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

NCT ID: NCT02191176

Last Updated: 2014-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30

Brief Summary

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

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Dextromethorphan syrup - low dose

Group Type: EXPERIMENTAL

Dextromethorphan syrup - low dose

Intervention Type: DRUG

Dextromethorphan syrup - high dose

Group Type: EXPERIMENTAL

Dextromethorphan syrup - high dose

Intervention Type: DRUG

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Dextromethorphan syrup - low dose

Intervention Type: DRUG

Dextromethorphan syrup - high dose

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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)

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

1134.3

Identifier Type: -

Identifier Source: org_study_id