Pharmacokinetics & Pharmacodynamics of Diethylcarbamazine (DEC)+ Albendazole (ALB) + Ivermectin (IVE)

April 25, 2019 updated by: Christopher L. King, MD, PhD, University Hospitals Cleveland Medical Center

Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Single Dose Treatment With Diethylcarbamazine, Albendazole and Ivermectin in Humans With and Without Wuchereria Bancrofti Infection in Côte d'Ivoire

The study will be an open label cohort study with 2 two-treatment groups 2). Both groups will be treated with a single oral administration of Diethylcarbamazine (DEC) 6 mg/kg + Albendazole (ALB) 400 mg + Ivermectin (IVR) 200 µg/kg (IDA). One treatment group will include men and women with W. bancrofti infections (>50 Mf/ml, N=30). The other treatment group will include men and women who are free of W. bancrofti infection based on negative blood tests for both microfilariae (Mf) and circulating filarial antigen (N=30). Active follow-up for adverse events (AE) will be for 72hrs and passive follow-up for 7 days following treatment.

Participants will be followed again at 1 year to evaluate treatment efficacy. Individuals with severe AEs (grade 3 or higher) will be transported to the Agboville District Hospital and cared for by the hospital staff. Based on treatment of over 100 Lymphatic filariasis (LF) infected individuals any AEs develop within the first 72 hours following treatment and uncommonly up to 7 days post-treatment.

All individuals will be admitted to a single health center or hospital in Côte d'Ivoire.

Subjects will be monitored for 72-hours after treatment for safety and to facilitate sampling for drug analyses and safety tests. Participants will undergo clinical monitoring every 6 hours to evaluate potential adverse effects of Ivermectin + Diethylcarbamazine + Albendazole (IDA) treatment. Participants will also be monitored for hematologic, or biochemical abnormalities during the period of observation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study will be an open label cohort study with 2 two-treatment groups. Both groups will be treated with a single oral administration of DEC 6 mg/kg + ALB 400 mg + IVR 200 µg/kg (IDA). One treatment group will include men and women with W. bancrofti infections (>50 Mf/ml, N=30). The other treatment group will include men and women who are free of W. bancrofti infection based on negative blood tests for both microfilariae and circulating filarial antigen (N=30). Active follow-up for adverse events (AE) will be for 72 hours and passive follow-up for 7 days following treatment.

Participants will be followed again at 1 year to evaluate treatment efficacy. Individuals with severe AEs (grade 3 or higher) will be transported to the Agboville District Hospital and cared for by the hospital staff. Based on treatment of over 100 LF infected individuals any AEs develop within the first 72 hours following treatment and uncommonly up to 7 days post-treatment.

All individuals will be admitted to a single health center or hospital in Côte d'Ivoire.

Subjects will be monitored for 72-hours after treatment for safety and to facilitate sampling for drug analyses and safety tests. Participants will undergo clinical monitoring every 6 hours to evaluate potential adverse effects of IDA treatment. Participants will also be monitored for hematologic, or biochemical abnormalities during the period of observation.

At enrollment all subjects will be otherwise healthy adult men and women (≥18-65 years of age). All individuals will be assessed for the presence and burden of geohelminth infections, parasitic worms of the gastrointestinal tract such as hookworm, Trichuris trichiuria and Ascaris lumbricoides. This is important because two of the drugs in the combination (ALB and IVM) are active against geohelminths. Individuals with heavy geohelminth burdens may experience adverse reactions because of rapid killing of their intestinal parasites.

Study Type

Interventional

Enrollment (Actual)

66

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Côte D'Ivoire
      • Agbobille, Côte D'Ivoire
        • Agboville District Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willingness to provide informed consent to participation in the study

    • Male or female 18-65 years of age
    • Peripheral blood microfilaremia levels >50 microfilaria/ml (treatment group 1)
    • No evidence of filarial infection by Mf and Circulating filarial antigen (CFA) testing (treatment group 2)
    • No history of taking anti-filarial medications in past 2 years

Exclusion Criteria:

Known chronic illness, e.g. tuberculosis, diabetes, renal insufficiency

  • Anemia (Hb <7 g/dl) by HemaCue
  • Not willing or able to give informed consent for the study
  • Onchocerciasis rapid test (Ov16) and/or skin snip positive for onchocerciasis
  • Permanent disability that prevents or impedes study participation and/or comprehension Pregnancy. Women will be tested with a rapid urine test for beta human chorionic gonadotropin (β-HCG)
  • Biochemical abnormalities as indicated by liver function tests, and/or creatinine >1.5 times above upper limit of the normal range.
  • Receiving any routine medications that may interfere with test drug metabolism that cannot be stopped one week prior to onset of study
  • Evidence of urinary tract infection as indicated by an active urinary sediment (>6- 8 pus/neutrophil cells per field) or 3+ nitrate on dipstick. Individuals without a gross active sediment 1 or 2 plus nitrate or with 1 + protein will not be excluded. Similarly individuals with 1+ haemoglobin on dipstick or trace amount of blood in the will not be excluded.
  • Lactose and/or gluten intolerance.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Single IDA dose W. bancrofti positive
Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) W. bancrofti infections positive
Drug: Ivermectin, Diethylcarbamazine Albendazole (IDA)
To evaluate the safety and tolerability of triple drug therapy (a single dose of ALB, IVM and DEC)
Other Names:
  • IDA
Active Comparator: Single IDA dose W. bancrofti negative
Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) in 40 individuals who are free of W. bancrofti infection.
Drug: Ivermectin, Diethylcarbamazine Albendazole (IDA)
To evaluate the safety and tolerability of triple drug therapy (a single dose of ALB, IVM and DEC)
Other Names:
  • IDA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Drug Levels
Time Frame: up to 12 hours
Five mil-liters of blood will be taken to test drug levels
up to 12 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (aggregate)
Time Frame: up to 1 year
Following drug administration, a review of subjective symptoms will be performed.
up to 1 year
Impact of treatment on Hematuria and Proteinuria
Time Frame: up to 7 days
Urine samples will be collected to examine the the presence and amount of blood and protein in the urine.
up to 7 days
Number worm nests
Time Frame: up to 1 year
In those individuals with LF, an ultrasound examination will be performed to identify the number of adult worm nests both before treatment and after.
up to 1 year
Impact of treatment on Liver Function +
Time Frame: up to 7 days
Blood samples will be collected to examine the impact of treatment on the levels of ALT, AST in the subjects blood.
up to 7 days
Impact of treatment on Hemoglobin Levels
Time Frame: up to 7 days
Blood samples will be collected to examine the impact of treatment on the levels of Hemoglobin in the subjects blood.
up to 7 days
Impact of treatment on White Blood Cells
Time Frame: up to 7 days
Blood samples will be collected to examine the impact of treatment on the levels of white blood count in subjects blood.
up to 7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospitals Cleveland Medical Center

Collaborators

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2016

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

June 4, 2016

Study Registration Dates

First Submitted

June 3, 2016

First Submitted That Met QC Criteria

July 22, 2016

First Posted (Estimate)

July 27, 2016

Study Record Updates

Last Update Posted (Actual)

April 26, 2019

Last Update Submitted That Met QC Criteria

April 25, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03-16-09

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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