Dose Tolerance Study in Healthy Male Volunteers After Intranasal Application of Epinastine Nasal

Study Overview
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Brief Summary
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Safety, tolerability and pharmacokinetics

Official Title
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A Double-blind, Randomised, Placebo-controlled Single Increasing Dose Tolerance Study in Healthy Male Volunteers After Intranasal Application of Epinastine Nasal (Dosage: 0.035 mg (0.025 % Solution) - 0.42 mg (0.3 % Solution))

Conditions
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Healthy

Intervention / Treatment
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* Drug: Epinastine nasal
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants in the study should be healthy, range from 21 to 50 years of age and be within ± 20 % of their normal weight (Broca -Index) Subsequently each subject will have his medical history taken and will receive a complete medical examination (incl. blood pressure and pulse rate measurements) as well as a 12-lead ECG. Haematological, hepatic and renal function tests will be carried out in the laboratory (Bioscientia Ingelheim, Germany). The subjects will fast for 12 hours before collection of specimens for all laboratory evaluations. The above mentioned examinations will be performed within 14 days before the first administration of the test substance In accordance with good clinical practice (GCP) and the local legislation all volunteers will have given their written informed consent prior to admission to the study Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastro-intestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study Use of any drugs which might influence the results of the trial (≤ one week prior to administration or during the trial) Participation in another trial with an investigational drug (≤ two months prior to 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 (> 60 g/day) Drug abuse Blood donation (≥ 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within the last week before the study) Any laboratory value outside the reference range of clinical relevance

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epinastine nasal<br>single rising doses | Drug: Epinastine nasal<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with clinically relevant findings in vital signs | blood pressure, pulse rate | up to 8 days after drug administration | 
| Number of patients with clinically relevant findings in 12-lead ECG |  | up to 8 days after drug administration | 
| Number of patients with adverse events |  | up to 8 days after drug administration | 
| Number of patients with clinically relevant findings in laboratory parameters |  | up to 8 days after drug administration | 
| Changes in rhinoscopy assessment |  | up to 8 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured concentration in plasma (Cmax) |  | up to 48 hours after drug administration | 
| Time from dosing to the maximum concentration in plasma (tmax) |  | up to 48 hours drug administration | 
| Area under the concentration-time curve in plasma (AUC) |  | up to 48 hours after drug administration | 
| Terminal rate constant of in plasma (λz) |  | up to 48 hours after drug administration | 
| Apparent terminal half-life in plasma (t1/2) |  | up to 48 hours after drug administration | 
| Total mean residence time in the body (MRTtot) |  | up to 48 hours after drug administration | 
| Total clearance in plasma after extravascular administration (CL/F) |  | up to 48 hours after drug administration | 
| Apparent volume of distribution during the terminal phase (Vz/F) |  | up to 48 hours after drug administration | 
| Amount excreted into urine (Ae) |  | up to 48 hours after drug administration | 
| Renal clearance (CLR) |  | up to 48 hours after drug administration | 
| Assessment of dose-proportionality of epinastine nasal | based on AUC and Cmax | up to 48 hours after drug administration |