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

Sponsor

University Hospitals Cleveland Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT02845713

Collaborator

Washington University School of Medicine (Other)

Enrollment

Location

Arms

1.6

Actual Duration (Months)

41.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Wuchereria Bancrofti Infection	Drug: Ivermectin, Diethylcarbamazine Albendazole (IDA)	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

66 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Apr 17, 2016

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 4, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Drug Levels [up to 12 hours]
Five mil-liters of blood will be taken to test drug levels

Secondary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (aggregate) [up to 1 year]
Following drug administration, a review of subjective symptoms will be performed.
Impact of treatment on Hematuria and Proteinuria [up to 7 days]
Urine samples will be collected to examine the the presence and amount of blood and protein in the urine.
Number worm nests [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.
Impact of treatment on Liver Function + [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.
Impact of treatment on Hemoglobin Levels [up to 7 days]
Blood samples will be collected to examine the impact of treatment on the levels of Hemoglobin in the subjects blood.
Impact of treatment on White Blood Cells [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.