Safety and Effectiveness of 3 Doses of Crofelemer Compared to Placebo in the Treatment of HIV Associated Diarrhea (ADVENT)

Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Two-Stage Study to Assess the Efficacy and Safety of 3 Doses of Crofelemer Orally Twice Daily for the Treatment of HIV-Associated Diarrhea

This is a randomized, double-blind, parallel-group, placebo-controlled, multi-center study. This study will compare an investigational new drug (crofelemer) to placebo for the control of HIV-associated diarrhea. The first stage of the study will determine the optimal dose of study drug based on safety and response to therapy and the second stage will evaluate further the effectiveness of the optimal dose.

Study Overview

• Status: Completed
• Conditions: HIV Associated Diarrhea
• Intervention / Treatment: Drug: Placebo; Drug: Crofelemer 125 mg; Drug: Crofelemer 250 mg; Drug: Crofelemer 500 mg

• Study Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00717
  • Rio Piedras, Puerto Rico, 00935
  • San Juan, Puerto Rico, 00909
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
  • Arizona
    • Phoenix, Arizona, United States, 85006
  • Arkansas
    • Little Rock, Arkansas, United States, 72207
  • California
    • Bakersfield, California, United States, 93301
    • Beverly Hills, California, United States, 90211
    • Beverly Hills, California, United States, 90210
    • Fountain Valley, California, United States, 92708
    • Long Beach, California, United States, 90813
    • Los Angeles, California, United States, 90027
    • Los Angeles, California, United States, 90015
    • Los Angeles, California, United States, 90022
    • Oakland, California, United States, 94609
    • Palm Springs, California, United States, 92262
    • San Diego, California, United States, 92120
    • San Francisco, California, United States, 94118
    • San Mateo, California, United States, 94403
  • Colorado
    • Denver, Colorado, United States, 80205
  • Florida
    • Daytona Beach, Florida, United States, 32117
    • Fort Lauderdale, Florida, United States, 33308
    • Fort Lauderdale, Florida, United States, 33316
    • Fort Lauderdale, Florida, United States, 33306
    • Fort Pierce, Florida, United States, 34982
    • Miami, Florida, United States, 33137
    • Miami, Florida, United States, 33133
    • Miami, Florida, United States, 33180
    • Miami Beach, Florida, United States, 33139
    • Orlando, Florida, United States, 32806
    • Orlando, Florida, United States, 32803
    • Tampa, Florida, United States, 33614
    • Tampa, Florida, United States, 33602
    • West Palm Beach, Florida, United States, 33401
    • Wilton Manors, Florida, United States, 33305
  • Georgia
    • Atlanta, Georgia, United States, 30309
    • Atlanta, Georgia, United States, 30318
  • Illinois
    • Chicago, Illinois, United States, 60611
    • Chicago, Illinois, United States, 60654
    • Chicago, Illinois, United States, 60607
  • Iowa
    • Iowa City, Iowa, United States, 52242
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
    • Springfield, Massachusetts, United States, 01107
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
    • Detroit, Michigan, United States, 48201
    • Detroit, Michigan, United States, 48202
  • Missouri
    • Kansas City, Missouri, United States, 64111
    • Kansas City, Missouri, United States, 64106
    • Saint Louis, Missouri, United States, 63108
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
    • Santa Fe, New Mexico, United States, 87505
  • New York
    • Bronx, New York, United States, 10461
    • Great Neck, New York, United States, 11023
    • Manhasset, New York, United States, 11030
    • Mount Vernon, New York, United States, 10550
    • New York, New York, United States, 10011
    • New York, New York, United States, 10010
    • New York, New York, United States, 10018
    • Rochester, New York, United States, 14604
  • North Carolina
    • Gastonia, North Carolina, United States, 28504
  • Ohio
    • Cincinnati, Ohio, United States, 45267
  • Oregon
    • Portland, Oregon, United States, 97210
    • Portland, Oregon, United States, 97219
  • South Carolina
    • Columbia, South Carolina, United States, 29203
  • Texas
    • Austin, Texas, United States, 78705
    • Bellaire, Texas, United States, 77401
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75243
    • Dallas, Texas, United States, 77030
    • Harlingen, Texas, United States, 78550
    • Houston, Texas, United States, 77030
    • Houston, Texas, United States, 77004
    • Houston, Texas, United States, 77074
    • Houston, Texas, United States, 77098
    • Longview, Texas, United States, 75605
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78258
  • Virginia
    • Lynchburg, Virginia, United States, 24501
    • Richmond, Virginia, United States, 23219
  • Washington
    • Seattle, Washington, United States, 98104
    • Spokane, Washington, United States, 99204

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• History of HIV-1 infection confirmed by standard serological tests
• Stable medical regimen for treatment of HIV disease and associated conditions for at least 4 weeks prior to screening
• Patient-reported history of diarrhea, defined as either persistently loose stools despite regular ADM use, or one or more watery bowel movements per day without regular ADM use, of at least 1 month duration
• Colonoscopy within the past 5 years if ≥ 50 years of age.

Exclusion Criteria:

• Pregnancy or breast-feeding
• Current or past gastrointestinal (GI) medical or surgical conditions
• Use of certain opiate pain medication within 2 weeks of screening
• Use of an antibiotic within 2 weeks prior to screening, with the exception of stable antibiotic therapy for prophylactic treatment of infection or an HIV-associated condition
• CD4 counts < 100 cells/mm3
• Previous randomization into this study, or into any other crofelemer study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Drug: Placebo; Placebo
Experimental: Crofelemer 125 mg	Drug: Crofelemer 125 mg; Crofelemer 125 mg
Experimental: Crofelemer 250 mg	Drug: Crofelemer 250 mg; Crofelemer 250 mg
Experimental: Crofelemer 500 mg	Drug: Crofelemer 500 mg; Crofelemer 500 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary Efficacy Outcome is Count of Participants With Two or Less Watery Bowel Movements Per Week During at Least Two Weeks of the Treatment Phase of the Optimal Dose of Crofelemer Compared to Placebo	31 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Relief of Diarrhea	Relief of diarrhea was defined as two or less watery bowel movements per week during at least two weeks of the treatment phase.	31 days

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): January 27, 2011
• Study Completion (Actual): July 11, 2011

Study Registration Dates

• First Submitted: October 21, 2007
• First Submitted That Met QC Criteria: October 22, 2007
• First Posted (Estimate): October 23, 2007

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Diarrhea; HIV; AIDS; HIV Associated Diarrhea
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: NP303-101