Study to Investigate Safety With Special Emphasis on ECG Effects and Tolerability After Oral Doses of Dextromethorphan Hydrobromide Monohydrate in Healthy Male and Female Subjects

Boehringer Ingelheim

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Dextromethorphan syrup - high dose

Drug: Placebo

Drug: Dextromethorphan syrup - low dose

Study type

Interventional

Funder types

Industry

Identifiers

NCT02191176

1134.3

Details and patient eligibility

About

The primary objective of the current study is to investigate the safety with special emphasis on ECG effects, and tolerability of dextromethorphan hydrobromide monohydrate (2mg/mL syrup) in healthy male and female subjects following oral administration of 30 mg q.i.d. and 90 mg q.i.d. for 2 days followed by a single morning dose (extensive metabolisers of CYP 2D6) and for 10 days followed by a single morning dose (poor metabolisers of CYP 2D6).

Additionally pharmacokinetic properties of dextromethorphan and its main metabolites dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan will be investigated

Enrollment

48 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, oral body temperature, vital signs (blood pressure, pulse rate), 12-lead Electrocardiogram (ECG), clinical laboratory tests
Age ≥18 and Age ≤55 years
BMI ≥18.5 and BMI ≤30 kg/m2 (Body Mass Index)
Extensive or poor metabolisers for CYP 2D6 based on the results of a genotyping test
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion criteria

Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
Any evidence of a clinically relevant concomitant disease
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Surgery of the gastrointestinal tract (except appendectomy)
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
History of relevant orthostatic hypotension, fainting spells or blackouts
Chronic or relevant acute infections
History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
Participation in another trial with an investigational drug within one month prior to first administration or during the trial
Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
Inability to refrain from smoking on trial days
Alcohol abuse (more than 60 g/day)
Drug abuse
Blood donation (more than 100 mL within four weeks prior to first administration or during the trial)
Excessive physical activities (within one week prior to first administration or during the trial)
Any laboratory value outside the reference range that is of clinical relevance
Inability to comply with dietary regimen of trial site
A marked baseline prolongation of QTc interval of >450 ms;
A history of additional risk factors for Torsades de points (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

Exclusion criteria specific for this study:

Use of drugs that inhibit or induce cytochrome P 450 enzymes, especially CYP2D6, within 30 days prior to first administration of the study medication or during the trial

For female subjects:

Pregnancy or planning to become pregnant within 2 months of study completion
Positive pregnancy test
No adequate contraception in woman of child bearing potential during the study, i.e., sterilisation, intrauterine device, injectables, oral contraceptive combined with a barrier method of contraception
Lactation period