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Bioavailability and Food Effect Study of Gelatin Formulation and Immediate Release Tablet Formulation of Afuresertib

2017년 11월 8일 업데이트: 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.

연구 개요

연구 유형

중재적

등록 (실제)

18

단계

  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

    • New South Wales
      • Randwick, New South Wales, 호주, 2031
        • GSK Investigational Site

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 (성인)

건강한 자원 봉사자를 받아들입니다

연구 대상 성별

모두

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 크로스오버 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Sequence 1
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): ABC
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
실험적: Sequence 2
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): ACB
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
실험적: Sequence 3
Participants will receive treatment in following sequence in each of the three study periods (one treatment per period): BAC
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
실험적: 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
실험적: 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
실험적: 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

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
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.
기간: 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: 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).
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

2차 결과 측정

결과 측정
측정값 설명
기간
Number of subjects with adverse events (AEs).
기간: Up to 9 weeks
AEs will be collected from the start of Study Treatment and until the Follow-up contact.
Up to 9 weeks
Clinical laboratory parameter assessment as a measure of safety and tolerability
기간: Up to 9 weeks
Laboratory parameters include: hematology, clinical chemistry and urinalysis.
Up to 9 weeks
Concomitant medications review as a measure of safety and tolerability
기간: Up to 9 weeks
Up to 9 weeks
Electrocardiogram (ECGs) measurement as a measure of safety and tolerability
기간: Up to 9 weeks
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.
Up to 9 weeks
Vital sign measurement as a measure of safety and tolerability
기간: Up to 9 weeks
Vital sign measurements will include systolic and diastolic blood pressure and pulse rate.
Up to 9 weeks
Composite of PK parameter following single dose administration of IR tablet in fasted state
기간: 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.
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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2014년 2월 5일

기본 완료 (실제)

2014년 4월 4일

연구 완료 (실제)

2014년 4월 4일

연구 등록 날짜

최초 제출

2014년 1월 16일

QC 기준을 충족하는 최초 제출

2014년 1월 16일

처음 게시됨 (추정)

2014년 1월 20일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2017년 11월 13일

QC 기준을 충족하는 마지막 업데이트 제출

2017년 11월 8일

마지막으로 확인됨

2017년 11월 1일

추가 정보

이 연구와 관련된 용어

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

암에 대한 임상 시험

GSK2110183 Gelatin Capsule에 대한 임상 시험

구독하다