Pharmacokinetics & Pharmacodynamics of Diethylcarbamazine (DEC)+ Albendazole (ALB) + Ivermectin (IVE)
Primary Purpose
Wuchereria Bancrofti Infection
Status
Completed
Phase
Phase 1
Locations
Côte D'Ivoire
Study Type
Interventional
Intervention
Ivermectin, Diethylcarbamazine Albendazole (IDA)
Sponsored by
About this trial
This is an interventional other trial for Wuchereria Bancrofti Infection
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.
Sites / Locations
- Agboville District Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Single IDA dose W. bancrofti positive
Single IDA dose W. bancrofti negative
Arm Description
Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) W. bancrofti infections positive
Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) in 40 individuals who are free of W. bancrofti infection.
Outcomes
Primary Outcome Measures
Drug Levels
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)
Following drug administration, a review of subjective symptoms will be performed.
Impact of treatment on Hematuria and Proteinuria
Urine samples will be collected to examine the the presence and amount of blood and protein in the urine.
Number worm nests
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 +
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
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
Blood samples will be collected to examine the impact of treatment on the levels of white blood count in subjects blood.
Full Information
NCT ID
NCT02845713
First Posted
June 3, 2016
Last Updated
April 25, 2019
Sponsor
University Hospitals Cleveland Medical Center
Collaborators
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT02845713
Brief Title
Pharmacokinetics & Pharmacodynamics of Diethylcarbamazine (DEC)+ Albendazole (ALB) + Ivermectin (IVE)
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
April 17, 2016 (Actual)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 4, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospitals Cleveland Medical Center
Collaborators
Washington University School of Medicine
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wuchereria Bancrofti Infection
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single IDA dose W. bancrofti positive
Arm Type
Active Comparator
Arm Description
Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) W. bancrofti infections positive
Arm Title
Single IDA dose W. bancrofti negative
Arm Type
Active Comparator
Arm Description
Single oral dose of Ivermectin, Diethylcarbamazine Albendazole (IDA) in 40 individuals who are free of W. bancrofti infection.
Intervention Type
Drug
Intervention Name(s)
Ivermectin, Diethylcarbamazine Albendazole (IDA)
Other Intervention Name(s)
IDA
Intervention Description
To evaluate the safety and tolerability of triple drug therapy (a single dose of ALB, IVM and DEC)
Primary Outcome Measure Information:
Title
Drug Levels
Description
Five mil-liters of blood will be taken to test drug levels
Time Frame
up to 12 hours
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (aggregate)
Description
Following drug administration, a review of subjective symptoms will be performed.
Time Frame
up to 1 year
Title
Impact of treatment on Hematuria and Proteinuria
Description
Urine samples will be collected to examine the the presence and amount of blood and protein in the urine.
Time Frame
up to 7 days
Title
Number worm nests
Description
In those individuals with LF, an ultrasound examination will be performed to identify the number of adult worm nests both before treatment and after.
Time Frame
up to 1 year
Title
Impact of treatment on Liver Function +
Description
Blood samples will be collected to examine the impact of treatment on the levels of ALT, AST in the subjects blood.
Time Frame
up to 7 days
Title
Impact of treatment on Hemoglobin Levels
Description
Blood samples will be collected to examine the impact of treatment on the levels of Hemoglobin in the subjects blood.
Time Frame
up to 7 days
Title
Impact of treatment on White Blood Cells
Description
Blood samples will be collected to examine the impact of treatment on the levels of white blood count in subjects blood.
Time Frame
up to 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
Agboville District Hospital
City
Agbobille
Country
Côte D'Ivoire
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
7660449
Citation
Andrade LD, Medeiros Z, Pires ML, Pimentel A, Rocha A, Figueredo-Silva J, Coutinho A, Dreyer G. Comparative efficacy of three different diethylcarbamazine regimens in lymphatic filariasis. Trans R Soc Trop Med Hyg. 1995 May-Jun;89(3):319-21. doi: 10.1016/0035-9203(95)90561-8.
Results Reference
background
PubMed Identifier
12803872
Citation
Awadzi K, Edwards G, Duke BO, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quartey BT. The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2003 Mar;97(2):165-78. doi: 10.1179/000349803235001697.
Results Reference
background
PubMed Identifier
15324466
Citation
Awadzi K, Edwards G, Opoku NO, Ardrey AE, Favager S, Addy ET, Attah SK, Yamuah LK, Quartey BT. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2004 Sep;98(6):595-614. doi: 10.1179/000349804225021370.
Results Reference
background
PubMed Identifier
11865970
Citation
Bolla S, Boinpally RR, Poondru S, Devaraj R, Jasti BR. Pharmacokinetics of diethylcarbamazine after single oral dose at two different times of day in human subjects. J Clin Pharmacol. 2002 Mar;42(3):327-31. doi: 10.1177/00912700222011247.
Results Reference
background
PubMed Identifier
6130195
Citation
Dominguez-Vazquez A, Taylor HR, Greene BM, Ruvalcaba-Macias AM, Rivas-Alcala AR, Murphy RP, Beltran-Hernandez F. Comparison of flubendazole and diethylcarbamazine in treatment of onchocerciasis. Lancet. 1983 Jan 22;1(8317):139-43. doi: 10.1016/s0140-6736(83)92753-8.
Results Reference
background
PubMed Identifier
14993632
Citation
El Setouhy M, Ramzy RM, Ahmed ES, Kandil AM, Hussain O, Farid HA, Helmy H, Weil GJ. A randomized clinical trial comparing single- and multi-dose combination therapy with diethylcarbamazine and albendazole for treatment of bancroftian filariasis. Am J Trop Med Hyg. 2004 Feb;70(2):191-6.
Results Reference
background
PubMed Identifier
16126457
Citation
Geary TG. Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol. 2005 Nov;21(11):530-2. doi: 10.1016/j.pt.2005.08.014. Epub 2005 Aug 26.
Results Reference
background
PubMed Identifier
25411843
Citation
Hooper PJ, Chu BK, Mikhailov A, Ottesen EA, Bradley M. Assessing progress in reducing the at-risk population after 13 years of the global programme to eliminate lymphatic filariasis. PLoS Negl Trop Dis. 2014 Nov 20;8(11):e3333. doi: 10.1371/journal.pntd.0003333. eCollection 2014 Nov.
Results Reference
background
PubMed Identifier
11386684
Citation
Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-32. doi: 10.1017/s0031182000007290.
Results Reference
background
PubMed Identifier
12821837
Citation
Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002 Dec;15(6):599-608. doi: 10.1097/00001432-200212000-00008.
Results Reference
background
PubMed Identifier
19843396
Citation
Horton J. The development of albendazole for lymphatic filariasis. Ann Trop Med Parasitol. 2009 Oct;103 Suppl 1:S33-40. doi: 10.1179/000349809X12502035776595.
Results Reference
background
PubMed Identifier
11386686
Citation
Horton J, Witt C, Ottesen EA, Lazdins JK, Addiss DG, Awadzi K, Beach MJ, Belizario VY, Dunyo SK, Espinel M, Gyapong JO, Hossain M, Ismail MM, Jayakody RL, Lammie PJ, Makunde W, Richard-Lenoble D, Selve B, Shenoy RK, Simonsen PE, Wamae CN, Weerasooriya MV. An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis. Parasitology. 2000;121 Suppl:S147-60. doi: 10.1017/s0031182000007423.
Results Reference
background
PubMed Identifier
34310218
Citation
Bala V, Chhonker YS, Alshehri A, Edi C, Bjerum CM, Koudou BG, King CL, Murry DJ. Population Pharmacokinetics of Diethylcarbamazine in Patients with Lymphatic Filariasis and Healthy Individuals. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0031721. doi: 10.1128/AAC.00317-21. Epub 2021 Jul 26.
Results Reference
derived
PubMed Identifier
31107869
Citation
Edi C, Bjerum CM, Ouattara AF, Chhonker YS, Penali LK, Meite A, Koudou BG, Weil GJ, King CL, Murry DJ. Pharmacokinetics, safety, and efficacy of a single co-administered dose of diethylcarbamazine, albendazole and ivermectin in adults with and without Wuchereria bancrofti infection in Cote d'Ivoire. PLoS Negl Trop Dis. 2019 May 20;13(5):e0007325. doi: 10.1371/journal.pntd.0007325. eCollection 2019 May.
Results Reference
derived
Learn more about this trial
Pharmacokinetics & Pharmacodynamics of Diethylcarbamazine (DEC)+ Albendazole (ALB) + Ivermectin (IVE)
We'll reach out to this number within 24 hrs