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

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.

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.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: ESR 1150 CL

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: ESR 1150 CL dose escalation fasted	Drug: ESR 1150 CL
Experimental: ESR 1150 CL fed	Drug: ESR 1150 CL

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2000
• Primary Completion (Actual): March 1, 2000

Study Registration Dates

• First Submitted: August 5, 2014
• First Submitted That Met QC Criteria: August 5, 2014
• First Posted (Estimate): August 6, 2014

Study Record Updates

• Last Update Posted (Estimate): August 6, 2014
• Last Update Submitted That Met QC Criteria: August 5, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 1172.2