Clinical trial NCT01283984: AZD2115 Single Ascending Dose Study
Official title: A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled AZD2115 After Single Ascending Doses in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Lung Disease Causing Persistent Narrowing of the Airways
Keywords: Safety
tolerability
healthy
inhaled
respiratory disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-01-26
Enrollment: 96
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: AZD2115 Single Ascending Dose Study


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects aged 18 to 45 years with suitable veins for cannulation or repeated venepuncture
* Male subjects should be willing to use barrier contraception ie, condoms with spermicide, from the day of dosing until 3 months after dosing with the investigational product.
* Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg
* Be able to inhale from a Spira nebuliser according to given instructions

Exclusion Criteria:

* Prolonged QTcF \>450 ms or shortened QTcF \<340 ms or family history of long QT syndrome
* Any clinically important abnormalities in heart rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes subjects with any of the following:

  * PR (PQ) interval prolongation \>200 ms (first degree AV block)
  * Intermittent second or third degree AV block (based on screening or pre-dose ECG)
  * Incomplete, full or intermittent bundle branch block (QRS \<110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
  * Abnormal T wave morphology, particularly in the protocol defined primary lead
  * Dropped beats
* History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD2115 and/or excipients
* History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
* Serum potassium concentration of \<3.80 mmol/L on admission (Day -1)

Primary outcomes:
measure: To evaluate the frequency of adverse events of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at screening
measure: To evaluate the laboratory safety assessments of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at screening
measure: To evaluate the vital signs of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at screening
measure: To evaluate the physical examination of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at screening
measure: To evaluate the ECG of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at screening
measure: To evaluate the frequency of adverse events of inhaled single doses of AZD2115
timeFrame: Measurements will be taken pre-dose
measure: To evaluate the frequency of adverse events of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
measure: To evaluate the frequency of adverse events of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at follow up 7-13 days post dose.
measure: To evaluate the laboratory safety assessments of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at pre-dose
measure: To evaluate the laboratory safety assessments of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
measure: To evaluate the laboratory safety assessments of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at follow up 7-13 days post dose.
measure: To evaluate the vital signs of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at pre-dose
measure: To evaluate the vital signs of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
measure: To evaluate the vital signs of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at follow up 7-13 days post dose.
measure: To evaluate the physical examination of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at pre-dose
measure: To evaluate the physical examination of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
measure: To evaluate the physical examination of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at follow up 7-13 days post dose.
measure: To evaluate the ECG of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at pre-dose
measure: To evaluate the ECG of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
measure: To evaluate the ECG of inhaled single doses of AZD2115
timeFrame: Measurements will be taken at follow up 7-13 days post dose.
Secondary outcomes:
measure: To assess the pharmacokinetics of a single dose of AZD2115 by assessment of area under the curve over the time (AUC) and maximum concentration (Cmax).
timeFrame: Frequent sampling occasions during study days, before and up to 48 h after dosing
measure: To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - FEV1
timeFrame: Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
measure: To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - potassium
timeFrame: Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
measure: To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - glucose
timeFrame: Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
measure: To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - systolic and diastolic blood pressure
timeFrame: Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
measure: To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - pulse, heart rate
timeFrame: Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
measure: To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - QTcF
timeFrame: Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
state: UK
Study officials:
References: