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This will be a randomized, open-label, sequential, single dose, 4-period crossover study. This study is being conducted to measure the relative bioavailability of the original gelatin capsule (GC) formulation and two new formulations (hydroxypropyl-methylcellulose [HPMC] capsule and enteric coated tablet [ECT]) of afuresertib (AFU), in the fed and fasted state. The study will be composed of Screening, Treatment, and Follow-up Periods. Screening assessments to determine subject eligibility will be performed within 3 weeks prior to the first dose of study drug in the Treatment Period. Eligible subjects will be randomized to receive 4 of the 6 possible study treatments (A: AFU GC administered in a fasted state, B: AFU GC administered in a fed state, C: AFU HPMC capsule administered in a fasted state, D: AFU HPMC capsule administered in a fed state, E: AFU ECT administered in a fasted state, F: AFU ECT administered in a fed state) in 4 treatment periods (one per treatment period). Subjects will receive a single dose of one of the six study treatments (A, B, C, D, E, F) on Day 1 of each Dosing Period, according to one of the 6 treatment sequences (CEDA, EFAB, ABFC, BDCE, FCBD, DAEF). There will be a minimum of 10 Day washout period between the doses administered in each Treatment Period. A Follow-up visit will be conducted within 10-14 days after the last dose. A subject's total time involved in the study will be approximately 9 weeks. At least 36 subjects will be enrolled in the study, to ensure that at least 6 subjects will be randomized to receive each treatment sequence.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | Subjects will receive single doses of AFU HPMC capsule administered in a fasted state, AFU ECT administered in a fasted state, AFU HPMC capsule administered in a fed state and AFU GC administered in a fasted state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period |
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| Sequence 2 | Experimental | Subjects will receive single doses of AFU ECT administered in a fasted state, AFU ECT administered in a fed state, AFU GC administered in a fasted state and AFU GC administered in a fed state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period. |
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| Sequence 3 | Experimental | Subjects will receive single doses of AFU GC administered in a fasted state, AFU GC administered in a fed state, AFU ECT administered in a fed state and AFU HPMC capsule administered in a fasted state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Afuresertib GC - Fasted State | Drug | White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fasted state |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of plasma pharmacokinetics (PK) parameters of afuresertib, following administration with and without food | Relative bioavailability of afuresertib after single dose of a GC, HPMC capsule and ECT, with and without high fat/calorie meal, will be determined by the following PK parameters: Area under the plasma concentration time curve- from time zero (pre-dose) to infinite time [AUC(0-inf)] and from time zero (pre-dose) to last time of quantifiable concentration [AUC(0-t)], maximum observed plasma concentration (Cmax), time to Cmax (tmax), observed plasma concentration at 24 hours (C24), and minimal observed plasma concentration (Ct) | PK samples will be collected at Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours post-dose in each dosing period |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of afuresertib as assessed by number of subjects with adverse events (AEs) | AEs will be collected from the start of Study Treatment and until the Follow-up contact | Up to 9 weeks |
| Safety and tolerability of afuresertib as assessed by clinical laboratory tests |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Melbourne | Victoria | 3004 | Australia |
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| Label | URL |
|---|---|
| Results for study 117313 can be found on the GSK Clinical Study Register. | View source |
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| Sequence 4 | Experimental | Subjects will receive single doses of AFU GC administered in a fed state, AFU HPMC capsule administered in a fed state, AFU HPMC capsule administered in a fasted state and AFU ECT administered in a fasted state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period |
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| Sequence 5 | Experimental | Subjects will receive single doses of AFU ECT administered in a fed state, AFU HPMC capsule administered in a fasted state, AFU GC administered in a fed state and AFU HPMC capsule administered in a fed state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period |
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| Sequence 6 | Experimental | Subjects will receive single doses of AFU HPMC capsule administered in a fed state, AFU GC administered in a fasted state, AFU ECT administered in a fasted state and AFU ECT administered in a fed state (sequentially), on Day 1 of Dosing Period 1, 2, 3 and 4 (one treatment per period) respectively, with a minimum 10 Day washout between the doses in each Dosing Period |
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| Afuresertib HPMC capsule - Fasted State | Drug | White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fasted state |
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| Afuresertib ECT - Fasted State | Drug | White to off white, round, biconvex coated tablet containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib ECT administered in fasted state |
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| Afuresertib GC - Fed State | Drug | White opaque hard gelatin capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib GC administered in fed state |
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| Afuresertib HPMC capsule - Fed State | Drug | White opaque HPMC capsule containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib HPMC capsule administered in fed state |
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| Afuresertib ECT - Fed State | Drug | White to off white, round, biconvex coated tablet containing afuresertib 25 mg. Subjects will receive single oral dose of afuresertib ECT administered in fed state |
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Hematology, clinical chemistry and urinalysis parameters will be measured |
| Up to 9 weeks |
| Safety and tolerability of afuresertib as assessed by concomitant medications review | Up to 9 weeks |
| Safety and tolerability of afuresertib as assessed by electrocardiograms (ECG) measurements | Triplicate 12-lead ECGs will be collected at Screening; on Day 1 and Day 3 of each Dosing Period; and at Follow-up | Up to 9 weeks |
| Safety and tolerability of afuresertib as assessed by vital signs measurement | Vital sign measurements will include systolic and diastolic blood pressure and pulse rate | Up to 9 weeks |
| Change in phosphoAKT (pAKT) levels in peripheral blood samples following administration of a gelatin capsule, HPMC capsule and ECT | The potential relationship between plasma PK and pharmacodynamic biomarker changes (pAKT) of each formulation will be evaluated | Pre-dose and 2, 12, and 24 hours post-dose in each dosing period. |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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