Not applicable
Conditions
Interventions
Group 1: TEST treatment: administration of a single oral dose of "InfectoDex" 5.0 ml (containing approx. 2 mg of dexamethasone)
Group 2: REFERENCE treatment: administration of a single oral dose of 1
Sponsors
InfectoPharm Arzneimittel und Consilium GmbH
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: • caucasian • male / female • age: 18-55 years • body weight of 60 kg or higher, Body Mass Index 19 – 27 kg/m2 • considered to be healthy on the basis of extensive pre-study screening • willing and capable to confirm written consent to enrolment after ample information has been provided
Exclusion criteria
Exclusion criteria: • subjects with any skin abnormality and / or neurodermatitis and / or chronic skin disease • subjects with a history of any severe gastrointestinal disease with potential sequelae, esp. ulcer, haemorrhage, diverticulitis, ulcerative colitis • subjects with corneal damage / ulcer • subjects with glaucoma • subjects with osteoporosis • subjects with poliomyelitis • subjects who had been vaccinated or planned to be vaccinated with a live virus vaccination (8 weeks before until 2 weeks after administration of study drugs) • subjects with history of psychiatric diseases • subjects with history of epilepsy • subject with history of pancreatitis • subjects with history of cerebrovascular events • subjects with history of pulmonary embolism • subjects with history of venous thromboembolic events • subjects with history of hypertension • subjects with any relevant clinical abnormality (as based on extensive medical history, physical examination, vital signs and 12-lead ECG); • subjects with bronchial asthma, COPD, or actual obstructive bronchitis; • subjects with hypothyroidism /hyperthyroidism; • subjects with chronic heart failure; • subjects with previous myocardial infarction; • subjects with liver disease; • subjects with cardiac arrhythmia; • subjects with diabetes mellitus; • subjects with any systemic or chronic infections (bacterial, viral, fungal, parasites); • subjects with history of latent infections, esp. tuberculosis • subjects with any acute infection or with actual therapy-requiring allergies (including drug allergies) within the last two weeks; • subjects with suspicion of hypersensitivity to dexamethasone or to any of the excipients of the study medications • subjects with any clinically relevant laboratory abnormality. Clinically relevant laboratory abnormality is formally defined as follows: ? Serology for hepatitis and HIV: any positive result in the initial examination which is confirmed by a second examination; ? Urine screen for substances of abuse: any positive result in the initial examination which is confirmed by a second examination; ? Urinalysis (Combur 9®): any more than borderline positive result in the initial examination which is confirmed by a second examination (no limitations apply for pH); ? Hematocrit, haemoglobin, MCV, MCH, MCHC, erythrocyte count (RBC), total leukocyte count, platelet count, prothrombin time (Quick), activated partial thromboplastin time (aPTT), SGOT (ASAT), SGPT (ALAT), potassium, sodium, chloride, creatinine, glucose: any value more than 10% outside the respective reference range in the initial examination which is confirmed by a second examination; ? Gamma-GT, alkaline phosphatase, lactic dehydrogenase (LDH), total protein, albumin, urea, uric acid, creatine kinase (CK): any value more than 20% outside the respective reference range in the initial examination which is confirmed by a second examination; ? total bilirubin, total cholesterol, triglycerides, differential leukocyte count: any value more than 50 % outside the respective reference range in the initial examination which is confirmed by a second examination. Exceptions are possible upon decision of the Principal Investigator (e.g. exclusion of a subject with a less than 10 % elevation above the reference range for Gamma-GT, SGOT and SGPT). • subjects receiving any medication within 2 weeks prior to study start or during the study (exceptions possible upon decision of Principal Investigator, e.g. paracetamol (acetaminophen)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main pharmacokinetic parameters of dexamethasone for the assessment of bioequivalence: AUC0-t, Cmax (for assessment of bioequivalence after blood sampling / concentration measurement in the 24 volunteers). Blood sampling for determination of dexamethasone concentrations in each period was carried out approx. 5 min prior to dosing and 0:15, 0:30, 0:45, 1, 1:15, 1:30, 1:45, 2, 2:30, 3, 4, 5, 6, 8, 12, 16 and 24 hours postdose (18 samples); for each sample, 9 ml were withdrawn. Plasma concentrations of dexamethasone were determined using a specific and sensitive HPLC method. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Additional pharmacokinetic parameters of dexamethasone: AUC0-8, tmax, MRT-8, t½ lambda z (apparent terminal elimination half-life). Blood sampling for determination of dexamethasone concentrations in each period was carried out approx. 5 min prior to dosing and 0:15, 0:30, 0:45, 1, 1:15, 1:30, 1:45, 2, 2:30, 3, 4, 5, 6, 8, 12, 16 and 24 hours postdose (18 samples); for each sample, 9 ml were withdrawn. Plasma concentrations of dexamethasone were determined using a specific and sensitive HPLC method. • pharmacodynamic parameters of dexamethasone: cortisol plasma concentrations, including predose/postdose changes of individual concentrations and of AUEC. Blood sampling for determination of endogenous cortisol concentrations in each period was carried out -24 h, -16 h, -8h, 0h, 8h, 16h and 24 h (relative to dosing; for each sample, 4.7 ml were withdrawn). For measurement of endogenous cortisol, a specific and validated clinical laboratory routine method (University Hospital Cologne, Germany) was used. • Safety and Tolerability: ? Medical history, adverse events and well-being ? Laboratory screen (haematology, clinical chemistry and urinalysis) ? Physical examination ? Vital functions: blood pressure, pulse rate, body temperature ? 12-lead ECG | — |
Countries
Germany
Contacts
Public ContactChristian Queckenberg
Uniklinik Köln, Institut für Pharmakologie
Outcome results
None listed