Phase 1 Open Label Safety, Acceptability, Pharmacokinetic and ex Vivo Pharmacodynamic Study of TMC278 Long Acting (LA) Administered Intramuscularly to HIV-1 Seronegative Individuals
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 主要终点
- Number of participants who would consider using long acting TMC278 for Human immunodeficiency virus (HIV) prevention in the future
研究概览
简要总结
The purpose of this study is to evaluate the safety, acceptability, pharmacokinetics (what the body does to the medication), and ex vivo (tested outside the body) pharmacodynamics (what the medication does to the body) of TMC278 long acting (slowly effective after initial dosage and maintaining its effects over a long period of time) when administered as an intramuscular (ie, in to the muscle) injection in adult participants who are seronegative for human immunodeficiency virus type 1 (HIV-1).
详细描述
This is an open-label (all people know the identity of the intervention), multi-arm (more than one treatment group), dose-ranging study (clinical study where different doses of study medication are tested against each other) to evaluate the safety, acceptability, pharmacokinetics, and ex vivo pharmacodynamics of a single and multiple intramuscular injections of long acting TMC278 to human immunodeficiency virus type 1 (HIV-1) seronegative (having a negative serum reaction) male and female participants. The study consists of 3 phases including screening phase, treatment phase, and the follow up phase (approximately 4 to 6 months after the first dose of study medication). In treatment phase, enrolled participants will be divided in to 2 arms, ie, Arm A (female participants) which will be further divided in to Arm 1A, Arm 2A, Arm 3A, Arm 4A, and Arm 5A with 12 female participants per arm; and Arm B (male participants) which will be further divided in to Arm 1B, Arm 2B, Arm 3B, Arm 4B, and Arm 5B with 6 male participants per arm. Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, physical examination, and vital signs which will be monitored throughout the study. The total duration of study for each participant will be approximately 5 to 7 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Human immunodeficiency virus type 1 (HIV-1) seronegative at screening and enrollment
- •Not pregnant or breastfeeding females
- •Agrees to protocol-defined method of contraception
- •Abstinence from insertion of anything in rectum (eg, medication, enema, penis, or sex toy) for 72 hours before and 72 hours after each rectal biopsy visit
- •Abstinence from insertion of anything in vagina (eg, tampon, medication, douche, penis, or sex toy) for 72 hours before and 72 hours after each cervical and vaginal biopsy visit
排除标准
- •Post-exposure prophylaxis for HIV exposure within 6 months prior to screening and known HIV-infected partners
- •Use of systemic immunomodulatory medications within the 4 weeks prior to the enrollment
- •Use of vaginally or rectally administered medications or products (including condoms) containing Nonoxynol-9 (N-9) within the 4 weeks prior to the enrollment
- •Abnormalities of the cervical, vaginal, or colorectal mucosa, or significant symptom(s), which in the opinion of the clinician represents a contraindication to protocol-required biopsies
- •History of recurrent urticaria
- •History of or electrocardiogram demonstrating prolonged QT interval
- •History of significant gastrointestinal bleeding
研究组 & 干预措施
Arm 1A
Female participants will receive a single dose of long acting TMC278 1200 mg intramuscularly (IM) at baseline (Day 0) in Arm 1A.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 1B
Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline in Arm 1B.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 2A
Female participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2A.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 2B
Male participants will receive a single dose of long acting TMC278 600 mg IM at baseline in Arm 2B.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 3A
Female participants will receive 3 bi-monthly injections of long acting TMC278 1200 mg IM at baseline, Months 2 and 4 in Arm 3A.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 3B
Male participants will receive 3 bi-monthly injections of long acting TMC278 1200 mg IM at baseline, Months 2 and 4 in Arm 3B.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 4A
Female participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 900 mg at Months 2 and 4 in Arm 4A.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 4B
Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 900 mg at Months 2 and 4 in Arm 4B.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 5A
Female participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 600 mg at Months 2 and 4 in Arm 5A.
干预措施: TMC278, Long acting (LA) (Drug)
Arm 5B
Male participants will receive a single dose of long acting TMC278 1200 mg IM at baseline followed by TMC278 600 mg at Months 2 and 4 in Arm 5B.
干预措施: TMC278, Long acting (LA) (Drug)
结局指标
主要结局
Number of participants who would consider using long acting TMC278 for Human immunodeficiency virus (HIV) prevention in the future
时间窗: Up to 280 days
Number of participants with adverse events
时间窗: Up to 280 days
次要结局
- TMC278 concentration in vaginal tissue(Up to 280 days)
- TMC278 concentration in endocervical fluid(Up to 280 days)
- TMC278 concentration in cervical tissue(Up to 280 days)
- TMC278 concentration in vaginal fluid(Up to 280 days)
- TMC278 concentration in rectal tissue(Up to 280 days)
- TMC278 concentration in plasma(Up to 280 days)
- TMC278 concentration in rectal fluid(Up to 280 days)