Bioequivalence, AUC, Cmax, Pharmacokinetics
Conditions
Brief summary
This study are two-way crossover, open-label, single-dose, fasting, bioequivalence study of Memantinol® (JSC GEROPHARM, Russia) 20 mg tablets versus Akatinol Memantine® (Merz Pharma GmbH & Co. KGaA, Germany) 20 mg tablets in normal healthy subjects
Detailed description
Study to evaluate the bioequivalence of orally administered memantinol preparations, film-coated tablets, 20 mg
Interventions
DRUGMemantinol tablets, 20 mg
Bioequivalence Memantine Hydrochloride (JSC GEROPHARM, Russia) 20 mg film-coated tablets fasting condition
DRUGAkatinol Memantine® tablets, 20 mg
Bioequivalence Memantine Hydrochloride (Merz Pharma GmbH & Co. KGaA, Germany) 20 mg film-coated tablets fasting condition
Sponsors
Geropharm
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
Open Label
Intervention model description
two-way crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent form. * Healthy male and female subjects aged 18 to 45 years. * Verified diagnosis is healthy according to data Standard clinical, laboratory and Instrumental methods of examination. * Have a body mass index between 18,5 and 27 kg/m2. * Females must have a negative pregnancy test. * Subjects must use, with their partner, methods of highly effective contraception; if the Hormonal contraceptives was used they must canceled have at least 2 month before the study. from the time of IMP administration until 3 months after the last dose of IMP.
Exclusion criteria
* History of serious allergic problems/events * Medicinal intolerance. * History of allergic reactions to memantine or investigator's product components * Any acute and chronic diseases of the cardiovascular system, cardiovascular, bronchopulmonary, neuroendocrinal systems, as well as diseases of the gastrointestinal tract, liver, kidneys, blood. * Acute infectious diseases in less than 4 weeks before the start of the study. * Subjects who have taken medication 4 weeks preceding before the study. * Subjects who have taken any drugs known effects on hemodynamics or to induce or inhibit hepatic drug metabolism within 30 days prior to administration of the study medication (examples of inducers: barbiturates, omeprazole, etc.). * Donation of plasma (450 mL or more) within 2 month prior to administration of the study medication. * History of significant alcohol or drugs abuse or any indication of the regular use of more than 10 units of alcohol per week (1 Unit = 200 mL of wine or 500 mL of beer or 50 mL of alcohol 40%). * Smokers. * Participation in other clinical training is less than than for 3 months before the study. * Lack of signed informed consent form. * ECG or vital signs abnormalities (clinically significant). * Positive testing for alcohol, drugs, pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of Memantinol by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf)) | 0 hours (pre-dose), as well as at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose | Comparison of the pharmacokinetic profile in terms of plasma concentration-time curve from time zero extrapolated to infinity, AUC(0-inf), of memantinol sourced in Memantinol® (JSC GEROPHARM, Russia) and Akatinol Memantine® (Merz Pharma GmbH & Co. KGaA, Germany) |
| Pharmacokinetics of Memantinol by Assessment of Observed Maximum Plasma Concentration (Cmax) | 0 hours (pre-dose), as well as at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose | Comparison of the pharmacokinetic profile in terms of observed maximum plasma concentration, taken directly from the individual concentration-time curve, Cmax, of memantinol sourced in Memantinol® (JSC GEROPHARM, Russia) and Akatinol Memantine® (Merz Pharma GmbH & Co. KGaA, Germany) |
Countries
Russia
Participant flow
Recruitment details
Participants recruited at GKB № 15 im. O. M. Filatova Public Healthcare Institution of Department of health care of Moscow, Russian Federation between October and November 2016
Pre-assignment details
18 participants recruited; 25 screened, 7 excluded (5 did not meet inclusion criteria and 2 refused participation).
Participants by arm
| Arm | Count |
|---|---|
| Memantinol First, Then Akatinol Memantine® First Intervention Period (3 day):
Memantinol tablet: Single administered dose of Memantinol ( 20 mg memantin) in a fasting state
(21 day washout period)
Second Intervention Period (3 day):
Akatinol Memantine® tablet: Single administered dose of Memantinol ( 20 mg memantin) in a fasting state | 9 |
| Akatinol Memantine® First, Then Memantinol First Intervention Period (3 day):
Akatinol Memantine® tablet: Single administered dose of Memantinol ( 20 mg memantin) in a fasting state
(21 day washout period)
Second Intervention Period (3 day):
Memantinol tablet: Single administered dose of Memantinol ( 20 mg memantin) in a fasting state | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Memantinol First, Then Akatinol Memantine® | Akatinol Memantine® First, Then Memantinol | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 18 | 2 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Pharmacokinetics of Memantinol by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))
Comparison of the pharmacokinetic profile in terms of plasma concentration-time curve from time zero extrapolated to infinity, AUC(0-inf), of memantinol sourced in Memantinol® (JSC GEROPHARM, Russia) and Akatinol Memantine® (Merz Pharma GmbH & Co. KGaA, Germany)
Time frame: 0 hours (pre-dose), as well as at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Memantinol Tablets, 20 mg | Pharmacokinetics of Memantinol by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf)) | 1920.362 ng*h/mL | Geometric Coefficient of Variation 449.289 |
| Akatinol Memantine® Tablets, 20 mg | Pharmacokinetics of Memantinol by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf)) | 2096.669 ng*h/mL | Geometric Coefficient of Variation 537.147 |
Comparison: Memantinol 20 mg Tablets Versus Akatinol Memantine® 20 mgp-value: 0.0590% CI: [88.25, 99.77]Test/Ref Geometric mean ratio x 100
Primary
Pharmacokinetics of Memantinol by Assessment of Observed Maximum Plasma Concentration (Cmax)
Comparison of the pharmacokinetic profile in terms of observed maximum plasma concentration, taken directly from the individual concentration-time curve, Cmax, of memantinol sourced in Memantinol® (JSC GEROPHARM, Russia) and Akatinol Memantine® (Merz Pharma GmbH & Co. KGaA, Germany)
Time frame: 0 hours (pre-dose), as well as at 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Memantinol Tablets, 20 mg | Pharmacokinetics of Memantinol by Assessment of Observed Maximum Plasma Concentration (Cmax) | 34.617 ng/mL | Geometric Coefficient of Variation 8.302 |
| Akatinol Memantine® Tablets, 20 mg | Pharmacokinetics of Memantinol by Assessment of Observed Maximum Plasma Concentration (Cmax) | 37.578 ng/mL | Geometric Coefficient of Variation 8.858 |
Comparison: Memantinol 20 mg Tablets Versus Akatinol Memantine® 20 mgp-value: 0.0590% CI: [86.37, 98.55]Test/Ref Geometric mean ratio x 100