Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ESR 1150 CL in Healthy Subjects

Study Overview
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Brief Summary
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The objective of this study was to obtain safety and tolerability data and first pharmacokinetic and pharmacodynamic data of escalating doses of ESR 1150 CL.

Official Title
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Administration of ESR 1150 CL in Ascending Doses of 0.5, 1, 2, 4 and 8 mg in an Open, Group Comparison and Placebo-controlled Design (Placebo Randomised Double Blind in the Dose Groups) for the Assessment of Safety, Tolerability (Maximum Tolerated Dose, MTD), Pharmacokinetics and Pharmacodynamics in 5 Groups of 8 Female and 5 Male Healthy Subjects, and 4 mg Additionally in Fed State, in a Cross Over Design. Safety, Tolerability and Pharmacokinetics of MTD/4, MTD/2 and MTD in 6 Healthy Male Subjects, Identified as CYP2D6 and/or Spartein Poor Metabolizers, in a 3-fold Cross Over, Open Study.

Conditions
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Healthy

Intervention / Treatment
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* Drug: ESR 1150 CL
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female Caucasian subjects as determined by results of screening Written informed consent in accordance with Good Clinical Practice and local legislation given Age ≥ 18 and ≤ 50 years Broca ≥ - 20 % and ≤ + 20 % for first part of study: extensive metabolizers of CYP2D6 and/or spartein type; for second part of study: poor metabolizers of CYP2D6 and/or spartein Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders of 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) (≤ 1 month prior to administration or during the trial, except for oral contraceptives) Use of any drugs which might influence the results of the trial (≤ 10 days prior to administration or during the trial except for oral contraceptives) Participation in another trial with an investigational drug (≤ 2 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/days) Drug abuse Blood donation > 100 ml (≤ 4 weeks prior to administration or during the trial) Excessive physical activities (≤ 10 days prior to administration or during the trial) Any laboratory value outside the reference range of clinical relevance Females only: No reliable contraception (examples of reliable contraception: oral contraceptives, 3-month injection, intrauterine device, sterilisation, condoms + spermicide) pregnancy or breast feeding period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ESR 1150 CL dose escalation fasted<br> | Drug: ESR 1150 CL<br> <br> |
| Experimental: ESR 1150 CL fed<br> | Drug: ESR 1150 CL<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 adverse events |  | up to 30 days | 
| Area under the curve (AUC) |  | up to 24 hours after administration | 
| Maximum concentration (Cmax) |  | up to 24 hours after administration | 
| Time to maximum concentration (tmax) |  | up to 24 hours after administration | 
| Apparent total plasma clearance (CLtot/f) |  | up to 24 hours after administration | 
| Apparent volume of distribution (Vz/f) |  | up to 24 hours after administration | 
| Elimination half-life (t1/2) |  | up to 24 hours after administration | 
| Amount excreted in urine (Ae) |  | up to 24 hours after administration | 
| Maximum flow rate (Qmax) | assessed by free uroflowmetry | up to 8 hours after administration | 
| Average flow rate (Qave) | assessed by free uroflowmetry | up to 8 hours after administration | 
| Voided volume (Vcomp) | assessed by free uroflowmetry | up to 8 hours after administration | 
| Voiding time (T100) | assessed by free uroflowmetry | up to 8 hours after administration | 
| Time to maximum flow (TQmax) | assessed by free uroflowmetry | up to 8 hours after administration | 
| Residual urinary volume | assessed by means of transabdominal ultrasound evaluation | up to 8 hours after administration | 
| Assessment of micturition pattern | evaluated by Independent reviewer | up to 8 hours after administration | 
| Amount of inhibition constants (Ki) at α1A, adrenoreceptor subtype level | assessed by ex vivo radioreceptor assay | up to 8 hours after administration |