Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea

NCT04192487 | Completed Phase 4 FDA Drug

• 1 other identifier: NP 303-103
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

This study is intended to evaluate:

1. 1.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.
2. 2.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.

Conditions

Acquired Immunodeficiency Syndrome; Healthy Volunteers; HIV/AIDS; HIV Diarrhea; Human Immunodeficiency Virus

Keywords

Combination Antiretroviral Therapy (CART); CD4 Cell Count; Gut Microbiome; Non-Infectious Diarrhea; Diarrhea

Outcome Measures

Primary Outcomes (1)

• Changes in gut microbiome

  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.

  Screening (Visit 1/Day -21) to end of Study Visit 4 (Day 60)

Secondary Outcomes (2)

• 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)

Study Arms (3)

Healthy Volunteers (HIV-negative)

EXPERIMENTAL

Drug: crofelemer delayed-release tablets, 125 mg BID x 30 days

Drug: Crofelemer delayed-release tablets 125mg

HIV+ Patients (Fully Suppressed, Viral Load < 50c/mL)

EXPERIMENTAL

Drug: crofelemer delayed-release tablets, 125mg BID x 30 Days

Drug: Crofelemer delayed-release tablets 125mg

HIV+ Patients (Not fully suppressed viral load > 1000c/mL

EXPERIMENTAL

Drug: crofelemer delayed-release tablets, 125mg BID x 30 Days

Drug: Crofelemer delayed-release tablets 125mg

Interventions

Crofelemer delayed-release tablets 125mg DRUG

1 crofelemer delayed-release tablet twice daily at least 8 hours apart for 30 days with or without meals.

Also known as: Mytesi delayed-release tablets 125mg

HIV+ Patients (Fully Suppressed, Viral Load < 50c/mL); HIV+ Patients (Not fully suppressed viral load > 1000c/mL; Healthy Volunteers (HIV-negative)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 2.
• 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).
• 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.
• CD4 counts \>200/µL at the Screening Visit.
• Plasma levels of HIV RNA greater than 1,000 copies/mL at the Screening Visit.
• CD4 counts \>400/µL inclusive at the Screening Visit.
• Plasma levels of HIV RNA \< 50 copies/mL at the Screening Visit.

You may not qualify if:

• 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

Sponsors & Collaborators

• Napo Pharmaceuticals, Inc.: lead

Study Sites (3)

Orange County Research Center

Tustin, California, 92780, United States

Location

Healthcare Advocates International

Stratford, Connecticut, 06615, United States

Location

The Research Institute

Springfield, Massachusetts, 01105, United States

Location

Related Publications (5)

• Siddiqui U, Bini EJ, Chandarana K, Leong J, Ramsetty S, Schiliro D, Poles M. Prevalence and impact of diarrhea on health-related quality of life in HIV-infected patients in the era of highly active antiretroviral therapy. J Clin Gastroenterol. 2007 May-Jun;41(5):484-90. doi: 10.1097/01.mcg.0000225694.46874.fc.

  PMID: 17450031 BACKGROUND

• Cello JP, Day LW. Idiopathic AIDS enteropathy and treatment of gastrointestinal opportunistic pathogens. Gastroenterology. 2009 May;136(6):1952-65. doi: 10.1053/j.gastro.2008.12.073. Epub 2009 May 7.

  PMID: 19457421 BACKGROUND

• MacArthur RD, DuPont HL. Etiology and pharmacologic management of noninfectious diarrhea in HIV-infected individuals in the highly active antiretroviral therapy era. Clin Infect Dis. 2012 Sep;55(6):860-7. doi: 10.1093/cid/cis544. Epub 2012 Jun 14.

  PMID: 22700829 BACKGROUND

• Tradtrantip L, Namkung W, Verkman AS. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6.

  PMID: 19808995 BACKGROUND

• Macarthur RD, Hawkins TN, Brown SJ, Lamarca A, Clay PG, Barrett AC, Bortey E, Paterson C, Golden PL, Forbes WP. Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study. HIV Clin Trials. 2013 Nov-Dec;14(6):261-73. doi: 10.1310/hct1406-261.

  PMID: 24334179 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Diarrhea

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• David Smith, MD

  Integrium Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: December 10, 2019
• Study Start: October 22, 2019
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: October 22, 2021

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)