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
Overview
- Phase
- Phase 1
- Intervention
- AZD8683
- Conditions
- Healthy
- Sponsor
- AstraZeneca
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Evaluate the safety of AZD8683 by assessing the frequency of adverse events
- Status
- Completed
- Last Updated
- 13 years ago
Overview
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
Investigators
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
Arms & Interventions
Group 1 - 4, single ascending dose AZD 8683
Subjects will participate in 1 of 4 groups. In each group, 6 subjects will receive AZD8683 and 2 subjects will receive placebo.
Intervention: AZD8683
Group 1-4 single ascending dose Placebo
Subjects will participate in 1 of 4 groups. In each group, 6 subjects will receive AZD8683 and 2 subjects will receive placebo.
Intervention: Placebo to match
Outcomes
Primary Outcomes
Evaluate the safety of AZD8683 by assessing the frequency of adverse events
Time Frame: 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
Time Frame: 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.
Time Frame: 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 physical examination
Time Frame: A physical examination is conducted at screening, day -1, day 3 and again at follow-up.
Evaluate the safety of AZD8683 by assessing vital signs (BP and pulse)
Time Frame: 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
Time Frame: 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
- 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)
- 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)
- 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)
- 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)
- 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)