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Safety, Tolerability, and Effect of TMC207 and Efavirenz in Healthy Volunteers

2021년 10월 28일 업데이트: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase I, Safety, Tolerability, and Pharmacokinetic Interaction Study of Single-Dose TMC207 and Efavirenz in Healthy Volunteers

Common treatments for tuberculosis (TB) can interfere with certain antiretroviral (ARV) medications used to treat HIV. People whose immune systems are weakened by HIV infection are susceptible to TB, so it is important to find treatments for both that can be given in combination. This study will test the safety of combining a new medication for TB with an already approved HIV medication in healthy adults.

연구 개요

상태

완전한

정황

개입 / 치료

상세 설명

Tuberculosis (TB) is the second most deadly infectious disease after HIV. Multidrug-resistant TB (MDR-TB) has emerged as a worldwide epidemic, limiting treatment options. HIV infected people with suppressed immune systems are particularly susceptible to TB, and TB is the leading cause of death among people with HIV. Treating people infected with both HIV and TB is particularly problematic because rifamycins, the drug class usually used to treat TB, lower the effectiveness of certain anti-HIV medications. Studies of pharmacokinetics (PK), the interactions between drugs and body, are needed to determine which anti-TB and anti-HIV medications can be safely and effectively combined. This study will examine TMC207, a new anti-TB medication with the potential to shorten TB treatment time, combined with efavirenz (EFV), an antiretroviral (ARV) medication used in many first-line treatment regimens for HIV. The study will test PK and safety of this combination in healthy volunteers.

Participation in this study will last 49 days. At entry, participants will complete basic assessments, including taking a medical history and completing a physical exam, an eye exam, an electrocardiogram (ECG) to measure heartbeat, a pregnancy test, and a blood test. Certain behaviors and substances will be prohibited during the study, including consuming grapefruit, alcohol, or caffeine (on PK visit days); taking nutritional supplements, over-the-counter herbal medicines, and certain medicines and drugs from other studies; and excessive smoking. Participants will also be asked to keep a medication diary to record all medications they take during the study.

All participants will receive study medications on the same schedule: a single dose of TMC207 on Days 1 and 29, and daily dosing of EFV on Days 15 to 43.

Participants will complete two PK visits, one from Days 1 to 3, and one from Days 28 to 31. During PK visits, participants will have their vital signs checked and undergo an ECG, and they may also complete a limited physical exam, give a medication history, and report on symptoms. They will have multiple blood samples taken via a catheter left in place for the 3-day visit. Blood samples will be taken before receiving TMC207; 1, 2, 3, 4, 5, 6, 8, and 12 hours after receiving TMC207; and again on the mornings of Days 2 and 3.

Participants will complete six outpatient visits over the 11 days following each PK visit and one outpatient visit on Day 21, between PK visits. At outpatient visits participants will complete a blood draw and may complete a limited physical exam and medical history, record symptoms, and review their medication diaries.

On Day 49 participants will complete their last study visit, repeating many of the assessments from baseline testing. In the case of side effects or abnormal blood tests, participants may be monitored longer for safety reasons.

연구 유형

중재적

등록 (실제)

37

단계

  • 1단계

연락처 및 위치

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

연구 장소

  • 미국
    • California
      • San Francisco, California, 미국, 94110
        • Ucsf Aids Crs
    • Maryland
      • Baltimore, Maryland, 미국, 21287
        • Johns Hopkins Adult AIDS CRS
    • North Carolina
      • Chapel Hill, North Carolina, 미국, 27514
        • Unc Aids Crs
    • Ohio
      • Columbus, Ohio, 미국, 43210
        • The Ohio State Univ. AIDS CRS
    • Tennessee
      • Nashville, Tennessee, 미국, 37232-2582
        • Vanderbilt Therapeutics CRS

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, 고령자)

건강한 자원 봉사자를 받아들입니다

예

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Females not of reproductive potential, defined as women who have been postmenopausal for at least 24 consecutive months or women who have undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation
  • Females who have been surgically sterilized and all males must agree to use contraceptives if participating in sexual activity that could lead to pregnancy while receiving the protocol-specified medications and for 4 weeks after stopping the medication
  • Absence of HIV-1 infection, as documented by any licensed enzyme-linked immunosorbent assay (ELISA) test kit, within 21 days prior to study entry
  • Estimated creatinine clearance of more than 50 ml/min, within 21 days prior to study entry, calculated by the Cockcroft-Gault method
  • Laboratory test results obtained within 21 days prior to entry, including negative pregnancy test, negative hepatitis B and C tests, and certain blood values

Exclusion Criteria:

  • Use of any prescription medication known to inhibit or induce CYP3A metabolizing enzymes within 30 days prior to entry
  • Planned use during the study, from day 0 through the last PK blood draw, of any of the following: prescription medication(s), herbal supplement(s), nutritional supplement(s), or over-the-counter medication(s). Multivitamins and acetaminophen, up to 650 mg every 6 hours as an analgesic, are permitted.
  • Hospitalization for any reason, pharmacotherapy for serious illness, or use of any prescription medication(s) within 14 days prior to study entry
  • Receipt of any investigational study drug within 21 days prior to study entry
  • Known allergy, sensitivity, or hypersensitivity to EFV or TMC207 or components of their formulations, including cyclodextrin allergy
  • Significant previous or active history of cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s), as determined by the site investigator. This is inclusive of chronic illnesses or gastrointestinal conditions that may affect drug absorption, etc. Additionally, any medical condition that, in the opinion of the site investigator, would interfere with the volunteer's ability to participate in the protocol will exclude participation.
  • Active illicit drug use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Suspicion of active tuberculosis (TB) by the site investigator
  • Inability to abstain from alcoholic beverages, grapefruit, and grapefruit juice for the duration of the study
  • For smokers, inability to smoke 5 cigarettes per day or less for the duration of the study
  • Breastfeeding
  • Electrocardiogram (ECG) showing first-degree or greater heart block or QT interval (QTc) greater than 440 ms within 21 days prior to study entry. First-degree heart block is defined as PR interval greater than 200 ms.

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: 크로스오버 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: TMC207 alone and with EFV
Participants will receive single-dose TMC207 alone and then single-dose TMC207 with EFV.
의약품: Efavirenz (EFV)
Oral dose of 600 mg daily, taken in the evening
다른 이름들:
  • 수스티바
의약품: TMC207
Single oral dose of 400 mg in the morning

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
기간
Area under curve (AUC) over 336 hours of TMC207, measured when dosed alone and when dosed together with efavirenz (EFV) 600 mg daily
기간: Measured at baseline and Days 1 to 15, 28, and 29 to 43
Measured at baseline and Days 1 to 15, 28, and 29 to 43
Signs or symptoms of toxicity ranked Grade 2 or higher, according to the DAIDS adverse event (AE) grading table
기간: Throughout study
Throughout study

2차 결과 측정

결과 측정
기간
Maximum observed plasma or serum concentration (Cmax) and oral clearance (CL/F) of TMC207 and AUC, Cmax, and CL/F of the M2 metabolite of TMC207 when dosed alone and when dosed together with EFV 600 mg daily
기간: Measured at baseline and Days 1 to 15, 28, and 29 to 43
Measured at baseline and Days 1 to 15, 28, and 29 to 43
AUC over 24 hours, Cmax, Cmin, CL/F, and elimination half-life (T1/2) of EFV and host EFV metabolism genotype status (CYP2B6) obtained from whole blood samples taken at screening
기간: Measured at baseline and on Day 28
Measured at baseline and on Day 28
Correlation between AUC over 24 hours of EFV and AUC over 336 hours of TMC207
기간: Measured at baseline and Days 1 to 15, 28, and 29 to 43
Measured at baseline and Days 1 to 15, 28, and 29 to 43

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Institute of Allergy and Infectious Diseases (NIAID)

수사관

  • 연구 의자: Kelly Dooley, MD, Johns Hopkins University

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

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

2009년 12월 1일

기본 완료 (실제)

2010년 12월 1일

연구 완료 (실제)

2010년 12월 1일

연구 등록 날짜

최초 제출

2009년 10월 1일

QC 기준을 충족하는 최초 제출

2009년 10월 6일

처음 게시됨 (추정)

2009년 10월 8일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2021년 11월 1일

QC 기준을 충족하는 마지막 업데이트 제출

2021년 10월 28일

마지막으로 확인됨

2021년 10월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • A5267
  • 10749 (레지스트리 식별자: DAIDS ES)
  • ACTG A5267

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. .

구독하다