A Randomized, Crossover Study Comparing Adherence, Preference + Acceptability of a Dual Prevention Pill (DPP) Capsule Containing PrEP + an Oral Contraceptive Versus Two Separate Pills in Women at Risk of HIV in Johannesburg, South Africa
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- To compare adherence to the DPP capsule (Regimen A) versus 2 separate tablets (Regimen B) among women using each regimen daily for 3 28-day menstrual cycles during the Crossover period.
研究概览
简要总结
A randomized, crossover study to compare adherence, preference and acceptability of an over-encapsulated dual prevention pill (DPP capsule) containing oral pre-exposure prophylaxis (PrEP) and a combined oral contraceptive (COC) versus two separate tablets (PrEP and COC) among women at risk of HIV and unintended pregnancy in Johannesburg, South Africa
详细描述
SOUTH AFRICA We will conduct a randomized, open-label, parallel group, 2-way crossover study among approximately 96 women aged 16-40 years old to compare adherence, preference, acceptability and safety of a single dual prevention pill (DPP) containing Truvada and the generic COC, Zinnia F (Regimen A), versus Truvada and Zinnia F taken separately (Regimen B). All participants must already be using COCs for at least 3 months prior to screening and must plan to continue using them for at least one year. We are enrolling women who are already using COCs because we believe they are most likely to be interested in a daily oral MPT. Furthermore, we would like participants who are already accustomed to COCs so that they can have a clearer sense of how PrEP - whether taken separately or in the DPP - makes them feel.
Prior to the commencement of the study, the Population Council procured and qualified all study drugs required for the crossover study, including: bulk pills (Truvada and Zinnia F) for encapsulation, COC pill packs, and bottles of Truvada. Under the guidance of the Council's clinical and regulatory groups, PCI Pharma (Rockford, IL, USA) over-encapsulated Truvada and Zinnia F according to Good Manufacturing Practices. The over-encapsulated pills were then blister packaged, pouched, and kitted for distribution to participants.
The DPP regimen (A) consists of a kit containing 4 pouches with a 28-day supply of over-encapsulated pills; 21 pink and white capsules will contain Truvada over-encapsulated together with a COC; the other 7 capsules, corresponding to the 7 placebo days in a COC pill pack, will be white and will contain Truvada only. The provider counseling manual will emphasize the fact that unlike a COC pill pack where 7 pills are placebo, all of the pills in the regimen contain Truvada, so it will be important to take them for all 28 days. For Regimen B, participants will receive a 28-day blister pack of Zinnia F, as is currently marketed, with 21 active pills and 7 placebo pills. Truvada will be dispensed in bottles of 30 pills, as is currently marketed. Participants will be instructed to take one Truvada tablet and one COC table daily for 28 days.
After providing written informed consent (or assent, with parental consent, for 16-17-year-old girls), women will be screened for eligibility. Participants can be enrolled if they are sexually-active (defined as having had penile-vaginal sex with a male ≤3 months before screening), currently using a COC that was started ≥3 months before screening, HIV-negative (based on HIV rapid test at screening), not-pregnant (based on hCG urine test at screening), have no contraindications for PrEP or COCs, and are in good health based on medical history and vital signs. PrEP screening will follow the standard of care in South Africa, which recommends testing for Hepatitis B, blood creatinine levels, pregnancy, and STIs. Women who test positive for pregnancy or HIV will be referred per the local standard of care. Participants who test positive for a curable STI will be treated and enrolled. Participants who are eligible will be scheduled for an enrollment visit on Day 0 of their menstrual cycle.
At enrollment, women will be randomly assigned to one of two sequences of the two regimens, with all women using both regimens by the end of the crossover study. The Population Council study biostatistician created the randomization scheme using Statistical Analysis Software (SAS/STAT) version 9.4 (SAS Institute Inc., Cary, North Carolina) with a 1:1 allocation using permutated block sizes. Randomization is in blocks of 12, with 6 participants assigned to each sequence in each of 8 blocks. Half of the women will be assigned to Sequence 1, which is Regimen A followed by Regimen B and the other half will be assigned to Sequence 2, which is Regimen B followed by Regimen A. Participants will use each regimen for 3 28-day menstrual cycles and will then switch to the second regimen at their crossover visit. At the end of the crossover period, participants will be offered a choice of Regimen A or Regimen B (or neither) to use for up to an additional 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 40 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age 16 through 40 years old (inclusive) at Screening, verified per site-specific SOPs.
- •Able and willing to provide informed consent per site SOPs. (If under the legal age of consent [18 years old] be able to provide informed assent and obtain parental or guardian consent, to be screened for and to enroll in the study.)
- •Fluent in spoken Zulu and/or English.
- •Able and willing to provide adequate locator information, as defined in site SOPs.
- •Able and willing to comply with all study procedures, including being comfortable taking the study products as evident by nurse/clinician-observed swallowing at Screening of a large Vitamin capsule that is of similar size to the study products.
- •Post-menarche, per participant report at Screening.
- •Sexually active, defined as having had penile-vaginal sex with a male within the 3 months before Screening (per self-report).
- •At moderate to high risk of HIV infection based on clinician assessment.
- •Considers herself to be at moderate to high risk of HIV acquisition based on self-assessment.
- •Has been using COCs for contraception for at least 3 months prior to Screening as confirmed by contraceptive card and intends to continue using COCs for at least 12 months.
- •HIV-negative per rapid test at Screening and Enrolment per site-specific SOP.
- •Negative pregnancy test at Screening and Enrolment.
- •Negative for chlamydia, gonorrhea, trichomoniasis, and syphilis at Screening; women who test positive at Screening may be treated and enrolled.
- •Hepatitis B surface antigen (HBsAG) negative per blood test at Screening.
- •Normal estimated creatinine clearance (eCrCl) ≥ 60 ml/min per blood test at Screening.
排除标准
- •Intends to become pregnant within the next 12 months.
- •Intolerance, adverse reaction, or laboratory abnormality associated with PrEP use in the past.
- •Use of PEP within 3 months of Screening (per self-report).
- •Breastfeeding < 6 months postpartum (per self-report).
- •Less than 6 weeks (≤42 days) postpartum and not breastfeeding (per self-report).
- •For women 35 and older, currently smokes cigarettes (self-report).
- •History of deep vein thrombosis / pulmonary embolism (self-report) or history of thrombophlebitis or thromboembolic disorders at Screening (per self-report or medical records).
- •Prolonged immobilization (self-report).
- •Known thrombogenic mutation/complicated valvular disease (per self-report).
- •Ischemic heart disease (per self-report).
- •Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies (per self-report).
- •Migraines with aura
- •For women over 35 years old, migraines without aura (per self-report).
- •Current breast cancer or within 5 years of past breast cancer (per self-report) or history of carcinoma of the breast or other estrogen-dependent neoplasia reported at Screening.
- •Diabetes with nephropathy, retinopathy, or neuropathy (per self-report).
- •Diabetes for > 20 years (per self-report).
- •Symptomatic gall bladder disease (per self-report).
- •Severe cirrhosis (per self-report).
- •Liver tumor (per self-report).
- •Any other condition the clinician feels would jeopardize the health and wellbeing of the participant.
研究组 & 干预措施
Over-encapsulated DPP
A single, over-encapsulated DPP taken once daily for three 28-day cycles (Regimen A) followed by two separate tablets (oral PrEP and COC) taken once daily for three 28-day cycles (Regimen B)
干预措施: Dual Prevention Pill (Drug)
Two Separate Tablets
Two separate tablets (oral PrEP and COC) taken once daily for three 28-day cycles followed by a single, over-encapsulated DPP taken once daily for three 28-day cycles
干预措施: PrEP tablet and a COC as two separate tablets (Drug)
结局指标
主要结局
To compare adherence to the DPP capsule (Regimen A) versus 2 separate tablets (Regimen B) among women using each regimen daily for 3 28-day menstrual cycles during the Crossover period.
时间窗: At the end of Cycle 3 (each cycle is 28 days)
TFV-DP levels in dried blood spots (DBS) by regimen, and overall, at follow up visits every 4 weeks during Crossover period.
To compare adherence among women who choose the DPP capsule (Regimen A) versus adherence among women who choose 2 separate tablets (Regimen B), each taken daily during the Choice period.
时间窗: At the end of Cycle 3 (each cycle is 28 days)
TFV-DP levels in DBS by regimen, and overall, at follow up visits every 4 weeks during Choice period.
To assess and compare self-reported adherence to Regimen A vs Regimen B during the Crossover period, and to the chosen method during the Choice period.
时间窗: Monthly for up to 48 weeks
Self-assessment of ability to adhere to instructions for product use (DPP capsule, FTC/TDF and COCs as applicable) in CASI interviews at follow up visits every 4 weeks during the Crossover and Choice periods.
To assess and compare adherence to Regimen A vs Regimen B during the Crossover period, and to the chosen method during the Choice period based on pill count.
时间窗: Monthly for up to 48 weeks
Proportion of doses taken vs expected by pill count (DPP capsule, FTC/TDF and COCs as applicable) at follow up visits every 4 weeks during the Crossover and Choice periods.
To determine preference for taking a single DPP capsule versus 2 separate tablets (PrEP and COC) once daily among women after using each regimen for three 28-day cycles.
时间窗: At the end of Cycle 3 (each cycle is 28 days)
Proportion of women who prefer the DPP (Regimen A) vs 2 separate tablets (Regimen B) after using each regimen for 3 28-day cycles, per self-report on computer-assisted self-interviewing (CASI).
To determine if more women choose Regimen A versus Regimen B for the Choice period.
时间窗: At the end of the Crossover period (6 months)
Proportion of women who choose Regimen A vs B for the Choice period.
次要结局
- To compare the safety of Regimen A versus Regimen B among women using each regimen for 3 28-day cycles during the Crossover period, and the safety of Regimen A versus Regimen B among women choosing each regimen during the Choice period.(Monthly for up to 48 weeks)
- To explore facilitators and barriers to use, as well as socio-ecological factors that may be associated with adherence.(Monthly for up to 48 weeks)
- To assess the acceptability of the DPP vs 2 separate tablets taken daily to prevent HIV and unintended pregnancy among women using each regimen for 3 28-day cycles during the Crossover period, and for up to 6 28-day cycles during the Choice period.(3 months, 6 months, 12 months)
- To assess if pre-use opinions are associated with actual experiences and preferences after using each regimen.(Baseline and end of Crossover (6 months))
- To qualitatively understand barriers and facilitators to product use and adherence.(through study completion, an average of 48 weeks)
- To explore if socio-ecological factors, product characteristics and product use experiences are associated with acceptability of the DPP and of 2 separate tablets.(3 months, 6 months, 12 months)