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

NCT ID: NCT02845713

Last Updated: 2019-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-17
• Study Completion Date: 2016-06-04

Brief Summary

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.

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.

Conditions

Wuchereria Bancrofti Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Single IDA dose W. bancrofti positive

Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) W. bancrofti infections positive

Group Type: ACTIVE_COMPARATOR

Ivermectin, Diethylcarbamazine Albendazole (IDA)

Intervention Type: DRUG

To evaluate the safety and tolerability of triple drug therapy (a single dose of ALB, IVM and DEC)

Single IDA dose W. bancrofti negative

Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) in 40 individuals who are free of W. bancrofti infection.

Group Type: ACTIVE_COMPARATOR

Ivermectin, Diethylcarbamazine Albendazole (IDA)

Intervention Type: DRUG

To evaluate the safety and tolerability of triple drug therapy (a single dose of ALB, IVM and DEC)

Interventions

Ivermectin, Diethylcarbamazine Albendazole (IDA)

To evaluate the safety and tolerability of triple drug therapy (a single dose of ALB, IVM and DEC)

Intervention Type: DRUG

Other Intervention Names

IDA

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Christopher L. King, MD, PhD

Professor of International Health, Medicine and Pathology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Agboville District Hospital

Agbobille, , Côte d’Ivoire

Countries

Côte d’Ivoire

References

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Other Identifiers

03-16-09

Identifier Type: -

Identifier Source: org_study_id