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Fasting Bioequivalence Study of Memantinol 20 mg Tablets Versus Akatinol Memantine® 20 mg Tablets In Normal Healthy Subjects

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ClinicalTrials.gov Identifier: NCT03121820
Recruitment Status : Completed
First Posted : April 20, 2017
Results First Posted : October 29, 2018
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Geropharm

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Bioequivalence, AUC, Cmax, Pharmacokinetics
Interventions Drug: Memantinol tablets, 20 mg
Drug: Akatinol Memantine® tablets, 20 mg
Enrollment 18
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).
Arm/Group Title Memantinol First, Then Akatinol Memantine® Akatinol Memantine® First, Then Memantinol
Hide Arm/Group Description

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

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

Period Title: First Period
Started 9 9
Completed 9 9
Not Completed 0 0
Period Title: Second Period (After Washout)
Started 9 9
Completed 9 9
Not Completed 0 0
Arm/Group Title Memantinol First, Then Akatinol Memantine® Akatinol Memantine® First, Then Memantinol Total
Hide Arm/Group Description

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

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

Total of all reporting groups
Overall Number of Baseline Participants 9 9 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
9
 100.0%
9
 100.0%
18
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 18 participants
Female
5
  55.6%
4
  44.4%
9
  50.0%
Male
4
  44.4%
5
  55.6%
9
  50.0%
1.Primary Outcome
Title Pharmacokinetics of Memantinol by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Memantinol Tablets, 20 mg Akatinol Memantine® Tablets, 20 mg
Hide Arm/Group Description:

Treatment A: a single oral dose of memantin 20 mg film-coated tablet (JSC "GEROPHARM", Russia - test)

Memantinol tablets, 20 mg: Bioequivalence Memantine Hydrochloride (JSC "GEROPHARM", Russia) 20 mg film-coated tablets fasting condition

Treatment B: a single oral dose of memantin 20 mg film-coated tablet (Merz Pharma GmbH & Co. KGaA, Germany - reference)

Akatinol Memantine® tablets, 20 mg: Bioequivalence Memantine Hydrochloride (Merz Pharma GmbH & Co. KGaA, Germany) 20 mg film-coated tablets fasting condition

Overall Number of Participants Analyzed 18 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
1920.362
(449.289%)
2096.669
(537.147%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Memantinol Tablets, 20 mg, Akatinol Memantine® Tablets, 20 mg
Comments Memantinol 20 mg Tablets Versus Akatinol Memantine® 20 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric mean ratios were fully contained within the predefined equivalence limits of 80.00 % to 125.00 %
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Test/Ref Geometric mean ratio x 100
Comments Bioequivalence is established when 90% Confidence Interval falls within 80.00 % -125.00 %.
Method of Estimation Estimation Parameter Test/Ref Geometric mean ratio x 100
Estimated Value 93.8
Confidence Interval (2-Sided) 90%
88.25 to 99.77
Estimation Comments [Not Specified]
2.Primary Outcome
Title Pharmacokinetics of Memantinol by Assessment of Observed Maximum Plasma Concentration (Cmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Memantinol Tablets, 20 mg Akatinol Memantine® Tablets, 20 mg
Hide Arm/Group Description:

Treatment A: a single oral dose of memantin 20 mg film-coated tablet (JSC "GEROPHARM", Russia - test)

Memantinol tablets, 20 mg: Bioequivalence Memantine Hydrochloride (JSC "GEROPHARM", Russia) 20 mg film-coated tablets fasting condition

Treatment B: a single oral dose of memantin 20 mg film-coated tablet (Merz Pharma GmbH & Co. KGaA, Germany - reference)

Akatinol Memantine® tablets, 20 mg: Bioequivalence Memantine Hydrochloride (Merz Pharma GmbH & Co. KGaA, Germany) 20 mg film-coated tablets fasting condition

Overall Number of Participants Analyzed 18 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
34.617
(8.302%)
37.578
(8.858%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Memantinol Tablets, 20 mg, Akatinol Memantine® Tablets, 20 mg
Comments Memantinol 20 mg Tablets Versus Akatinol Memantine® 20 mg
Type of Statistical Test Non-Inferiority or Equivalence
Comments The analysis was conducted using an analysis of variance (ANOVA) including fixed effects for treatment, sequence, period and subject within sequence. All pharmacokinetic parameters were log-transformed prior to analysis. Bioequivalence was concluded, when the 90% confidence interval (CI) for the geometric mean ratios were fully contained within the predefined equivalence limits of 80.00 % to 125.00 %
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Test/Ref Geometric mean ratio x 100
Comments Bioequivalence is established when 90% Confidence Interval falls within 80.00 % -125.00 %.
Method of Estimation Estimation Parameter Test/Ref Geometric mean ratio x 100
Estimated Value 92.3
Confidence Interval (2-Sided) 90%
86.37 to 98.55
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Memantinol Tablets, 20 mg Akatinol Memantine® Tablets, 20 mg
Hide Arm/Group Description

Active experimental drug

Memantinol: Single orally administered dose of Memantinol (20 mg memantine) in a fasting state

Active comparator

Akatinol Memantine®: Single orally administered dose of Akatinol Memantine® (20 mg memantine) in a fasting state

All-Cause Mortality
Memantinol Tablets, 20 mg Akatinol Memantine® Tablets, 20 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Memantinol Tablets, 20 mg Akatinol Memantine® Tablets, 20 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)   0/18 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Memantinol Tablets, 20 mg Akatinol Memantine® Tablets, 20 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   2/18 (11.11%)   2/18 (11.11%) 
Nervous system disorders     
Dizziness * [1]  2/18 (11.11%)  2/18 (11.11%) 
*
Indicates events were collected by non-systematic assessment
[1]
The volunteers during period, 2.5 hours after taking the test drug (20 mg orally) was dizzy. Deviations in any Analyzed indicators were not revealed. There was no volunteer Action taken. AE resolved full recovery.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from GEROPHARM will be obtained and a draft manuscript will be submitted to GEROPHARM for scrutiny and comment. The choice of conduit will be mutually agreed on by the Principal Investigator and GEROPHARM.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GEROPHARM Clinical Leader
Organization: GEROPHARM
Phone: +7(812) 703-79-75
EMail: inform@geropharm.ru
Layout table for additonal information
Responsible Party: Geropharm
ClinicalTrials.gov Identifier: NCT03121820     History of Changes
Other Study ID Numbers: BIOMEM-20
First Submitted: April 18, 2017
First Posted: April 20, 2017
Results First Submitted: July 20, 2017
Results First Posted: October 29, 2018
Last Update Posted: October 29, 2018