Acquired Immunodeficiency SyndromePhase 4NCT04192487
Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
A Phase 4 study testing Crofelemer delayed-release tablets 125mg in people with Acquired Immunodeficiency Syndrome and Healthy Volunteers, run by Napo Pharmaceuticals, Inc. at 3 sites in United States.
Trial summary
This study is intended to evaluate: 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)… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Acquired Immunodeficiency Syndrome, Healthy Volunteers, HIV/AIDS
- What is being tested?
- Crofelemer delayed-release tablets 125mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesUnited States
- Study dates
- 22 Oct 2019to 31 Aug 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The Research Institute
Springfield, Massachusetts, 01105
Healthcare Advocates International
Stratford, Connecticut, 06615
Orange County Research Center
Tustin, California, 92780
About this study
Official title: 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
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.
Read the detailed description
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.
- Conditions
- Acquired Immunodeficiency Syndrome, Healthy Volunteers, HIV/AIDS, HIV Diarrhea, Human Immunodeficiency Virus
- Being tested
- Crofelemer delayed-release tablets 125mg
- Keywords
- Combination Antiretroviral Therapy (CART), CD4 Cell Count, Gut Microbiome, Non-Infectious Diarrhea, Diarrhea
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crofelemer delayed-release tablets 125mgDrug
Also called Mytesi delayed-release tablets 125mg
1 crofelemer delayed-release tablet twice daily at least 8 hours apart for 30 days with or without meals.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Volunteers (HIV-negative) | Experimental | Drug: crofelemer delayed-release tablets, 125 mg BID x 30 days Receives: 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 Receives: 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 Receives: Drug: Crofelemer delayed-release tablets 125mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Defined as a score of 6 or 7 on the Bristol Stool Scale
Measured: From baseline (Day -7) to end of study (Day 60)
Assessment of changes in Daily GI symptom Scale (DGIS)
Daily presence or absence of abdominal pain, bloating, gurgling, flatulence, and bowel incontinence
Measured: From baseline (Day -7) to end of study (Day 60)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start22 Oct 2019
- Primary completion31 Aug 2021
- Study completion31 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acquired Immunodeficiency SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Napo Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Smith, MD, Principal investigator, Integrium Clinical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04192487
- Sponsor's protocol ID
- NP 303-103
- Status last verified
- Nov 2020
- First submitted
- 4 Nov 2019
- Last updated
- 22 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 17450031Cello 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.
PubMed 19457421MacArthur 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.
PubMed 22700829Tradtrantip 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.
PubMed 19808995Macarthur 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.
PubMed 24334179
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04192487
- Acronym / sponsor ID
- NP 303-103
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Napo Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 22 Oct 2019 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 31 Aug 2021 (actual)
- First posted
- 10 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteers (HIV-negative) | Experimental | Drug: Crofelemer delayed-release tablets 125mgDrug: crofelemer delayed-release tablets, 125 mg BID x 30 days |
| HIV+ Patients (Fully Suppressed, Viral Load < 50c/mL) | Experimental | Drug: Crofelemer delayed-release tablets 125mgDrug: crofelemer delayed-release tablets, 125mg BID x 30 Days |
| HIV+ Patients (Not fully suppressed viral load > 1000c/mL | Experimental | Drug: Crofelemer delayed-release tablets 125mgDrug: crofelemer delayed-release tablets, 125mg BID x 30 Days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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).
Key exclusion criteria (15 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Crofelemer delayed-release tablets 125mgAlso: Mytesi delayed-release tablets 125mg1 crofelemer delayed-release tablet twice daily at least 8 hours apart for 30 days with or without meals. | Drug | HIV+ Patients (Fully Suppressed, Viral Load < 50c/mL), HIV+ Patients (Not fully suppressed viral load > 1000c/mL, Healthy Volunteers (HIV-negative) |
Primary outcome
Changes in gut microbiome
Time frame: 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.
2 secondary outcomes
Evaluation of reduction in the number of watery BMs
Time frame: From baseline (Day -7) to end of study (Day 60)
Assessment of changes in Daily GI symptom Scale (DGIS)
Time frame: From baseline (Day -7) to end of study (Day 60)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2021.
- Background: PubMed 17450031Siddiqui 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.
- Background: PubMed 19457421Cello 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.
- Background: PubMed 22700829MacArthur 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.
- Background: PubMed 19808995Tradtrantip 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.
- Background: PubMed 24334179Macarthur 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Smith, MD principal investigator
Integrium Clinical Research
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Crofelemer delayed-release tablets 125mg in people with Acquired Immunodeficiency Syndrome and Healthy Volunteers, run by Napo Pharmaceuticals, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in gut microbiome (time frame: Screening (Visit 1/Day -21) to end of Study Visit 4 (Day 60)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04192487, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2021.