Study to Investigate Relative Bioavailability of up to Five Different Formulations of AZD5069

An Open-label, Single Centre Relative Bioavailability Study With an Adaptive Design Comparing up to 5 Solid Oral AZD5069 Formulations After Single Dose Administration to Healthy Volunteers

Study to investigate relative bioavailability of up to five different formulations of AZD5069

Study Overview

• Status: Completed
• Conditions: Uncontrolled and Persistent Asthma
• Intervention / Treatment: Drug: Phase IIb formulation; Drug: Putative phase III formulation; Drug: Slow dissolution variant 1; Drug: Slow dissolution variant 2; Drug: Test treatment E

Detailed Description

An Open-label, Single Centre Relative Bioavailability Study With an Adaptive Design Comparing up to 5 Solid Oral AZD5069 Formulations After Single Dose Administration to Healthy Volunteers

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy male and/or female volunteers aged 18 to 50 years (inclusive).
2. Non-smokers or ex-smokers with no smoking history for the last 3 months prior to screening.
3. Body mass index (BMI) ≥18.0 and ≤30.0 kg/m2 calculated from height and weight at screening; minimum (min) weight 50 kg and maximum (max) weight 100 kg.

4. Healthy volunteers with neutrophil counts within the laboratory range at screening.

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Exclusion Criteria:

1. A definite or suspected personal history of severe allergy, intolerance or hypersensitivity or ongoing allergy to drugs with a similar chemical structure or class to AZD5069 and/or the excipients, as judged to be clinically relevant by the Investigator.
2. Healthy volunteers who have previously received AZD5069.
3. Volunteers with latent tuberculosis as suggested by their history and judged by the Investigator; confirmatory testing with eg, Quantiferon(R) -TB Gold may be done if required.
4. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to the first administration of the IP -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Phase IIb formulation	Drug: Phase IIb formulation; Single oral dose 45mg AZD5069
Experimental: Treatment B; Putative phase III formulation	Drug: Putative phase III formulation; Single oral dose 45mg AZD5069
Experimental: Treatment C; Slow dissolution variant 1	Drug: Slow dissolution variant 1; Single oral dose 45mg AZD5069
Experimental: Treatment D; Slow dissolution variant 2	Drug: Slow dissolution variant 2; Single oral dose 45mg AZD 5069
Experimental: Treatment E; Optional treatment that may use one of 3 45 mg (intermediate dissolution variant) of AZD5069	Drug: Test treatment E; Tablet formulation E, 45 mg (intermediate dissolution variant) of AZD5069

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of pharmacokinetics of AZD5069 and its metabolite in terms of area under plasma concentration-time curve from time zero to the time of last quantifiable analyte concentration and extrapolated to infinity (AUC(0-last) and AUC)	Curve taken during each of the 5 treatments	Samples taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Description of pharmacokinetics of AZD5069 and its metabolite in terms of observed maximum plasma concentration (Cmax), plasma concentration measured at 12 hours (C12h), Cmax/C12h ratio, Cmax/AUC ratio, terminal rate constant (λz)	Curve taken during each of the 5 treatments	Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Description of pharmacokinetics of AZD5069 and its metabolite in terms of terminal half-life (t½λz), time to reach maximum plasma concentration (tmax)	Curve taken during each of the 5 treatments	Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose
Description of pharmacokinetics of AZD5069 and its metabolite in terms of apparent systemic clearance (CL/F) (AZD5069 only), and apparent volume of distribution (Vz/F) (AZD5069 only)	Curve taken during each of the 5 treatments	Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of effect on neutrophils in terms of circulating neutrophil numbers reported as absolute circulating neutrophil counts (ANC). The minimum absolute neutrophil count (ANCmin) and the time to ANCmin (ANCtmin)	Samples taken during each of the 5 treatments	Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose
Description of effect on neutrophils in terms of mean of ANC values from predose to 24 hours postdose (ANCmean), the minimum of the ANC ratio values (ANCmin,ratio)	Samples taken during each of the 5 treatments	Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose
Description of effect on neutrophils in terms of the mean of ANC ratio values calculated baseline to 24 hours post dose (ANCmean,ratio)	Samples taken during each of the 5 treatments	Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Olufeyikemi Oluwayi, MD, Quintiles London UK; Study Director: Bengt Larssons, MD, AstraZeneca Mölndal, Sweden

Publications and helpful links

General Publications

• Cullberg M, Arfvidsson C, Larsson B, Malmgren A, Mitchell P, Wahlby Hamren U, Wray H. Pharmacokinetics of the Oral Selective CXCR2 Antagonist AZD5069: A Summary of Eight Phase I Studies in Healthy Volunteers. Drugs R D. 2018 Jun;18(2):149-159. doi: 10.1007/s40268-018-0236-x.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: November 15, 2013
• First Submitted That Met QC Criteria: November 15, 2013
• First Posted (Estimate): November 21, 2013

Study Record Updates

• Last Update Posted (Estimate): June 25, 2015
• Last Update Submitted That Met QC Criteria: June 24, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Relative bioavailability, Healthy volunteers, Neutrophils
• Other Study ID Numbers: D3551C00002