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

Wuchereria Bancrofti Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02845713
• Other study ID #: 03-16-09
• Status: Completed
• Phase: Phase 1
• Start date: April 17, 2016
• Est. completion date: June 4, 2016

Study information

• Verified date: April 2019
• Source: University Hospitals Cleveland Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: June 4, 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Filariasis
• Infection
• Wuchereria Bancrofti Infection

Intervention

Drug:
• Ivermectin, Diethylcarbamazine Albendazole (IDA)
To evaluate the safety and tolerability of triple drug therapy (a single dose of ALB, IVM and DEC)

Locations

Country	Name	City	State
Côte D'Ivoire	Agboville District Hospital	Agbobille

Sponsors (2)

Lead Sponsor	Collaborator
University Hospitals Cleveland Medical Center	Washington University School of Medicine

Country where clinical trial is conducted

Côte D'Ivoire, 

References & Publications (12)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Geary TG. Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol. 2005 Nov;21(11):530-2. Epub 2005 Aug 26. Review. — View 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. — View 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. Review. — View Citation

Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002 Dec;15(6):599-608. Review. — View Citation

Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-32. Review. — View 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. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Drug Levels	Five mil-liters of blood will be taken to test drug levels	up to 12 hours
Secondary	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.	up to 1 year
Secondary	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.	up to 7 days
Secondary	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.	up to 1 year
Secondary	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.	up to 7 days
Secondary	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.	up to 7 days
Secondary	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.	up to 7 days