Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 18 for:    "Basal Ganglia Disease" | "Benserazide"

Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics With a Single-dose of Levodopa/Benserazide 200/50 mg or With a Single-dose of Levodopa/Benserazide 200/50 mg Plus a Single-dose of Nebicapone 150 mg

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03097211
Recruitment Status : Completed
First Posted : March 31, 2017
Last Update Posted : March 31, 2017
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.

Brief Summary:
The purpose of this study was to determine whether the administration of BIA 6-512 (25 mg, 50 mg, 75 mg and 100 mg) at steady-state affects the pharmacokinetics of levodopa when administered in combination with a single-dose of immediate release levodopa/benserazide 200/50 mg or with a single-dose of immediate release levodopa/benserazide 200/50 mg plus a single-dose of nebicapone 150 mg.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Placebo Drug: BIA 6-512 Drug: Madopar® 250 Drug: Nebicapone Phase 1

Detailed Description:
Single centre, double-blind, randomised, placebo-controlled, rising multiple dose study in four sequential groups of healthy male and female subjects. Eligible subjects were admitted to the Human Pharmacology Unit (UFH)on the day prior to receiving the first study medication. Starting in the morning of Day 1 (first dose), subjects received BIA 6-512/Placebo thrice daily until the morning of Day 5 (last dose). Concomitantly with the morning dose of BIA 6-512/Placebo on Day 4, a levodopa/benserazide 200/50 mg (Madopar® 250) single-dose was administered. On Day 5, a Madopar® 250 single-dose and a nebicapone 150 mg single-dose were administered concomitantly with the morning dose of BIA 6-512/Placebo. In the morning of Day 4 and Day 5, products were administered in fasting conditions of at least 8 hours and subjects remained fasted until 2 h post-dose. Subjects were resident in the UFH from admission (Day 0) until at least 24 h post last dose (Day 6); then, they were discharged and returned for the follow-up visit.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study in Healthy Volunteers to Investigate the Effect of BIA 6-512 at Steady-state on the Levodopa Pharmacokinetics When Administered in Combination With a Single-dose of Levodopa/Benserazide 200/50 mg or With a Single-dose of Levodopa/Benserazide 200/50 mg Plus a Single-dose of Nebicapone 150 mg
Actual Study Start Date : July 17, 2006
Actual Primary Completion Date : October 20, 2006
Study Completion Date : October 20, 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Levodopa

Arm Intervention/treatment
Experimental: Group 1: BIA 6-512 25 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
Drug: Placebo
Placebo capsules. Orally, with 240 mL of potable water.

Drug: BIA 6-512
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg. Orally, with 240 mL of potable water.
Other Name: Trans-resveratrol

Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg. Orally, with 240 mL of potable water.
Other Name: Levodopa/benserazide

Drug: Nebicapone
Nebicapone 150 mg tablets. Orally, with 240 mL of potable water.
Other Name: BIA 3-202

Experimental: Group 2: BIA 6-512 50 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
Drug: Placebo
Placebo capsules. Orally, with 240 mL of potable water.

Drug: BIA 6-512
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg. Orally, with 240 mL of potable water.
Other Name: Trans-resveratrol

Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg. Orally, with 240 mL of potable water.
Other Name: Levodopa/benserazide

Drug: Nebicapone
Nebicapone 150 mg tablets. Orally, with 240 mL of potable water.
Other Name: BIA 3-202

Experimental: Group 3: BIA 6-512 75 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
Drug: Placebo
Placebo capsules. Orally, with 240 mL of potable water.

Drug: BIA 6-512
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg. Orally, with 240 mL of potable water.
Other Name: Trans-resveratrol

Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg. Orally, with 240 mL of potable water.
Other Name: Levodopa/benserazide

Drug: Nebicapone
Nebicapone 150 mg tablets. Orally, with 240 mL of potable water.
Other Name: BIA 3-202

Experimental: Group 4: BIA 6-512 100 mg or placebo
Subjects were administered with those investigational products at approximately 8-h intervals, starting in the morning (approximately at 8h00) of Day 1 and finishing in the morning of Day 5 (last dose). On Day 4, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 was administered. On Day 5, concomitantly with the BIA 6-512/Placebo morning dose, one tablet of Madopar® 250 and one tablet of nebicapone 150 mg were administered
Drug: Placebo
Placebo capsules. Orally, with 240 mL of potable water.

Drug: BIA 6-512
The investigational products consisted of capsules containing BIA 6-512 25 mg, 50 mg, 75 mg, 100 mg. Orally, with 240 mL of potable water.
Other Name: Trans-resveratrol

Drug: Madopar® 250
Levodopa/benserazide immediate release tablets 200mg/50mg. Orally, with 240 mL of potable water.
Other Name: Levodopa/benserazide

Drug: Nebicapone
Nebicapone 150 mg tablets. Orally, with 240 mL of potable water.
Other Name: BIA 3-202




Primary Outcome Measures :
  1. Day 4 - Maximum observed plasma drug concentration (Cmax) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose. ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4

  2. Day 4 - Time of occurrence of Cmax (tmax) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose. ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4

  3. Day 4 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose. ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4

  4. Day 4 - AUC from time zero to 8 h post-dose (AUC0-τ) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose. ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4

  5. Day 4 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose. ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4

  6. Day 4 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8 and 16 hours post-dose. ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 4

  7. Day 5 - Maximum observed plasma drug concentration (Cmax) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5

  8. Day 5 - Time of occurrence of Cmax (tmax) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5

  9. Day 5 - Area under the plasma concentration-time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5

  10. Day 5 - AUC from time zero to 8 h post-dose (AUC0-τ) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5

  11. Day 5 - Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5

  12. Day 5 - Apparent terminal elimination half-life, calculated from ln 2/λz (t1/2) [ Time Frame: pre-dose, ¼, ½, ¾, 1, 1½, 2, 3, 4, 6, 8, 16 and 24 hours post-dose ]
    Pharmacokinetic parameters of BIA 6-512, levodopa, and nebicapone on day 5



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female subjects aged between 18 and 45 years, inclusive.
  • Subjects of body mass index (BMI) between 19 and 30 kg/m2, inclusive.
  • Subjects who were healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG.
  • Subjects who had negative tests for HBsAg, anti-HCVAb and HIV-1 and HIV-2 Ab at screening
  • Subjects who had clinical laboratory test results clinically acceptable at screening and admission.
  • Subjects who had a negative screen for alcohol and drugs of abuse at screening and admission.
  • Subjects who were non-smokers or who smoked ≤ 10 cigarettes or equivalent per day.
  • Subjects who were able and willing to gave written informed consent.
  • (If female) She was not of childbearing potential by reason of surgery or, if of childbearing potential, she used one of the following methods of contraception: double barrier, intrauterine device or abstinence.
  • (If female) She had a negative urine pregnancy test at screening and admission.

Exclusion Criteria:

  • Subjects who had a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine, connective tissue diseases or disorders.
  • Subjects who had a clinically relevant surgical history.
  • Subjects who had a clinically relevant family history.
  • Subjects who had a history of relevant atopy.
  • Subjects who had a history of relevant drug hypersensitivity.
  • Subjects who had a history of alcoholism or drug abuse.
  • Subjects who consumed more than 14 units of alcohol a week.
  • Subjects who had a significant infection or known inflammatory process on screening or admission.
  • Subjects who had acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea, heartburn) at the time of screening or admission.
  • Subjects who had used medicines within 2 weeks of admission that may affect the safety or other study assessments, in the investigator's opinion.
  • Subjects who had previously participated in a clinical trial with BIA 6-512.
  • Subjects who had used any investigational drug or participated in any clinical trial within 6 months prior to screening.
  • Subjects who had participated in more than 2 clinical trials within the 12 months prior to screening.
  • Subjects who had donated or received any blood or blood products within the 3 months prior to screening.
  • Subjects who were vegetarians, vegans or have medical dietary restrictions.
  • Subjects who cannot communicate reliably with the investigator.
  • Subjects who were unlikely to co-operate with the requirements of the study.
  • Subjects who were unwilling or unable to give written informed consent.
  • (If female) She was pregnant or breast-feeding.
  • (If female) She was of childbearing potential and she did not use an effective contraceptive method (double-barrier, intra-uterine device or abstinence) or she used oral contraceptives.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03097211


Locations
Layout table for location information
Portugal
Human Pharmacology Unit (UFH) - BIAL - Portela & Cª, SA
S. Mamede do Coronado, Portugal, 4745-457
Sponsors and Collaborators
Bial - Portela C S.A.

Layout table for additonal information
Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT03097211     History of Changes
Other Study ID Numbers: BIA-6512-107
First Posted: March 31, 2017    Key Record Dates
Last Update Posted: March 31, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Basal Ganglia Diseases
Benserazide
Benserazide, levodopa drug combination
Parkinson Disease
Parkinsonian Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Enzyme Inhibitors