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The main purpose of the study is to compare the change of the AZD5069 Pharmacokinetic profile when administered with ketoconazole. Subjects will be treated first with AZD5069 only followed by a washout period before starting with the combined treatment (both ketoconazole and AZD5069).
An open-label, fixed-sequence, single-centre phase I study to assess the effect of ketoconazole on the pharmacokinetics of AZD5069 after oral administration of a single dose AZD5069 to healthy male volunteers
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| First AZD5069, then Ketoconazole + AZD5069 | Experimental | AZD5069 in first period (on 1 day) and in second period (after wash out) ketoconazole alone (on 2 days) then ketoconazole + AZD5069 (on 1 day), then again ketoconazole alone (on 2 days) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD5069 | Drug | AZD5069 15 mg (3x5 mg capsules) single administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of AZD5069 (15 mg) and a metabolite (AZ13587715) measured by AUC, AUC(0-t), Cmax, λz, t½λz, tmax, CL/F (AZD5069 only), Vz/F (alone and in combination with Ketoconazole) | (AUC(0-t)) area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, (Cmax) observed maximum plasma concentration, (λz) terminal rate constant, (t½λz) terminal half-life, (tmax) time to reach maximum plasma concentration (tmax), (CL/F) apparent oral clearance (AZD5069 only), (Vz/F) apparent volume of distribution. | Day 1, Day 2 at 24 hours post dose and Day 3 at 48 hours post dose in period 1 and Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2. |
| Pharmacokinetics of Ketoconazole measured by AUC(0-t) and Cmax (in combination with AZD5069) | Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2. |
| Measure | Description | Time Frame |
|---|---|---|
| Numbers of circulating neutrophil in blood measured by AZD5069 administration alone and in combination with Ketoconazole | Day 1, 2, 3 at predose, 4, 8, 12, 24, 48 hours post dose in period 1 and Day 1, 2, 3, 4 at predose, 4, 8, 12, 24, 48 hours post dose | |
| Safety of AZD5069 (15 mg) in combination with Ketoconazole by assessing a panel of adverse events measures: laboratory assessments, vital signs, physical examination and 12-led electrocardiogram. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bengt Larsson, Dr. | AstraZeneca Pharmaceutical | Study Director |
| Gillian Pilbrow | AstraZeneca Pharmaceutical | Study Chair |
| Leonard Siew, DR. | Quintiles Drug Research Unit at Guy's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| London | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29856004 | Derived | 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. |
| Label | URL |
|---|---|
| CSR Synopsis | View source |
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| Ketoconazole | Drug | Ketoconazole 400 mg (2x200 mg tablets) |
|
Measures: laboratory assessments (clinical chemistry, haematology, urinalysis), vital signs (blood pressure, pulse rate, including body temperature), physical examination and 12-led electrocardiogram. |
| Up to 2 months |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000597960 | N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide |
| D007654 | Ketoconazole |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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