A Phase 4 Open Label Study to Assess the Safety and Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in People Living With HIV/AIDS (PLWHA) With Non-Infectious Diarrhea
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 3
- 主要终点
- Changes in gut microbiome
研究概览
简要总结
This study is intended to evaluate:
- Any changes in the gut microbiome from baseline compared to end of study in both healthy (HIV-negative) subjects and HIV+ patients with or without chronic diarrhea, following one month of treatment with crofelemer (Mytesi), delayed release 125 mg tablets twice daily (BID) following one month of treatment.
- The safety and tolerability of crofelemer, (Mytesi) delayed release 125 mg tablets BID in healthy (HIV-negative) volunteers and HIV+ patients following one month of treatment.
详细描述
Mytesi ®(crofelemer) is an FDA-approved anti-diarrheal drug indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on combination anti-retroviral therapy (CART). Crofelemer, a first-in-class intraluminally active, use-dependent chloride (Cl-) ion channel modulator that produces an antidiarrheal effect by reducing Cl- secretion and the accompanying high-volume fluid secretion into the GI lumen.
This Phase 4 trial will explore the induced gut microbiome changes in comparison to a group of normal healthy volunteers also receiving crofelemer delayed release 125 mg tablets twice daily for 30 days.
This is a non-randomized study. The study will enroll approximately 24 male or female subjects aged at least 18 years in three cohorts of approximately 8 subjects each.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Voluntary informed consent from the subject to be obtained in accordance with requirements of the Institutional Review Board (IRB) before any study-related activities are performed.
- •Body Mass Index (BMI) between 18 and 32 kg/m2 (both inclusive).
- •Females of child-bearing potential must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test at Visit
- •Inclusion Criteria for Healthy, HIV-negative Volunteers
- •No history or evidence of clinically relevant medical disorders as determined by the investigator.
- •No history of chronic diarrhea or loose stools and/or non-specific incidence of acute diarrhea or loose stools between the Screening Visit and Baseline Visit 2 (Day 1).
- •Inclusion Criteria applicable to all PLWHA subjects
- •Male and female patients receiving a stable CART for ≥ 4 weeks for HIV treatment.
- •Have a history of diarrhea (persistently loose stools despite periodic or regular use of antimotility medications) or ≥1 watery bowel movement per day (without periodic or regular use of antimotility drugs); i.e. - diarrhea for a continuous period of ≥1 month.
- •Inclusion Criteria for PLWHA males and females receiving CART WITHOUT fully suppressed HIV RNA counts
- •CD4 counts >200/µL at the Screening Visit.
- •Plasma levels of HIV RNA greater than 1,000 copies/mL at the Screening Visit.
- •Inclusion Criteria for PLWHA males and females receiving CART WITH fully suppressed HIV RNA counts
- •CD4 counts >400/µL inclusive at the Screening Visit.
- •Plasma levels of HIV RNA < 50 copies/mL at the Screening Visit.
排除标准
- •Applicable to ALL subjects
- •Any serious systemic disease or infection (other than HIV in PLWHA) that occurred within four weeks prior to Screening, as determined by the Investigator.
- •Patients with active bacterial or parasitic infections requiring antibiotics or antiparasitic agents will be excluded. Antibiotic or antiparasitic agents used for prophylaxis are acceptable until 7 days prior to treatment initiation.
- •Stool cultures that are positive for any pathogenic infection at screening visit.
- •Clinically significant cardiovascular disease will include:
- •History of stroke, transient ischemic attack, or myocardial infarction within 6 months prior to Screening.
- •History of or currently have New York Heart Association Class III-IV heart failure prior to Screening.
- •Female subject who is pregnant or breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive methods.
- •Subject has participated in another clinical study, involving an Investigational Product or an Investigational Device use in the past 1 month prior to commencement of this study.
- •Use of Mytesi (crofelemer) within 4 weeks of the Screening Visit Applicable to ALL HIV-negative subjects
- •Positive for Human Immunodeficiency Virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis B core antibody or hepatitis C antibodies (HepCAb).
- •Presence or history of cancer within the past five years except for adequately treated localized basal cell skin cancer or in situ uterine cervical cancer.
- •Chronic diarrhea or loose stools requiring antimotility medications including, but not limited to loperamide, diphenoxylate/atropine, tincture opium and/or octreotide within 2 weeks of the Screening Visit.
- •Applicable to ALL PLWHA subjects
- •HIV Patients with infectious diarrhea identified by either stool culture
研究组 & 干预措施
Healthy Volunteers (HIV-negative)
Drug: crofelemer delayed-release tablets, 125 mg BID x 30 days
干预措施: Crofelemer delayed-release tablets 125mg (Drug)
HIV+ Patients (Fully Suppressed, Viral Load < 50c/mL)
Drug: crofelemer delayed-release tablets, 125mg BID x 30 Days
干预措施: Crofelemer delayed-release tablets 125mg (Drug)
HIV+ Patients (Not fully suppressed viral load > 1000c/mL
Drug: crofelemer delayed-release tablets, 125mg BID x 30 Days
干预措施: Crofelemer delayed-release tablets 125mg (Drug)
结局指标
主要结局
Changes in gut microbiome
时间窗: Screening (Visit 1/Day -21) to end of Study Visit 4 (Day 60)
Stool microbiomes will be evaluated to compare the differences in the stool microbiome at Visits 2, (Day 1) Visit 3 (Day 30) and Visit 4 (Day 60) using a proprietary microbiome statistical tool (μScope) and R statistical computing and graphics software.
次要结局
- Evaluation of reduction in the number of watery BMs(From baseline (Day -7) to end of study (Day 60))
- Assessment of changes in Daily GI symptom Scale (DGIS)(From baseline (Day -7) to end of study (Day 60))