Clinical trial NCT01419600: To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of Inhaled AZD8683
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 AZD8683 After Single Ascending Doses Administered Via Turbuhaler in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Phase 1
healthy volunteers
safety
tolerability
pharmacokinetics
single ascending dose study
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-08-18
Enrollment: 38
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: The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of increasing single doses of AZD8683 administered via inhalation

Detailed description: A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of inhaled AZD8683 after Single Ascending Doses administered via Turbuhaler in Healthy Subjects

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated, written informed consent prior to any study specific procedures Healthy male subjects aged 18
* 45 years with suitable veins for cannulation or repeated venepuncture
* Male subjects should be willing to use barrier contraception ie, condoms and spermicide, from the day of dosing until at least 3 months after dosing with the investigational product
* Have a body mass index (BMI) between 19 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive

Exclusion Criteria:

* History or presence of gastrointestinal, pulmonary, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
* Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the investigational product
* Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:

  * Systolic blood pressure \>140 mm Hg
  * Diastolic blood pressure \>90 mm Hg
  * Heart rate \<40 or \>85 beats per minute Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG. This includes subjects with any of the following:
  * PR(PQ) interval prolongation \>200 ms or dropped beats (single non conducted P-waves) based on screening or Prolonged QTcF \>450 ms or shortened QTcF \<340 ms or family history of long QT syndrome

Primary outcomes:
measure: Evaluate the safety of AZD8683 by assessing the frequency of adverse events
timeFrame: Adverse events are captured from screening and captured on each clinic day and on the follow up day.
measure: Evaluate the safety of AZD8683 by assessing a panel of laboratory safety assessments
timeFrame: Lab safety assessments are taken at screening, pre-dose on day 1 and then 24 hours, and 48 hours post-dose and again on follow up.
measure: Evaluate the safety of AZD8683 by assessing dECG.
timeFrame: dECG is conducted pre-dose and then 15 minutes, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 8 hours 12 hours, 24 hours and 48 hours post dose.
measure: Evaluate the safety of AZD8683 by assessing physical examination
timeFrame: A physical examination is conducted at screening, day -1, day 3 and again at follow-up.
measure: Evaluate the safety of AZD8683 by assessing vital signs (BP and pulse)
timeFrame: Vital signs are measured at screening, pre-dose and then 15 minutes, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours and 48 hours post dose
measure: Evaluate the safety of AZD8683 by assessing Spirometry
timeFrame: Spirometry is conducted pre-dose and at 5 minutes, 15 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours
Secondary outcomes:
measure: The maximum plasma concentration (Cmax) will be determined for AZD8683
timeFrame: pre-dose and than 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: The time to Cmax (tmax) will be determined for AZD8683
timeFrame: pre-dose and then 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose.
measure: The Terminal half-life (t1/2z)will be determined for the AZD8683
timeFrame: pre-dose and then 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose.
measure: Area under the plasma concentration-time curve from zero to 24 h (AUC(0-24))
timeFrame: pre-dose and than 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours post dose
measure: Area under the plasma concentration-time curve from zero to 48 h (AUC(0-48)
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours post dose
measure: Area under the plasma concentration-time curve from zero to the time of the last measurable concentration (AUC(0-t))
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: Area under the plasma concentration-time curve from zero to infinity (AUC)
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: Apparent plasma clearance (CL/F)
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: Apparent volume of distribution during terminal phase (Vz/F)
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: Mean residence time (MRT)
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: Amount of drug excreted unchanged into urine in a collection interval (Ae)
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: Fraction of dose excreted unchanged in urine (Ae/Dose)
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours and 120 hours post dose
measure: Cumulative amount of drug excreted unchanged into urine from zero to time 48 h (Ae(0-48))
timeFrame: 0 minutes, 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours post dose
measure: To investigate the pharmacodynamics (PD) of inhaled single ascending doses of AZD8683 in healthy subjects including the Forced Expiratory Volume in 1 second (FEV1)
timeFrame: Spirometry for FEV1 is conducted pre-dose and at 5 minutes, 15 minutes, 1 hour, 2 hours and 4 hourspost dose.
measure: To investigate the pharmacodynamics (PD) of inhaled single ascending doses of AZD8683 in healthy subjects the Forced Vital Capacity (FVC) parameter
timeFrame: Spirometry for FVC is conducted pre-dose and at 5 minutes, 15 minutes, 1 hour, 2 hours and 4 hourspost dose.
measure: To investigate the pharmacodynamics (PD) of inhaled single ascending doses of AZD8683 in healthy subjects the heart rate will be measured
timeFrame: Heart rate is measured pre-dose and then at 15 minutes, 30 minutes, 1 hour, 1 hour 30 minutes, 2 hours and 4 hours post dose
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
state: UK
Study officials:
affiliation: AstraZeneca
name: Carin Jorup
role: STUDY_DIRECTOR
affiliation: Quintiles, Inc.
name: Darren Wilbraham
role: PRINCIPAL_INVESTIGATOR
References: