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

Phase 1

Completed

• Conditions: Uncontrolled and Persistent Asthma
• Interventions: Drug: Phase IIb formulation; Drug: Putative phase III formulation; Drug: Slow dissolution variant 1; Drug: Slow dissolution variant 2; Drug: Test treatment E

• Registration Number: NCT01989520
• Lead Sponsor: AstraZeneca

Brief Summary

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

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 Timeline

• Study First Submitted: 2013-11-15
• Study First Submitted QC: 2013-11-15
• Study First Posted: 2013-11-21
• Study Start: 2014-01
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-24
• Last Update Posted: 2015-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment A	Phase IIb formulation	Phase IIb formulation
Treatment B	Putative phase III formulation	Putative phase III formulation
Treatment C	Slow dissolution variant 1	Slow dissolution variant 1
Treatment D	Slow dissolution variant 2	Slow dissolution variant 2
Treatment E	Test treatment E	Optional treatment that may use one of 3 45 mg (intermediate dissolution variant) of AZD5069

Primary Outcome Measures

Name	Time	Method
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)	Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose	Curve taken during each of the 5 treatments
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)	Samples taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose	Curve taken during each of the 5 treatments
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)	Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose	Curve taken during each of the 5 treatments
Description of pharmacokinetics of AZD5069 and its metabolite in terms of terminal half-life (t½λz), time to reach maximum plasma concentration (tmax)	Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose	Curve taken during each of the 5 treatments

Secondary Outcome Measures

Name	Time	Method
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)	Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose	Samples taken during each of the 5 treatments
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)	Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose	Samples taken during each of the 5 treatments
Description of effect on neutrophils in terms of the mean of ANC ratio values calculated baseline to 24 hours post dose (ANCmean,ratio)	Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose	Samples taken during each of the 5 treatments

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom