- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT02040480
Bioavailability and Food Effect Study of Gelatin Formulation and Immediate Release Tablet Formulation of Afuresertib
8. november 2017 oppdatert av: GlaxoSmithKline
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
This study is being conducted to measure the relative bioavailability of the original gelatin capsule formulation and a new formulation, immediate release (IR) tablet of Afuresertib (GSK2110183).
The study will be composed of Screening, Treatment, and Follow-up Periods.
A subject's total time involved in the study will be approximately 9 weeks.
The study will enroll approximately 18 healthy volunteers.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
18
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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New South Wales
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Randwick, New South Wales, Australia, 2031
- GSK Investigational Site
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 40 år (Voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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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Eksperimentell: 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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Eksperimentell: 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
|
|
Eksperimentell: Sequence 4
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): BCA
|
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
|
|
Eksperimentell: Sequence 5
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): CAB
|
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
|
|
Eksperimentell: Sequence 6
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): CBA
|
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
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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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.
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Number of subjects with adverse events (AEs).
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
5. februar 2014
Primær fullføring (Faktiske)
4. april 2014
Studiet fullført (Faktiske)
4. april 2014
Datoer for studieregistrering
Først innsendt
16. januar 2014
Først innsendt som oppfylte QC-kriteriene
16. januar 2014
Først lagt ut (Anslag)
20. januar 2014
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
13. november 2017
Siste oppdatering sendt inn som oppfylte QC-kriteriene
8. november 2017
Sist bekreftet
1. november 2017
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- 201039
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