Clinical trial NCT02092168: Pharmacokinetics of BIA 9-1067 and Its Metabolites in Healthy Male Elderly Subjects and in Healthy Male Young Subjects
Official title: Single-dose and Steady-state Pharmacokinetics of BIA 9-1067 and Its Metabolites in Healthy Male Elderly Subjects Compared With Those in Healthy Male Young Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Keywords: Opicapone
BIAL
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2014-03-20
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects of age on the pharmacokinetic (PK) profile of BIA 9-1067 and its metabolites.

Detailed description: Methodology:

Single-centre, open-label, parallel group, non-randomised multiple-dose 7-day study in 12 healthy elderly and 12 healthy younger male subjects.

Duration of treatment:

Each subject participated in the study for approximately 6 weeks. Participation included a screening evaluation within 28 days before inpatient period, a 12 day inpatient period and an end of study visit (ESV) 7 to 10 days after the discharge from the Unit.

The study design followed the recommendations of the CPMP/ICH/379/95 (ICH Topic E7) Note for Guidance on Studies in Support of Special Populations: Geriatrics, namely in the inclusion of subjects aged 65 years or older and contemplating single-dose and steady-state PK profiles. As the primary endpoint of the study was to characterize the pharmacokinetic profile of BIA 9-1067 and its metabolites in different parallel groups, there was no need to implement blinding procedures or to include a control group. Consequently, the trial was an open label study. Healthy subjects rather than patients with Parkinson's disease have been chosen as the study population, due to the lack of over-toxicity of the drug and an acceptable risk-benefit ratio. This allowed for a better interpretation of the study results, as there were no confounding factors resulting from changes in disease state and or concomitant medications.

The subjects were given a screening number after signing the informed consent by chronological order of inclusion in each group (young/elderly).

Eligibility criteria: Inclusion Criteria:

All subjects (young and elderly):

1. A signed and dated informed consent form before any study-specific screening procedure is performed.
2. Healthy as determined by the investigator on the basis of medical history, physical examination, clinical laboratory test results, vital signs and digital 12-lead electrocardiogram (ECG).
3. Non-smoker or smoker of fewer than 10 cigarettes per day as determined by history. Had to be able to abstain from smoking during the inpatient stay.
4. With a body mass index (BMI) between 19 and 30 kg/m2, inclusive.

   Young subjects only:
5. Males aged between 18 and 40 years, inclusive.

   Elderly subjects only:
6. Males older than 65 years, inclusive.

Exclusion Criteria:

All subjects (young and elderly):

General

1. Subjects who had participated in a clinical trial with an investigational drug within the 90 days prior to screening.
2. Subjects who were likely to be noncompliant with the protocol, or who were felt to be unsuitable by the Investigator for any other reason.
3. Positive serologic findings for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
4. Positive findings of urine drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA \[3,4-ethylenedioxymethamphetamine; ecstasy\]).

   Medical History
5. Any significant cardiovascular, hepatic, renal, respiratory (e.g. childhood asthma), gastrointestinal, endocrine (e.g. diabetes,), immunological, dermatological, haematological, neurological, or psychiatric disease and history thereof.
6. Acute disease state (e.g., nausea, vomiting, fever, diarrhoea) within 7 days before study Day 1.
7. History of drug abuse within 1 year before study Day 1.
8. History of alcoholism within 1 year before Day 1. Consumption of more than 50 g of ethanol per day (12.5 cL glass of 10° \[10%\] wine = 12 g; 4 cL of aperitif, 42° \[42%\] whiskey = 17 g; 25 cL glass of 3° \[3%\] beer = 7.5 g; 25 cL glass of 6° \[6%\] beer = 15 g).
9. History of any clinically important drug allergy.
10. Had previously received BIA 9-1067.

    Prohibited treatments and dietary restrictions
11. Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or soda) in excess of 6 cups per day (or equivalent), of grapefruit, grapefruit-containing products, or alcoholic beverages within 24 hours before study Day 1.
12. Use of any over-the-counter drugs including herbal supplements (except for the occasional use of acetaminophen \[paracetamol\], aspirin and vitamins ≤100% recommended daily allowance) within 7 days before IMP administration.
13. Donation of blood (i.e. 450 ml) within 60 days before study Day 1.

    Young subjects only:

    Prohibited treatments and dietary restrictions
14. Prohibited Treatments: use of any investigational drug within 90 days (young and elderly subjects) or prescription drug within 30 days before investigational medical product (IMP) administration.

    Elderly subjects only:

    Prohibited treatments and dietary restrictions
15. For elderly subjects, previously prescribed medications that do not interfere with absorption, distribution, metabolism, and excretion or safety/tolerability evaluation of BIA 9-1067 and adrenal or renal function were allowed if the dose regimen had been stable for at least 4 weeks and was expected to remain stable throughout the study. Such concomitant medications was reviewed and mutually agreed upon by the sponsor and the investigator.

Primary outcomes:
measure: Cmax - Maximum Plasma Concentration
timeFrame: Day 1 and Day 7
measure: Tmax - Time to Reach Cmax
timeFrame: Day 1 and Day 7
measure: AUC0-t - Area Under the Plasma Concentration-time Curve From Time 0 to Last Observed Concentration
timeFrame: Day 1 and Day 7
Secondary outcomes:
Other outcomes:
Locations:
city: Rueil
country: France
facility: BIOTRIAL
state: Malmaison
Study officials:
affiliation: BIAL - Portela & Ca S.A.
name: Patrício SOARES-DA-SILVA, MD, PhD
role: STUDY_DIRECTOR
References: