Clinical trial NCT02209688: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ESR 1150 CL in Healthy Subjects
Official title: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-06
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: up to 30 days
measure: Area under the curve (AUC)
timeFrame: up to 24 hours after administration
measure: Maximum concentration (Cmax)
timeFrame: up to 24 hours after administration
measure: Time to maximum concentration (tmax)
timeFrame: up to 24 hours after administration
measure: Apparent total plasma clearance (CLtot/f)
timeFrame: up to 24 hours after administration
measure: Apparent volume of distribution (Vz/f)
timeFrame: up to 24 hours after administration
measure: Elimination half-life (t1/2)
timeFrame: up to 24 hours after administration
measure: Amount excreted in urine (Ae)
timeFrame: up to 24 hours after administration
measure: Maximum flow rate (Qmax)
timeFrame: up to 8 hours after administration
measure: Average flow rate (Qave)
timeFrame: up to 8 hours after administration
measure: Voided volume (Vcomp)
timeFrame: up to 8 hours after administration
measure: Voiding time (T100)
timeFrame: up to 8 hours after administration
measure: Time to maximum flow (TQmax)
timeFrame: up to 8 hours after administration
measure: Residual urinary volume
timeFrame: up to 8 hours after administration
measure: Assessment of micturition pattern
timeFrame: up to 8 hours after administration
measure: Amount of inhibition constants (Ki) at α1A, adrenoreceptor subtype level
timeFrame: up to 8 hours after administration
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: