acute respiratory insufficiency, including such conditions as opioid and anesthetic-induced respiratory depression, post-anesthetic atelectasis, and central apneas (e.g., apnea of prematurity). MedDRA version: 14.1 Level: SOC Classification code 10038738 Term: Respiratory, thoracic and mediastinal disorders System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Doxapram
Product Name: Dopram
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DOXAPRAM
CAS Number: 309-29-5
Concentration unit: mg milligram(s)
Concentration type: up to
Co
Sponsors
Leids Universitair Medisch Centrum (LUMC)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1.Subjects must be willing to give written informed consent for the trial and able to ad-here to dose and visit schedules. 2.The subject is male >18 to =45 years of age. 3.Subjects must have Body Mass Index [weight/height2 (kg/m2)] between 18 – 30 kg/m2 (Parts 1 and 2). 4.Have no clinical or electrocardiographic signs of ischemic heart disease as deter-mined by the Investigator with normal cardiac intervals appropriate for their gender. The Screening 12 lead ECG conduction intervals must be within gender specific normal range (e.g., QTcB males ? 500 msec, PR interval ? 200 msec). 5.Subjects’ clinical laboratory tests (CBC, blood chemistry, and urinalysis) must be within normal limits or clinically acceptable to the investigator and within an allowed expanded range (Appendix 2). 6.Vital sign measurements (taken after ~3 minutes in a sitting position) must be within the following ranges: (Individuals with values outside (or indicate lower or higher) of these ranges may be enrolled if clinically acceptable to the investigator and indepen-dent physician) a. oral body temperature, between 35.0?C and 37.5?C b. systolic blood pressure, 80 to 140 mm Hg c. diastolic blood pressure, 40 to 90 mm Hg d.pulse rate, 40 to 100 bpm 7.Subjects must be free of any clinically significant disease that would interfere with the study evaluations Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Past history of the anxiety disorder including panic attack, obsessive compulsive dis-order, phobias restricting normal daily function, social anxiety, and/or paranoia. 2.Current diagnosis of psychiatric disease requiring daily medication, including con-trolled or uncontrolled schizophrenia, history of or treatment of panic disorder, or any other uncontrolled psychiatric condition. 3.History of alcohol abuse (more than an average of 2-drinks per day) within the past 2 years. 4.History of drug abuse. Drug abuse defined as the use of a drug for a non-therapeutic effect. 5.History of smoking within the past year or a history of more than 5 years of consistent daily smoking. 6.Failure of the drug of abuse or ethanol breath tests at screening or check-in. 7.Positive for HIV, or Hepatitis B or C at screening. 8.Blood donation within 30 days of screening or plasma donation within 7 days of screening. 9.Subjects with a history of bleeding disorders or coagulopathies. 10.History of dyspnea, asthma, tuberculosis, chronic obstructive pulmonary disease, sleep apnea or any other ventilatory / lung disease. 11.Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days of screening. 12.Inability to perform acceptable, quality spirometry, and FEV1 <80% of predicted for age, sex and height. 13.Subjects who, in the opinion of the investigator, will not be able to participate optimally in the study. 14.Any surgical or medical condition which might significantly alter the distribution, me-tabolism or excretion of any drug. The investigator should be guided by evidence of any of the following, and be discussed with the sponsor prior to enrollment into the trial: a.history of pancreatic injury or pancreatitis; b.history or presence of liver disease or liver injury; c.history or presence of impaired renal function as indicated by clinically significant elevation in creatinine, BUN/urea, urinary albumin, or clinically significant urinary cellular constituents ; or d.history of urinary obstruction or difficulty in voiding. 15.Subject who has a history of any infectious disease within 4 weeks prior to drug ad-ministration that in the opinion of the investigator, affects the subject’s ability to par-ticipate in the trial. 16.Subjects who are part of the study staff personnel or family members of the study staff personnel. 17.Subjects who have demonstrated allergic reactions (e.g., food, drug, atopic reactions or asthmatic episodes) which, in the opinion of the investigator and sponsor, interfere with their ability to participate in the trial. 18.Subjects who have a history of malignancy. 19.Personal or family history of malignant hyperthermia. 20.Daily consumption of caffeine greater than 5 caffeinated beverages (e.g., coffee, tea, soft drinks).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To determine the respiratory response of low and high doses of doxapram in conjunction with a low dose of opioids in healthy volunteers. To determine the respiratory response of low and high doses of doxapram in conjunction with a low dose of opioids and hypercapnia in healthy volunteers. Part 2: To determine the respiratory response of low and high doses of doxapram in conjunction with hypercapnia in healthy volunteers. Parts 1 and 2: Estimate the reproducibility of sequential treatments under hypercapnic and ambient air conditions;Primary end point(s): Determining the clinical utility of respiratory stimulants over the potential therapeutic dose range in the face of opioid respiratory depression and presences of hypercapnia. ;Timepoint(s) of evaluation of this end point: End points will be evaluated the completion of Part 1 and Part 2;Secondary Objective: Part 1: To determine the respiratory response of a high dose of doxapram in conjunction with a high dose of opioids in healthy volunteers. To evaluate the tolerability of doxapram in conjunction with a low and high dose of opioids in healthy volunteers. Parts 1 and 2: To determine the PK parameters of doxapram in HV with and without administration of opioids. Exploratory Objective(s) Part 1: To evaluate PK-PD relationship of the respiratory responses of doxapram in conjunction with a low and high dose of opioids in healthy volunteers. To evaluate the effect of respiratory stimulants on pain intensity and threshold during a transient ex-perimental pain model in healthy volunteers. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To determine the dose response of doxapram with and without opiates and hypercapnia;Timepoint(s) of evaluation of this end point: End points will be evaluated at the completion of Part 1 and Part 2 | — |
Countries
Netherlands
Contacts
Public ContactClinical Trial Information
Leids Universitair Medisch Centrum (LUMC)
Outcome results
None listed