Bioavailability and Food Effect Study of Gelatin Formulation and Immediate Release Tablet Formulation of Afuresertib
A Single Center, Randomized, Open-Label, Sequential, Single Dose, 3-Period Crossover Study to Evaluate the Bioavailability and Food Effect of a Gelatin Formulation and Immediate Release Tablet Formulation of Afuresertib, an AKT Inhibitor, in Normal Healthy Volunteers
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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New South Wales
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Randwick, New South Wales, Austrálie, 2031
- GSK Investigational Site
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Provided signed written informed consent
- Healthy Male or female between 18 and 40 years of age inclusive, at the time the informed consent is obtained.
- Body weight >=50 kilograms (kg) and body mass index (BMI) of >=18 and <= 32 kg/meter square (m^2).
- A female subject is eligible to participate if she is of (A) Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy or postmenopausal defined as 12 months of spontaneous amenorrhea (B) Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotropin (hCG) test at Screening and prior to dosing, AND: agrees to use one of the acceptable contraception methods
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods.
- Alanine aminotransferase, alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Based on single or averaged QT interval corrected (QTc) values of triplicate ECGs obtained over a brief recording period: QTcB <450 millisecond (msec); or QTcB <480 msec in subjects with Bundle Branch Block.
- Able to swallow and retain orally administered study treatment and does not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
Exclusion Criteria:
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of gastroesophageal reflux disease, dyspepsia, peptic ulcer disease, gastrointestinal (GI) bleeding, GI surgery that could affect motility.
- History of atrial arrhythmias
- History of regular alcohol consumption within 6 months of the study defined as:
An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 10 grams (g) of alcohol: 270 mL of full strength beer (4.8%), 375 mL of mid strength beer (3.5%), 470 mL of light beer (2.7%), 250 mL pre-mix full strength spirit (5%), 100mL of wine (13.5%) and 30 mL of spirit (40%).
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of Screening.
- Smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- A positive drug/alcohol screen at Screening or upon check-in to the clinic on Day -1 of each Dosing Period.
- A positive test for human immuno virus (HIV) antibody.
- Pregnant females as determined by positive serum hCG test at Screening or prior to dosing.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Lactating females.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
- Any prohibited medications or recent consumption of citrus products.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Experimentální: Sequence 1
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): ABC
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White opaque hard gelatin capsule with a unit dose strength of 25 milligrams (mg) for oral administration
White round biconvex film coated IR tablet with a unit dose strength of 25 mg for oral administration
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Experimentální: Sequence 2
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): ACB
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White opaque hard gelatin capsule with a unit dose strength of 25 milligrams (mg) for oral administration
White round biconvex film coated IR tablet with a unit dose strength of 25 mg for oral administration
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Experimentální: Sequence 3
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): BAC
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White opaque hard gelatin capsule with a unit dose strength of 25 milligrams (mg) for oral administration
White round biconvex film coated IR tablet with a unit dose strength of 25 mg for oral administration
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Experimentální: Sequence 4
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): BCA
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White opaque hard gelatin capsule with a unit dose strength of 25 milligrams (mg) for oral administration
White round biconvex film coated IR tablet with a unit dose strength of 25 mg for oral administration
|
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Experimentální: Sequence 5
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): CAB
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White opaque hard gelatin capsule with a unit dose strength of 25 milligrams (mg) for oral administration
White round biconvex film coated IR tablet with a unit dose strength of 25 mg for oral administration
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Experimentální: Sequence 6
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): CBA
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White opaque hard gelatin capsule with a unit dose strength of 25 milligrams (mg) for oral administration
White round biconvex film coated IR tablet with a unit dose strength of 25 mg for oral administration
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Composite of pharmacokinetic (PK) parameters to determine relative bioavailability of afuresertib after administering it as a single dose in an original gelatin capsule in the fasted state and in a newly formulated IR tablet in the fed and fasted state.
Časové okno: PK Samples will be collected Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 120, and 168 hours post-dose
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PK parameters include: area under the plasma concentration-time curve from time zero to infinity (AUC [0-infinity]), area under the plasma concentration time curve from time zero to last time of quantifiable concentration (AUC [0-t]), maximum observed plasma concentration (Cmax), and time to Cmax (tmax).
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PK Samples will be collected Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 120, and 168 hours post-dose
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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Number of subjects with adverse events (AEs).
Časové okno: Up to 9 weeks
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AEs will be collected from the start of Study Treatment and until the Follow-up contact.
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Up to 9 weeks
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Clinical laboratory parameter assessment as a measure of safety and tolerability
Časové okno: Up to 9 weeks
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Laboratory parameters include: hematology, clinical chemistry and urinalysis.
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Up to 9 weeks
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Concomitant medications review as a measure of safety and tolerability
Časové okno: Up to 9 weeks
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Up to 9 weeks
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Electrocardiogram (ECGs) measurement as a measure of safety and tolerability
Časové okno: Up to 9 weeks
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Triplicate 12-lead ECGs will be collected at Screening; in each Dosing Period on Day 1 and Day 3 of Dosing Period; and at Follow-up.
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Up to 9 weeks
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Vital sign measurement as a measure of safety and tolerability
Časové okno: Up to 9 weeks
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Vital sign measurements will include systolic and diastolic blood pressure and pulse rate.
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Up to 9 weeks
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Composite of PK parameter following single dose administration of IR tablet in fasted state
Časové okno: PK Samples will be collected Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 120, and 168 hours post-dose
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PK parameters include: AUC (0 - infinity), AUC (0 - t), Cmax, and tmax.
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PK Samples will be collected Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 120, and 168 hours post-dose
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Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Aktuální)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další identifikační čísla studie
Další identifikační čísla studie
- 201039
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