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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01419600
First received: July 28, 2011
Last updated: July 2, 2012
Last verified: July 2012
History of Changes
  Purpose

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


Condition Intervention Phase
Healthy
 Drug: AZD8683
Drug: Placebo to match
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • The time to Cmax (tmax) will be determined for AZD8683 [ 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. ] [ Designated as safety issue: No ]
  • The Terminal half-life (t1/2z)will be determined for the AZD8683 [ 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from zero to infinity (AUC) [ 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 ] [ Designated as safety issue: No ]
  • Apparent plasma clearance (CL/F) [ 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 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution during terminal phase (Vz/F) [ 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 ] [ Designated as safety issue: No ]
  • Mean residence time (MRT) [ 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 ] [ Designated as safety issue: No ]
  • Amount of drug excreted unchanged into urine in a collection interval (Ae) [ 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 ] [ Designated as safety issue: No ]
  • Fraction of dose excreted unchanged in urine (Ae/Dose) [ 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: October 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Drug: AZD8683
Single Dose Inhaled IMP via Turbuhaler
Placebo Comparator: 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.
 Drug: Placebo to match
Single dose Inhaled Placebo via Turbuhaler

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01419600

Locations
United Kingdom
Research Site
London, UK, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Carin Jorup AstraZeneca
Principal Investigator: Darren Wilbraham Quintiles
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01419600     History of Changes
Other Study ID Numbers: D1883C00006, 2011-002412-87
Study First Received: July 28, 2011
Last Updated: July 2, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Comittee

Keywords provided by AstraZeneca:
Phase 1
healthy volunteers
safety
 tolerability
pharmacokinetics
single ascending dose study

ClinicalTrials.gov processed this record on May 16, 2013