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

NCT01962935 | Completed Phase 1

• 1 other identifier: D5200C00002
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chronic Obstructive Pulmonary Disease (COPD).

Keywords

Healthy volunteer; Multiple ascending dose

Outcome Measures

Primary Outcomes (13)

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

  Same for both part A and B

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

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

  Part A AZD4721

  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).

• 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]

  Part A AZD4721

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

• 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],

  Part A AZD4721

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

• 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]).

  Part A AZD4721

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

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

  Part B AZD5069

  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

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

  Part B AZD5069

  Part B day 1 predose, 12h and 24h postdose

• 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]

  Part B AZD5069

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

• 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]).

  Part B AZD5069

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

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

  Part B AZD4721

  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

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

  Part B AZD4721

  Samples taken for part B predose day 1

• 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]

  Part B AZD4721

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

• 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]).

  Part B AZD4721

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

Secondary Outcomes (18)

• 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)

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

• 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)

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

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

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

• 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)

  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

• 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)

  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

Study Arms (3)

Part A AZD4721

EXPERIMENTAL

Part A of the study, multiple ascending doses of AZD4721 will be administrated once daily for 10 days

Drug: AZD4721

Placebo

PLACEBO COMPARATOR

Part A of the study, multiple ascending doses of matching Placebo will be administrated once a daily for 14 days

Drug: Placebo

AZD5069, then AZD4721

ACTIVE COMPARATOR

Part B of the study, subject will participate in two treatment periods (one with AZD5069 administrated for 3 days and the second period with AZD4721 administrated for 14 days) separated by a wash-out period of 6-10 days between the two periods.

Drug: AZD4721; Drug: AZD5069

Interventions

AZD4721 DRUG

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

AZD5069, then AZD4721; Part A AZD4721

Placebo DRUG

Part A - multiple ascending dose daily

Placebo

AZD5069 DRUG

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

AZD5069, then AZD4721

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• 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.).
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

Related Links

• CSR Synopsis

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Leonard Siew, MD

  Quintiles London, UK

  PRINCIPAL INVESTIGATOR

• Bengt Larsson, MD

  Astrazeneca Mölndal, Sweden

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2013
• First Posted: October 16, 2013
• Study Start: November 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: June 25, 2015

Record last verified: 2015-06

Locations

GB (1)