Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents
2018년 7월 20일 업데이트: Gilead Sciences
A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/ Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents
The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.
A total of 50 adolescent participants (12 to < 18 years of age) will be enrolled to receive EVG/COBI/FTC/TDF as follows:
- Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK, and confirm the dose, with the intent to enroll at least 4 participants 12 to < 15 and at least 4 participants 15 to < 18 years of age.
- Part B: Following confirmation of EVG exposure in at least 12 participants from Part A, 34 to 38 participants in addition to those enrolled in Part A will be enrolled to evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.
연구 개요
연구 유형
중재적
등록 (실제)
50
단계
- 2 단계
- 3단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Cape Town, 남아프리카, 7925
- Desmond Tutu HIV Research Centre
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Dundee, 남아프리카, 3000
- Mpati Medical Center
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Johannesburg, 남아프리카, 2092
- Clinical HIV Research Unit
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Soweto, 남아프리카, 2013
- Perinatal HIV Research Unit
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Stellenbosch, 남아프리카, 7602
- University of Stellenbosch
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Gauteng
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Johannesburg, Gauteng, 남아프리카, 2112
- Rahima Moosa Mother and Child Hospital (Wits)
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Kwazulu-Natal
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Durban, Kwazulu-Natal, 남아프리카, 4001
- Dr Latiff Private Practice
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California
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Oakland, California, 미국, 94609
- East Bay AIDS Center Medical Group
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Florida
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Tampa, Florida, 미국, 33606
- University of South Florida - Department of Pediatrics
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Illinois
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Chicago, Illinois, 미국, 60637
- University of Chicago
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New York
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Bronx, New York, 미국, 10467
- Montefiore Medical Center
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New York, New York, 미국, 10016
- New York University School of Medicine
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19134
- St. Christopher's Hospital for Children
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Tennessee
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Memphis, Tennessee, 미국, 38105
- St. Jude Children's Research Hospital
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Bangkok, 태국, 10330
- The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)
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Bangkok, 태국, 10700
- Siriraj Hospital, Mahidol University
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Chon Buri, 태국, 20110
- Queen Savang Vadhana Memorial Hospital
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Khon Kaen, 태국, 40002
- Srinakarind Hospital
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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
12년 (어린이)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Key Inclusion Criteria:
- 12 years to < 18 years of age at baseline
- Able to give written assent prior to any screening evaluations
- Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
- Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL
- CD4+ cell count > 100 cells/µL
- Weight ≥ 35 kg (77 lbs)
- Screening genotype report must show sensitivity to FTC and TDF
- Able to swallow oral tablets
- Adequate renal function
- Clinically normal ECG
- Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a screening visit
- Hepatic transaminases ≤ 5 x upper limit of normal
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Individuals with a positive Hepatitis B surface antigen screening test can participate in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis B infection is available as a part of local standard of care
- Adequate hematologic function
- Negative serum pregnancy test for all females
- Males and females of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days following the last dose of study drug
- Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product
- Must be willing and able to comply with all study requirements
- Life expectancy ≥ 1 year
Key Exclusion Criteria:
- A new AIDS-defining condition diagnosed within the 30 days prior to screening
- Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)
- Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit
- Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study. Note: prophylactic Isoniazid (INH) therapy for latent tuberculosis (TB) treatment is allowed.
- Individuals experiencing decompensated cirrhosis
- Pregnant or lactating females
- Have any serious or active medical or psychiatric illness which would interfere with treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary, endocrine, central nervous, gastrointestinal, vascular, metabolic, immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.
- Current alcohol or substance abuse that will potentially interfere with compliance
- Have history of significant drug sensitivity or drug allergy
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients
- Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study
- A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
- Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing
- Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial
- Receiving ongoing therapy with any disallowed medications, including drugs not to be used with EVG, COBI, FTC, TDF or individuals with any known allergies to the excipients of EVG/COBI/FTC/TDF STR tablets
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: EVG/COBI/FTC/TDF
Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.
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150/150/200/300 mg STR administered orally once daily with food
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
기간: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
기간: Up to Week 48 plus 30 days
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Up to Week 48 plus 30 days
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
기간: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Ctau is defined as the observed drug concentration at the end of the dosing interval.
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
기간: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Cmax is defined as the maximum concentration of drug.
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
기간: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
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Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
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Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
기간: Weeks 24 and 48
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Weeks 24 and 48
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Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
기간: Weeks 24 and 48
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Weeks 24 and 48
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Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
기간: Baseline; Weeks 24 and 48
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Baseline; Weeks 24 and 48
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24주 및 48주에 CD4+ 세포 수의 기준선에서 변화
기간: 기준선 24주 및 48주차
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기준선 24주 및 48주차
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Change From Baseline in CD4 Percentage at Weeks 24 and 48
기간: Baseline; Weeks 24 and 48
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Baseline; Weeks 24 and 48
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
스폰서
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Gaur A, Fourie J, Chokephaibulkit K, Bekker L-G, Yin X, Custodio J, Bennett S, Cheng A, Quirk E. Pharmacokinetics, Efficacy and Safety of an Integrase Inhibitor-Based Single-Tablet Regimen in HIV-Infected Treatment-Naïve Adolescents. 21st Conference on Retroviruses and Opportunistic Infections (CROI). March 2014. Boston, MA, USA
- Chokephaibulkit K, Gaur A, Fourie J, Bekker L-G, Shao Y, Custodio J, Bennett S, Cheng A, Quirk E. Safety and Efficacy of the Integrase Inhibitor-Based Stribild Single-Tablet Regimen in HIV-Infected Adolescents Through 24 Weeks of Treatment. 20th International AIDS Conference. July 2014. Melbourne, Australia
- Porter DP, Bennett S, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). February 2015. Seattle, WA, USA
- Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, Bekker LG, Shao Y, Bennett S, Quirk E. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention. July 2015. Vancouver, Canada
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)
2012년 12월 6일
기본 완료 (실제)
2015년 10월 22일
연구 완료 (실제)
2018년 1월 29일
연구 등록 날짜
최초 제출
2012년 11월 1일
QC 기준을 충족하는 최초 제출
2012년 11월 1일
처음 게시됨 (추정)
2012년 11월 4일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2018년 8월 17일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 7월 20일
마지막으로 확인됨
2018년 7월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- GS-US-236-0112
- 2015-000313-40 (EudraCT 번호)
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
예
미국 FDA 규제 기기 제품 연구
아니
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. .