Evaluation of Dose-Dependent Repeated-Dose Neramexane Effects on Cardiac Repolarisation (QT/QTc Interval Duration): Electrocardiogram (ECG) Study in Healthy Adult Subjects

NCT00978614 | Completed Phase 1

• 1 other identifier: MRZ 92579/TI/1006
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

Primary:

• To assess the effects of ascending repeated-doses of oral \[p.o.\] neramexane at therapeutic and supra-therapeutic steady-state doses on cardiac repolarisation (QT/QTc interval) in healthy male and female subjects. Secondary:
• To assess the pharmacokinetics \[PK\] of neramexane and N-OH neramexane (if a validated method will be available for this metabolite) following repeated daily doses of 50 mg (steady state), 75 mg (steady state) and 87.5 mg (steady state).
• To assess the safety and tolerability of neramexane 50 mg, 62.5 mg, 75 mg and 87.5 mg repeated-dose treatments when gradually up-titrated in healthy subjects.
• To assess the concentration-QT relationship.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• To assess the effects of ascending repeated-doses of oral [p.o.] neramexane at therapeutic and supra-therapeutic steady-state doses on cardiac repolarisation (QT/QTc interval) in healthy male and female subjects.

  steady state, therapeutic dose

Study Arms (1)

Neramexane, Placebo, Moxifloxacin

EXPERIMENTAL

Drug: Neramexane

Interventions

Neramexane DRUG

Dosage form: 25 mg immediate release \[IR\] tablets (=15.9 mg neramexane free base) 37.5 mg IR tablets (=23.9 mg neramexane free base)

Neramexane, Placebo, Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult subject confirmed on the basis of extensive pre-study screening investigations
• Aged 18 to 45, inclusive
• Body mass index \[BMI\] of 18-28 kg/m² (inclusive) and a body weight of 50 -\<90 kg
• Willing and able to provide written informed consent after having been informed of the requirements and the restrictions of the study
• Female subject of child-bearing potential must agree to use a non-hormonal highly effective method of birth control defined as those which result in a low failure rate when used consistently and correctly, such as sexual abstinence, vasectomized partner, non-hormone releasing intrauterine devices \[IUDs\].
• A sexually active man, who has not been sterilized surgically, must agree to use together with his female partner a double contraception method during intercourse:
• IUD or hormonal contraception plus condom or diaphragm or spermicide, or
• condom plus diaphragm or observe abstinence during the entire clinical study until the Final Examination.

You may not qualify if:

• History of clinically relevant allergy or known hypersensitivity to neramexane/memantine/amantadine and their derivatives
• History of clinically relevant allergy or known hypersensitivity to moxifloxacin or any other quinolone antibiotics
• History of clinically relevant allergy or known hypersensitivity to any inactive ingredient in any of the used investigational products or positive control especially quinine
• Any contraindications which are indicated in the current SPC of Avalox®
• Evidence or (family) history of long QT syndrome
• Exposure to another investigational agent within the last two months before Day -1
• Lactating or pregnant female, or female planning to become pregnant during study conduct
• Any evidence of a significant cardiovascular, pulmonary, renal, hepatic, gastrointestinal, endocrinological, metabolic (acidosis), psychiatric, neurologic, relevant eye disorder or other diseases at screening
• ECG abnormalities of clinical relevance, in particular abnormal prolongations of QT/QTc-interval (i.e. QTc \>450 ms, PQ ≥220 ms)
• Systolic blood pressure \<95 mmHg or \>140 mmHg or diastolic blood pressure \<50 mmHg or \>95 mmHg in semi-supine position
• Pulse rate \<45 or \>100 beats per minute
• History of malignancy
• Any clinically relevant deviation in clinical or laboratory assessment
• Acute or chronic clinically relevant infections
• Current evidence of hypokalemia and/or hypomagnesemia (= below lower limit of laboratory normal range plus 0.3 mmol/L as safety margin)

Sponsors & Collaborators

• Merz Pharmaceuticals GmbH: lead

Study Sites (1)

Parexel International GmbH

Berlin, 14050, Germany

Location

MeSH Terms

Interventions

neramexane

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 10, 2009
• First Posted: September 17, 2009
• Study Start: September 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: February 15, 2011

Record last verified: 2011-02

Locations

DE (1)