of eslicarbazepine acetate (ESL) administered for two consecutive days; Treatment 1: 1200 mg once daily dose of eslicarbazepine acetate (ESL) administered for six consecutive days Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg (morning) + 100mg (evening) for two consecutive days Treatment 4: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200 mg for fifteen consecutive days BIA 2-093 Topamax Pre-treatment: 100 mg once daily dose of TPM administered for two consecutive days; Pre-treatment 2: 100 mg twice daily dose of TPM administered for two consecutive days; Treatment: 200 mg once daily dose of TPM administered for four consecutive days; Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 600 mg and TPM 200 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200mg for seventeen consecutive days BIA 2-093 Topamax Total of all reporting groups
    Overall Participants 13 14 27
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    13
    100%
    14
    100%
    27
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    13
    100%
    14
    100%
    27
    100%

    Outcome Measures

    1. Primary Outcome
    Title Cmax - the Maximum Plasma Concentration
    Description BIA 2-194 and BIA 2-195 are metabolites/active forms of eslicarbazepine acetate
    Time Frame Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BIA 2-093 + TPM BIA 2-093
    Arm/Group Description BIA 2-093 - ESL; Eslicarbazepine acetate TPM - Topamax BIA 2-093 - ESL; Eslicarbazepine acetate
    Measure Participants 27 16
    Cmax (BIA 2-194)
    21960.6
    (2482)
    25414.8
    (3736)
    Cmax (BIA 2-195)
    931.8
    (216)
    1062.6
    (235)
    2. Primary Outcome
    Title Tmax - the Time of Occurrence of Cmax
    Description BIA 2-194 and BIA 2-195 are metabolites/active forms of eslicarbazepine acetate Both Groups A and B described in participant flow recieved BIA 2-093 and Topiramate. The results presented here are related with the different interventions in both groups
    Time Frame Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BIA 2-093 + TPM BIA 2-093
    Arm/Group Description BIA 2-093 - ESL; Eslicarbazepine acetate TPM - Topamax BIA 2-093 - ESL; Eslicarbazepine acetate
    Measure Participants 27 16
    Tmax (BIA 2-194)
    2.00
    (0.96)
    2.00
    (0.97)
    Tmax (BIA 2-195)
    9.00
    (4.20)
    6.00
    (3.91)
    3. Secondary Outcome
    Title AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State.
    Description
    Time Frame Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BIA 2-093 + TPM BIA 2-093
    Arm/Group Description BIA 2-093 - ESL; Eslicarbazepine acetate TPM - Topamax BIA 2-093 - ESL; Eslicarbazepine acetate
    Measure Participants 27 16
    AUCτ (BIA 2-194)
    361733.9
    (38706)
    389794.3
    (35861)
    AUCτ (BIA 2-195)
    19611.8
    (4707)
    22886.8
    (5195)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Group A BIA 2-093 + Topamax Group B BIA 2-093 + Topamax
    Arm/Group Description Group A Pre-treatment: 600 mg once daily dose of eslicarbazepine acetate (ESL) administered for two consecutive days; Treatment 1: 1200 mg once daily dose of eslicarbazepine acetate (ESL) administered for six consecutive days Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 100 mg (morning) + 100mg (evening) for two consecutive days Treatment 4: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200 mg for fifteen consecutive days BIA 2-093 Topamax Pre-treatment: 100 mg once daily dose of TPM administered for two consecutive days; Pre-treatment 2: 100 mg twice daily dose of TPM administered for two consecutive days; Treatment: 200 mg once daily dose of TPM administered for four consecutive days; Treatment 2: Concomitant doses of eslicarbazepine acetate (ESL) 600 mg and TPM 200 mg for two consecutive days Treatment 3: Concomitant doses of eslicarbazepine acetate (ESL) 1200 mg and TPM 200mg for seventeen consecutive days BIA 2-093 Topamax
    All Cause Mortality
    Group A BIA 2-093 + Topamax Group B BIA 2-093 + Topamax
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Group A BIA 2-093 + Topamax Group B BIA 2-093 + Topamax
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Group A BIA 2-093 + Topamax Group B BIA 2-093 + Topamax
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/16 (93.8%) 13/16 (81.3%)
    Cardiac disorders
    Palpitations 1/16 (6.3%) 0/16 (0%)
    Ear and labyrinth disorders
    Ear pain 0/16 (0%) 1/16 (6.3%)
    Eye disorders
    dry eye 1/16 (6.3%) 1/16 (6.3%)
    Ocular hyperaemia 1/16 (6.3%) 0/16 (0%)
    Eye pain 0/16 (0%) 1/16 (6.3%)
    Photophobia 0/16 (0%) 2/16 (12.5%)
    Visual disturbance 0/16 (0%) 1/16 (6.3%)
    Gastrointestinal disorders
    Abdominal distension 1/16 (6.3%) 7/16 (43.8%)
    Abdominal pain upper 1/16 (6.3%) 1/16 (6.3%)
    Constipation 4/16 (25%) 2/16 (12.5%)
    Diarrheoa 1/16 (6.3%) 2/16 (12.5%)
    Flatulence 2/16 (12.5%) 3/16 (18.8%)
    hypoaesthesia teeth 1/16 (6.3%) 0/16 (0%)
    Lip dry 5/16 (31.3%) 6/16 (37.5%)
    Reflux gastritis 1/16 (6.3%) 0/16 (0%)
    Tongue coated 1/16 (6.3%) 0/16 (0%)
    Abdominal pain 0/16 (0%) 3/16 (18.8%)
    Dyspepsia 0/16 (0%) 2/16 (12.5%)
    Gingival bleeding 0/16 (0%) 1/16 (6.3%)
    Nausea 0/16 (0%) 3/16 (18.8%)
    Oral pain 0/16 (0%) 1/16 (6.3%)
    Toothache 0/16 (0%) 1/16 (6.3%)
    General disorders
    Fatigue 5/16 (31.3%) 6/16 (37.5%)
    Feeling drunk 2/16 (12.5%) 0/16 (0%)
    Feeling hot 2/16 (12.5%) 0/16 (0%)
    hot flush 3/16 (18.8%) 1/16 (6.3%)
    Pyrexia 1/16 (6.3%) 0/16 (0%)
    Venipuncture site redness 1/16 (6.3%) 0/16 (0%)
    Vessel puncture site bruise 2/16 (12.5%) 0/16 (0%)
    Infections and infestations
    Oral herpes 0/16 (0%) 1/16 (6.3%)
    Injury, poisoning and procedural complications
    Injury 1/16 (6.3%) 3/16 (18.8%)
    Investigations
    Alanine aminotransferase increased 1/16 (6.3%) 0/16 (0%)
    Aspartate aminotransferase increased 1/16 (6.3%) 0/16 (0%)
    Red blood cells urine positive 1/16 (6.3%) 0/16 (0%)
    Blood pressure systolic increased 0/16 (0%) 2/16 (12.5%)
    Metabolism and nutrition disorders
    Decreased appetite 1/16 (6.3%) 2/16 (12.5%)
    Musculoskeletal and connective tissue disorders
    Arthalgia 1/16 (6.3%) 0/16 (0%)
    Back pain 3/16 (18.8%) 1/16 (6.3%)
    Limb discomfort 1/16 (6.3%) 0/16 (0%)
    Musculoskeletal pain 1/16 (6.3%) 0/16 (0%)
    Muscular weakness 1/16 (6.3%) 0/16 (0%)
    Myalgia 1/16 (6.3%) 2/16 (12.5%)
    Sensation of heaviness 1/16 (6.3%) 0/16 (0%)
    Muscular discomfort 0/16 (0%) 1/16 (6.3%)
    Muscular stiffness 0/16 (0%) 1/16 (6.3%)
    Nervous system disorders
    Coordination abnormal 1/16 (6.3%) 0/16 (0%)
    Disturbance in attention 4/16 (25%) 1/16 (6.3%)
    Dizziness 5/16 (31.3%) 1/16 (6.3%)
    Headache 7/16 (43.8%) 4/16 (25%)
    Somnolence 14/16 (87.5%) 13/16 (81.3%)
    Dysarthria 1/16 (6.3%) 0/16 (0%)
    Head discomfort 1/16 (6.3%) 0/16 (0%)
    Paraesthesia 1/16 (6.3%) 4/16 (25%)
    Paraesthesia oral 8/16 (50%) 3/16 (18.8%)
    Speech disorder 1/16 (6.3%) 0/16 (0%)
    Vision blurred 1/16 (6.3%) 4/16 (25%)
    Amnesia 0/16 (0%) 1/16 (6.3%)
    Coordination decreased 0/16 (0%) 1/16 (6.3%)
    Insomnia 0/16 (0%) 1/16 (6.3%)
    Sensing disturbance 0/16 (0%) 1/16 (6.3%)
    Psychiatric disorders
    Erection increased 1/16 (6.3%) 1/16 (6.3%)
    Euphoric mood 4/16 (25%) 3/16 (18.8%)
    Irritability 1/16 (6.3%) 0/16 (0%)
    Libido increased 1/16 (6.3%) 0/16 (0%)
    Mood altered 2/16 (12.5%) 1/16 (6.3%)
    Psychomotor retardation 2/16 (12.5%) 0/16 (0%)
    Agitation 0/16 (0%) 1/16 (6.3%)
    Anxiety 0/16 (0%) 1/16 (6.3%)
    Renal and urinary disorders
    Dysuria 1/16 (6.3%) 0/16 (0%)
    Pollakiuria 1/16 (6.3%) 0/16 (0%)
    Urine abnormality 0/16 (0%) 1/16 (6.3%)
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 1/16 (6.3%) 2/16 (12.5%)
    Nasal congestion 1/16 (6.3%) 0/16 (0%)
    Pharyngolaryngeal pain 2/16 (12.5%) 1/16 (6.3%)
    Upper repiratory tract infection 1/16 (6.3%) 2/16 (12.5%)
    Viral upper respiratory tract infection 1/16 (6.3%) 0/16 (0%)
    Skin and subcutaneous tissue disorders
    Dry skin 1/16 (6.3%) 2/16 (12.5%)
    Pruritus 1/16 (6.3%) 0/16 (0%)
    Rash 2/16 (12.5%) 0/16 (0%)
    Rash generalised 1/16 (6.3%) 0/16 (0%)
    Rash maculo-papular 2/16 (12.5%) 0/16 (0%)
    Skin irritation 0/16 (0%) 1/16 (6.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Head of Clinical Research
    Organization Bial - Portela & Cª, S.A.
    Phone +351 229 866 100
    Email jose.rocha@bial.com
    Responsible Party:
    Bial - Portela C S.A.
    ClinicalTrials.gov Identifier:
    NCT02283814
    Other Study ID Numbers:
    • BIA-2093-120
    First Posted:
    Nov 5, 2014
    Last Update Posted:
    Dec 22, 2014
    Last Verified:
    Dec 1, 2014