To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of Inhaled AZD8683

Phase 1CompletedNCT01419600

AstraZeneca38 enrolled

Overview

The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of increasing single doses of AZD8683 administered via inhalation

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

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

AZD8683DRUG

Single Dose Inhaled IMP via Turbuhaler

Placebo to matchDRUG

Single dose Inhaled Placebo via Turbuhaler

Eligibility

Sex: MALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Research Site

London, UK, United Kingdom

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

Time frame: 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

Data from ClinicalTrials.gov

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Time frame: 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

Area under the plasma concentration-time curve from zero to 24 h (AUC(0-24))

Time frame: 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)

Time frame: 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))

Time frame: 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)

Apparent plasma clearance (CL/F)

Apparent volume of distribution during terminal phase (Vz/F)

Mean residence time (MRT)

Amount of drug excreted unchanged into urine in a collection interval (Ae)

Fraction of dose excreted unchanged in urine (Ae/Dose)

Cumulative amount of drug excreted unchanged into urine from zero to time 48 h (Ae(0-48))

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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