Safety and Effectiveness of 3 Doses of Crofelemer Compared to Placebo in the Treatment of HIV Associated Diarrhea - Full Text View

Sponsored by:	Napo Pharmaceuticals, Inc.
Information provided by:	Napo Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00547898

Purpose

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.

Condition	Intervention	Phase
Diarrhea HIV Infections Gastrointestinal Disease	Drug: crofelemer	Phase III

MedlinePlus related topics: AIDS Diarrhea

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	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

Further study details as provided by Napo Pharmaceuticals, Inc.:

Primary Outcome Measures:

The primary objective is to determine the proportion of HIV-positive subjects experiencing relief of diarrhea with crofelemer compared to placebo during the placebo-controlled treatment phase. [ Time Frame: 31 days ]

Secondary Outcome Measures:

To evaluate the effects of crofelemer vs. placebo on: [ Time Frame: 6 months ]
Number of bowel movements per day [ Time Frame: 6 months ]
Number of watery bowel movements per day [ Time Frame: 6 months ]
Symptom frequency [ Time Frame: 6 months ]
Symptom severity [ Time Frame: 6 months ]
Daily stool consistency score [ Time Frame: 6 months ]
Safety and tolerability of [ Time Frame: 6 months ]

Estimated Enrollment:	350
Study Start Date:	October 2007
Estimated Study Completion Date:	March 2009

Intervention Details:

crofelemer 125 mg by mouth twice daily

crofelemer 250 mg by mouth twice daily

crofelemer 500 mg by mouth twice daily or

placebo by mouth twice daily

Detailed Description:

The purpose of this study is to test the efficacy and safety of crofelemer while treating patients with HIV-associated diarrhea. This study has two stages. The first 200 patients into the study will enroll into Stage 1. In Stage 1, three doses of crofelemer will be compared to placebo. In Stage 1, study participants are randomly assigned to 1 of 4 groups:

crofelemer 125 mg by mouth twice a day,
crofelemer 250 mg by mouth twice a day,
crofelemer 500 mg by mouth twice a day, or
placebo by mouth twice a day.

After Stage 1 is completed, the dose of crofelemer that appears to work best and /or is better tolerated than the others will be selected to be used exclusively in Stage 2.

The next 150 subjects that enroll will start in Stage 2 and will be randomly assigned to receive either the selected dose of crofelemer or placebo. In Stage 2, participants will have a 50:50 chance of receiving either crofelemer or placebo.

Study Requirements:

Each Stage consists of a 10-day screening period, a 31-day study phase (double-blind, placebo-controlled) and a 5-month extension phase (placebo-free, all participants in this stage will receive crofelemer for up to 5 months).

Daily phone diary describing diarrhea symptoms will be required throughout the 28 weeks of study participation.

Maximum duration of study participation is approximately 28 weeks.

Study Phase: Phase III

Study Type: Interventional, Supportive care

Study Design: Multi-center, Double-blind, Placebo-controlled, Two-stage Adaptive design

Primary Outcome Measures:

The primary objective is to determine the proportion of HIV-positive subjects experiencing relief of diarrhea with crofelemer compared to placebo during the placebo-controlled treatment phase.

Secondary Outcome Measure(s):

To evaluate the effects of crofelemer vs. placebo on:

Number of bowel movements per day (frequency)
Number of watery bowel movements per day
Symptom frequency (urgency, fecal incontinence)
Symptom severity (abdominal pain or discomfort)
Daily stool consistency score
Safety and tolerability of crofelemer therapy, including the need for anti-diarrhea medication

Condition: HIV Associated Diarrhea

Intervention: Antidiarrheal Medication; crofelemer

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Written informed consent
Male or female, age ≥ 18 years
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
Negative pregnancy test if female of child-bearing potential
Agreement to use a method of contraception throughout the study that is deemed acceptable by the investigator
Colonoscopy within the past 5 years if ≥ 50 years of age.
Willingness to withdraw all antidiarrheal and certain other medications for the first 6 weeks of the study
Willingness to comply with the requirements of the study, including regular study visits and daily telephone diary

Exclusion Criteria:

Pregnancy or breast-feeding
Current or past gastrointestinal (GI) medical or surgical conditions including but not limited to the following: GI surgery, history of inflammatory gastrointestinal diseases known to be associated with diarrhea, tube feedings, bowel obstruction or stricture, positive gastrointestinal biopsy or stool test result in the past 4 months for certain pathologic organisms
Bright red blood per rectum judged not to be of an anal (hemorrhoid, fissure) origin.
Evidence on prior colonoscopy or upper endoscopy of colitis, enteritis, infection (HIV-associated or otherwise), or neoplasm, other than benign polyps.
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
Oral temperature greater than 100.4 oF or unintentional weight loss of 11 lbs. or greater during the prior 2 months
Any of the following laboratory abnormalities:
CD4 counts < 100 cells/mm3
Serum creatinine ≥ 3.0 mg/dL
Alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin ≥ 3 times the upper limit of normal
Hemoglobin (Hgb) < 8.0 mg/dL
Absolute neutrophil count or lymphocyte count ≤ 500 cells/µL
Presence or history of cancer of any type (except treated basal cell carcinoma), including Kaposi's sarcoma or other HIV-associated neoplasm, within the last 5 years
Use of any investigational drug, with the exception of a drug administered through an expanded access program that is registered with the U.S. Food and Drug Administration within 4 weeks of receiving study drug
Active drug or alcohol abuse, or other medical conditions that in the opinion of the investigator may interfere with the subject's ability to comply with this protocol, or places the subject at increased risk.
Planned in-patient hospitalization during the study
Previous randomization into this study, or into any other study in which crofelemer (i.e., Provir®, SP-303)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00547898

Contacts

Contact: Jill M Leonard, RN, BSN	513-345-1837	leonard.jillm@kendle.com
Contact: Mark McDougal	919-447-3411	mark.mcdougal@salix.com

Show 55 Study Locations

Sponsors and Collaborators

Napo Pharmaceuticals, Inc.

Investigators

Study Director:

M. Scott Harris, MD

Napo Pharmaceuticals

More Information

Additional Information:

Study information and patient self screener This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	NP303-101
Study First Received:	October 21, 2007
Last Updated:	May 1, 2009
ClinicalTrials.gov Identifier:	NCT00547898 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Napo Pharmaceuticals, Inc.:

HIV
AIDS
Diarrhea
HIV Associated Diarrhea
Treatment Experienced

Study placed in the following topic categories:

Virus Diseases
Signs and Symptoms
Sexually Transmitted Diseases, Viral
Digestive System Diseases
Diarrhea
Signs and Symptoms, Digestive

Gastrointestinal Diseases
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Diarrhea
Signs and Symptoms, Digestive
Immune System Diseases
Gastrointestinal Diseases
Acquired Immunodeficiency Syndrome
Infection

Immunologic Deficiency Syndromes
Virus Diseases
Signs and Symptoms
Digestive System Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on May 07, 2009