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

Phase 1

Terminated

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: ESR 1150 CL

• Registration Number: NCT02209688
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2000-02
• Primary Completion: 2000-03
• Status Verified: 2014-08
• Study First Submitted: 2014-08-05
• Study First Submitted QC: 2014-08-05
• Last Update Submitted: 2014-08-05
• Study First Posted: 2014-08-06
• Last Update Posted: 2014-08-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 39

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
ESR 1150 CL dose escalation fasted	ESR 1150 CL	-
ESR 1150 CL fed	ESR 1150 CL	-

Primary Outcome Measures

Name	Time	Method
Maximum flow rate (Qmax)	up to 8 hours after administration	assessed by free uroflowmetry
Number of patients with adverse events	up to 30 days
Average flow rate (Qave)	up to 8 hours after administration	assessed by free uroflowmetry
Voided volume (Vcomp)	up to 8 hours after administration	assessed by free uroflowmetry
Voiding time (T100)	up to 8 hours after administration	assessed by free uroflowmetry
Time to maximum flow (TQmax)	up to 8 hours after administration	assessed by free uroflowmetry
Residual urinary volume	up to 8 hours after administration	assessed by means of transabdominal ultrasound evaluation
Assessment of micturition pattern	up to 8 hours after administration	evaluated by Independent reviewer
Amount of inhibition constants (Ki) at α1A, adrenoreceptor subtype level	up to 8 hours after administration	assessed by ex vivo radioreceptor assay
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