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Completed

NCT Number: NCT01962935

Study to Investigate Safety, Tolerability and Effect of Multiple Dosing With AZD 4721 and/or With AZD 5069

Study to investigate safety, tolerability and effect of multiple dosing with AZD 4721 and/or with AZD 5069

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Key information

Conditions

Chronic Obstructive Pulmonary Disease (COPD). Chronic Disease Disease Attributes Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site

London, United Kingdom

About this study

The purpose of the study is to investigate the safety and tolerability, pharmacokinetics and pharmacodynamics of AZD 4721 in healthy volunteers after once daily administration of multiple ascending doses for 10 days, and an open-label comparison with the pharmacodynamics of AZD5069 given twice daily for 3 days

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 1.Provision of signed and dated, written informed consent prior to any study specific procedures.
  • 2.Healthy male and/or female Caucasian (neither Black/African American nor Japanese) volunteers aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture. ("Healthy" is as determined by medical history and physical examination, clinical laboratory parameters, and ECG and performed before first dose administration.).
  • 3.Healthy volunteers should have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).

Exclusion criteria

  • Pyrexial with a body temperature higher than 37.7°C at Day -1 (Visit 2), or as judged by the investigator.
  • Screening blood neutrophil counts (taken in the morning) not within the laboratory reference range (Visit 1).
  • Other latent or chronic infections (eg, recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection) in the previous 90 days, or history of skin abscesses within the previous 90 days.
  • Clinically significant lower respiratory tract infection not resolved within 4 weeks prior to screening (Visit 1), as determined by the investigator.

Treatment and study plan

AZD4721

Drug

Part A - multiple ascending dose, daily; Part B - one dose decided after part A, daily

Placebo

Drug

Part A - multiple ascending dose daily

AZD5069

Drug

Part B - one dose decided after part A, twice a day

Primary outcomes

  1. Description of the safety profile in terms of Adverse events; blood pressure, heart rate and body temperature; electrocardiograms; clinical chemistry; haematology assessments

    Time frame: From Admission day -1 up to Follow up ( Max 12 weeks)

    Same for both part A and B

  2. Description of neutrophils in terms of absolute blood neutrophil count ratio [ANC ratio], time of ANCmin,ss [ANCtmin,ss],

    Time frame: Samples taken for part A day -1, Day 1 at predose,1h,2h,6h and 12h postdose, predose day 2,3,4,5,6,7,8,9,10 predose and at 1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,36h,48h post last dose ( given day 10).

    Part A AZD4721

  3. Description of neutrophils in terms of minimum ANC during first 24 hours on Day 1 [Part A only, ANCmin,Day 1], time of ANCmin,Day 1 [ANCtmin,Day 1], minimum ANC ratio during first 24 hours on Day 1 [Part A only, ANCmin ratio,Day 1]

    Time frame: Samples taken for Part A Day 1 at predose, 1h,2h,6h12h and 24h postdose.

    Part A AZD4721

  4. Descriptions of neutrophils in terms of minimum ANC during the 24 hours following the last morning dose [ANCmin,ss], mean of ANC values during the 24 hours following the last morning dose [ANCmean,ss],

    Time frame: Samples taken for Part A day10 predose and at 1h,2h,3h,6h,9h,12h,15h,18h,21h,24h post dose

    Part A AZD4721

  5. Description of neutrophils in terms of minimum ANC ratio during the 24 hours following the last morning dose [ANCmin ratio,ss], and mean of ANC ratio values during the 24 hours following the last morning dose [ANCmean ratio,ss]).

    Time frame: Samples taken for Part A day 10 predose and at 1h,2h,3h,6h,9h,12h,15h,18h,21h,24h post dose

    Part A AZD4721

  6. Description of neutrophils in terms of • absolute blood neutrophil count ratio [ANC ratio], time of ANCmin,ss [ANCtmin,ss],

    Time frame: Part B visit 1 day -1, day 1 predose, 12h, day 2 predose, day 3 predose,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Part B AZD5069

  7. Description of neutrophils in terms of • time of ANCmin,Day 1 [ANCtmin,Day 1],

    Time frame: Part B day 1 predose, 12h and 24h postdose

    Part B AZD5069

  8. Description of neutrophile in terms of minimum ANC during the 24 hours following the last morning dose [ANCmin,ss], mean of ANC values during the 24 hours following the last morning dose [ANCmean,ss]

    Time frame: Samples taken Part B day 3 predose,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Part B AZD5069

  9. Description of neutrophils in terms of minimum ANC ratio during the 24 hours following the last morning dose [ANCmin ratio,ss], and mean of ANC ratio values during the 24 hours following the last morning dose [ANCmean ratio,ss]).

    Time frame: Samples taken Part B day 3 predose,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Part B AZD5069

  10. Description of neutrophils in terms of • absolute blood neutrophil count ratio [ANC ratio], time of ANCmin,ss [ANCtmin,ss]

    Time frame: Samples taken for part B day -1, predose day 1,2,4,6,8,10 and at 1h,2h,3h,6h,9h,12h,15h,18h,21h,24h post dose

    Part B AZD4721

  11. Description of neutrophils in terms of time of ANCmin,Day 1 [ANCtmin,Day 1],

    Time frame: Samples taken for part B predose day 1

    Part B AZD4721

  12. Description of neutrophils in terms of minimum ANC during the 24 hours following the last morning dose [ANCmin,ss], mean of ANC values during the 24 hours following the last morning dose [ANCmean,ss]

    Time frame: Samples taken part B pre dose day 10 and at 1h,2h,3h,6h,9h,12h,15h,18h,21h,24h post dose

    Part B AZD4721

  13. Description of neutrophils in terms of minimum ANC ratio during the 24 hours following the last morning dose [ANCmin ratio,ss], and mean of ANC ratio values during the 24 hours following the last morning dose [ANCmean ratio,ss]).

    Time frame: Samples taken part B pre dose day 10 and at 1h,2h,3h,6h,9h,12h,15h,18h,21h,24h post dose

    Part B AZD4721

Secondary outcomes

  1. Description of the pharmacokinetic(PK) profile of AZD 4721 in terms of Maximum plasma concentration (Cmax), maximum plasma concentration divided by dose (Cmax/D), time to Cmax (tmax)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h.

    Following single dose administration of AZD4721 Part A

  2. Description of the PK profile of AZD 4721 in terms of area under the plasma concentration-time curve during the dosing interval (AUCtau),), lag-time (tlag), ratio of metabolite AUCtau to parent AUCtau (MRAUC)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h.

    Following single dose administration of AZD4721 Part A

  3. Description of the PK profile of AZD 4721 in terms of ratio of metabolite Cmax to parent Cmax (MRCmax)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h.

    Following single dose administration of AZD4721 Part A

  4. Description of the PK profile of AZD 4721 in terms of Maximum plasma concentration (Css,max), maximum plasma concentration divided by dose (Css,max/D) time to Css,max (tss,max)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h. Predose day 3,4,5,6,7,8,9,10 and at 0:20,0:40,1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,48h,72h and 96h post last dose

    Following multiple dose administration of AZD4721Part A

  5. Description of the PK profile of AZD 4721 in terms of minimum plasma concentration (Css,min)), time to Css,min (tss,min) average concentration over the investigational product interval (Css,av)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h. Predose day 3,4,5,6,7,8,9,10 and at 0:20,0:40,1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,48h,72h and 96h post last dose

    Following multiple dose administration of AZD4721 Part A

  6. Description of the PK profile of AZD 4721 in terms of peak to trough concentration ratio (Css,max/Css,min)), terminal rate constant (z), terminal half-life (t1/2λz)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h. Predose day 3,4,5,6,7,8,9,10 and at 0:20,0:40,1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,48h,72h and 96h post last dose

    Following multiple dose administration of AZD4721 Part A

  7. Description of the PK profile of AZD 4721 in terms of area under the plasma concentration-time curve during the dosing interval at steady state (AUCss,tau), AUCss,tau divided by dose (AUCss,tau/D)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h. Predose day 3,4,5,6,7,8,9,10 and at 0:20,0:40,1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,48h,72h and 96h post last dose

    Following multiple dose administration of AZD4721Part A

  8. Description of the PK profile of AZD 4721 in terms of apparent clearance (CL/F), ), volume of distribution (Vz/F)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h. Predose day 3,4,5,6,7,8,9,10 and at 0:20,0:40,1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,48h,72h and 96h post last dose

    Following multiple dose administration of AZD4721 Part A

  9. Description of the PK profile of AZD 4721 and metabolite in terms of ratio of metabolite AUCss,tau to parent AUCss,tau (MRAUCss,tau), ratio of metabolite Css,max to parent Css,max (MRCss,max)

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h. Predose day 3,4,5,6,7,8,9,10 and at 0:20,0:40,1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,48h,72h and 96h post last dose

    Following multiple dose administration of AZD4721 Part A

  10. Description of the PK profile of AZD 4721 and metabolite in terms of accumulation ratio for AUCtau (RAUCtau), and accumulation ratio for Cmax (RCmax).

    Time frame: Sample taken Day 1 post dose at 0:20, 0:40,1h, 2h,3h,6h,9h,12h,15h,18h,21h and 24h. Predose day 3,4,5,6,7,8,9,10 and at 0:20,0:40,1h,2h,3h,6h,9h,12h,15h,18h,21h,24h,48h,72h and 96h post last dose

    Following multiple dose administration of AZD4721 Part A

  11. Description of the PK profile of AZD 4721 in terms of Cumulative amount of AZD4721 and AZ13622093 excreted over the investigational product administration interval (Ae (0-tau))

    Time frame: Urine collection 24h from 0h-24 day 10

    Following multiple dose administration of AZD4721 Part A

  12. Description of the PK profile of AZD 4721 in terms of fraction of dose excreted into the urine over the dosing interval for AZD4721 (fe (0 tau)), and renal clearance (CLR).

    Time frame: Urine collection 24h from 0h-24 day 10

    Following multiple dose administration of AZD4721 Part A

  13. Description of PK Profile of AZD5069 in terms of observed global maximum concentration (Css,max), time to global Css,max (tss,max), observed global minimum concentration (Css,min)

    Time frame: Sample taken day 1 12h, day 2 0h and 12h, day 3 0h,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Following multiple dosing of AZD5069 Part B

  14. Description of PK Profile of AZD5069 in terms of time to global Css,min (tss,min), average concentration over 24 hours (Css,av), peak to trough concentration ratio (Css,max/Css,min)

    Time frame: Sample taken day 1 12h, day 2 0h and 12h, day 3 0h,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Following multiple dosing of AZD5069 Part B

  15. Description of PK Profile of AZD5069 in terms of AUC during the 12 hour interval after the morning dose(AUCtau,morning), AUC during the 12 hour dosing interval after the evening dose (AUCtau,evening)

    Time frame: Sample taken day 1 12h, day 2 0h and 12h, day 3 0h,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Following multiple dosing of AZD5069 Part B

  16. Description of PK Profile of AZD5069 in terms of and area under the plasma concentration time curve 0 to 24 hours post morning dose (AUC(0 24h)).

    Time frame: Sample taken day 1 12h, day 2 0h and 12h, day 3 0h,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Following multiple dosing of AZD5069 Part B

  17. Description of PK Profile of AZD4721 in terms of maximum plasma concentration (Css,max), time to Css,max (tss,max), minimum plasma concentration (Css,min), time to Css,min (tss,min), average concentration over the dosing interval (Css,av)

    Time frame: Sample taken predose Day 2,4,6,8,10 and at 0:20h,0:40h,1h,2h,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Following multiple dosing of AZD4721 Part B

  18. Description of PK Profile of AZD4721 in terms of peak to trough concentration ratio (Css,max/Css,min), area under the plasma concentration time curve during the dosing interval (AUCss,tau), and apparent clearance (CL/F).

    Time frame: Sample taken predose Day 2,4,6,8,10 and at 0:20h,0:40h,1h,2h,3h,6h,9h,12h,15h,18h,21h and 24h post dose

    Following multiple dosing of AZD4721 Part B

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Phase I Study in Healthy Volunteers to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD4721 After Once Daily Administration of Multiple Ascending Doses for 10 Days, and an Open-label Comparison With the Pharmacodynamics of AZD5069 Given Twice Daily for 3 Days

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Oct 16, 2013
Registry last updated
Jun 25, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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