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

NCT02191176 | Completed Phase 1

• 1 other identifier: 1134.3
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (6)

• Number of patients with abnormal findings in physical examination

  up to day 20

• Number of patients with clinically significant changes in vital signs (blood pressure and pulse rate)

  up to day 20

• Number of patients with clinically significant changes in 12-lead ECG (electrocardiogram) including QT interval and heart rate corrected QTcN, QTcF (Fridericia) and QTcB (Bazett)

  up to day 20

• Number of patients with abnormal changes in laboratory parameters

  up to day 20

• Assessment of tolerability by investigator on a 4-point scale

  day 20 (end of trial examination)

• Number of patients with adverse events

  up to 48 days

Secondary Outcomes (13)

• Cmax (maximum measured concentration of the analyte in plasma) after the first dose

  within 5 hours after first drug administration

• tmax (time from dosing to the maximum concentration of the analyte in plasma) after the first dose

  within 5 hours after first drug administration

• AUCt1-t2 (area under the concentration-time curve of the analyte in plasma from the time interval t1 to t2) after the first dose

  within 5 hours after first drug administration

• AUC0-5 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 5 hours after administration) after the first dose

  within 5 hours after first drug administration

• Cmax,N (maximum measured concentration of the analyte in plasma following the Nth dose) after the last dose

  up to day 13

Study Arms (3)

Dextromethorphan syrup - low dose

EXPERIMENTAL

Drug: Dextromethorphan syrup - low dose

Dextromethorphan syrup - high dose

EXPERIMENTAL

Drug: Dextromethorphan syrup - high dose

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Dextromethorphan syrup - low dose DRUG

Dextromethorphan syrup - low dose

Dextromethorphan syrup - high dose DRUG

Dextromethorphan syrup - high dose

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2014
• First Posted: July 16, 2014
• Study Start: June 1, 2009
• Primary Completion: July 1, 2009
• Last Updated: July 16, 2014

Record last verified: 2014-07