Healthy
Conditions
Keywords
Phase 1, healthy volunteers, safety, tolerability, pharmacokinetics, single ascending dose study
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
Interventions
DRUGAZD8683
Single Dose Inhaled IMP via Turbuhaler
DRUGPlacebo to match
Single dose Inhaled Placebo via Turbuhaler
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate the safety of AZD8683 by assessing physical examination | A physical examination is conducted at screening, day -1, day 3 and again at follow-up. |
| Evaluate the safety of AZD8683 by assessing the frequency of adverse events | Adverse events are captured from screening and captured on each clinic day and on the follow up day. |
| Evaluate the safety of AZD8683 by assessing a panel of laboratory safety assessments | 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. |
| Evaluate the safety of AZD8683 by assessing dECG. | 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. |
| Evaluate the safety of AZD8683 by assessing vital signs (BP and pulse) | 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 |
| Evaluate the safety of AZD8683 by assessing Spirometry | 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
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve from zero to infinity (AUC) | 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 |
| Apparent plasma clearance (CL/F) | 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 |
| Apparent volume of distribution during terminal phase (Vz/F) | 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 |
| Mean residence time (MRT) | 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 |
| Amount of drug excreted unchanged into urine in a collection interval (Ae) | 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 |
| The maximum plasma concentration (Cmax) will be determined for AZD8683 | 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 |
| Cumulative amount of drug excreted unchanged into urine from zero to time 48 h (Ae(0-48)) | 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 |
| To investigate the pharmacodynamics (PD) of inhaled single ascending doses of AZD8683 in healthy subjects including the Forced Expiratory Volume in 1 second (FEV1) | Spirometry for FEV1 is conducted pre-dose and at 5 minutes, 15 minutes, 1 hour, 2 hours and 4 hourspost dose. |
| To investigate the pharmacodynamics (PD) of inhaled single ascending doses of AZD8683 in healthy subjects the Forced Vital Capacity (FVC) parameter | Spirometry for FVC is conducted pre-dose and at 5 minutes, 15 minutes, 1 hour, 2 hours and 4 hourspost dose. |
| To investigate the pharmacodynamics (PD) of inhaled single ascending doses of AZD8683 in healthy subjects the heart rate will be measured | 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 |
| Fraction of dose excreted unchanged in urine (Ae/Dose) | 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 |
| The time to Cmax (tmax) will be determined for AZD8683 | 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. |
| The Terminal half-life (t1/2z)will be determined for the AZD8683 | 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. |
| Area under the plasma concentration-time curve from zero to 24 h (AUC(0-24)) | 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 |
| Area under the plasma concentration-time curve from zero to 48 h (AUC(0-48) | 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 |
| Area under the plasma concentration-time curve from zero to the time of the last measurable concentration (AUC(0-t)) | 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 |
Countries
United Kingdom
Outcome results
None listed