Evaluation of Pharmacokinetics, Safety and Tolerability of Single and Multiple Oral Doses of Neramexane Mesylate in Healthy Japanese Subjects

NCT00983099 | Completed Phase 1

• 1 other identifier: MRZ 92579/NA/1006
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Part 1 (single dose) Primary parameters

• Area under the plasma concentration curve from zero to infinity \[AUC0-inf\] and observed maximum plasma concentration \[Cmax\] of Japanese and Caucasian subjects for each dose group
• If at least 20% of the Japanese or of the Caucasian subjects have an area under the plasma concentration curve extrapolation \[AUCextrap%\] \>20% relative to AUC0-inf for one of the dose groups area under the plasma concentration curve from zero to the last measurable concentration \[AUC0- tz\] becomes primary parameter for Japanese and Caucasian subjects for all of the dose groups. In this case AUC0-tau will become a secondary parameter Secondary parameters and derived values from statistical analysis
• Dose proportionality and linearity in Japanese subjects
• Ratios (Japanese vs. Caucasian subjects) of AUC0-∞ and Cmax for each dose group
• Dose normalized AUC \[AUC0-inf,norm\], dose normalized Cmax \[Cmax,norm\], AUC0- tz, time of occurrence of Cmax \[tmax\], apparent terminal half life \[t½\], mean residence time \[MRT\], apparent (oral) total plasma clearance \[CLtot/f\], apparent volume of distribution during the terminal disposition phase \[Vz/f\], AUCextrap%, apparent terminal disposition rate constant \[λz\], weight corrected AUC0-inf, weight corrected AUC0-tz, weight corrected Cmax, weight corrected CLtot/f, cumulative amount of excreted Neramexane into urine \[Ae0-tz\], fraction of orally administrated drug excreted into urine \[fe/f\], renal clearance \[CLR\] and apparent non-renal clearance \[CLNR/f\]
• Safety and tolerability Other parameters
• Pharmacogenetics
• Amount of N-OH Neramexane excreted in urine \[Ae0-tz\] if a validated method will be available at the time of analysis
• Metabolite determination (N-OH Neramexane) in plasma and urine, optional (may be analyzed and evaluated if a validated method will be available at the time of analysis)
• Endogenous creatinine clearance \[CLCR\], amount of excreted creatinine into urine per hour \[AeCR,hr\]
• Evaluation of further metabolites will be described in detail in the Statistical Analysis Plan

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Determination of plasma concentration after single and multiple dose

  1 year

Interventions

Neramexane DRUG

single and multiple dose, tablets, oral

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects
• Caucasian (Part 1 only) or Japanese origin
• Japanese subjects must have a Japanese passport, Japanese grandparents and parents and not have lived outside of Japan for more than 5 years
• Aged 20 to 55 years (inclusive)
• Body weight between 50 and 90 kg (inclusive) with BMI ranging from 18.0 to 28.0 kg/m2 (inclusive) Japanese females may have a body weight of at least 45 kg (inclusive) with BMI ranging from 17.0 to 28.0 kg/m2 (inclusive)
• Females must have a negative urine pregnancy test at screening and on Day -1 for Part 1 and on Day 1 for Part 2
• Subjects must be willing to use one of the following methods of contraception from the first dose of trial medication until completion of follow-up procedures.
• All subjects must agree to use condom and spermicide.
• Male subjects without vasectomy (with documentation of azoospermia) must assure that their female partners uses another form of contraception such as non hormonal IUD, diaphragm.
• Female subjects of childbearing potential must agree to use an effective method of birth control such as sexual abstinence, vasectomised partner, non hormonal IUDs or double contraception methods (e.g., condom with spermicide cream) from Screening until one month after last application of study drug.
• Willing and able to give written informed consent after having been informed of the requirements and the restrictions of the study

You may not qualify if:

• Subjects who have taken part in the drug administration phase of the single dose part are excluded from participation in the multiple dose part of the study and vice versa
• Any clinically relevant finding on medical history or, physical examination affecting subject's safety or the study objectives
• Any disease or condition, which could influence the physiological absorption, distribution and metabolic turnover (e.g. endocrine diseases, febrile conditions, severe infections, acute inflammations, chronic diarrhoea, chronic vomiting, gastrointestinal disease or surgery of the gastrointestinal tract, including cholecystectomy); appendectomy older than 6 months is allowed
• Prior history or present evidence of clinically significant metabolic, renal, hepatic, pulmonary or cardiovascular disease, CNS disorders or disturbances of bleeding (hemorrhagic diathesis), diagnosis of malignancy, polyneuropathy or psychiatric disorder, organ transplantation
• Any clinically relevant abnormal laboratory value (haematology, clinical chemistry, urinalysis) or laboratory values which in the discretion of the investigator and the Merz scientific expert might affect subject's safety or the study objectives
• Positive serology for human immunodeficiency virus \[HIV\] (HIV1/HIV2 antibodies), hepatitis B surface antigen \[HBsAg\], antibodies against hepatitis C virus \[anti-HCV\]
• Clinically relevant abnormalities in the 12-lead ECG which in the discretion of the investigator and the Merz scientific expert might affect the study objectives
• Presence or history of clinically relevant allergy or a known or suspected hypersensitivity to Neramexane, Memantine or Amantadine and/or its study medication excipients and to quinine hydrochloride (slight seasonal hay fever is allowed as long as the season does not meet the study period)
• History of alcohol or drug dependence
• Alcohol consumption averaging more than 40 g alcohol (4 units) daily (28 units per week) within the last year for males and more than 20 g (2 units) daily within the last year for females
• Regular caffeine consumption averaging more than 5 cups of coffee or equivalent (500mg caffeine) per day within the last year
• Smoking more than 5 cigarettes per day or equivalent (use of snuff, nicotine replacement chewing tobacco)
• Refusal or inability to eat the meals provided by the clinic (e.g. vegetarian)
• Nursing mother
• Woman planning pregnancy during the course of the trial

Sponsors & Collaborators

• Merz Pharmaceuticals GmbH: lead

Study Sites (1)

California Clinical Trials

Glendale, California, 91206, United States

Location

MeSH Terms

Interventions

neramexane

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 18, 2009
• First Posted: September 23, 2009
• Study Start: September 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: April 15, 2011

Record last verified: 2011-04

Locations

US (1)