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

NCT02845713 | Completed Phase 1 DMC

• 1 other identifier: 03-16-09
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Wuchereria Bancrofti Infection

Outcome Measures

Primary Outcomes (1)

• Drug Levels

  Five mil-liters of blood will be taken to test drug levels

  up to 12 hours

Secondary Outcomes (6)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (aggregate)

  up to 1 year

• Impact of treatment on Hematuria and Proteinuria

  up to 7 days

• Number worm nests

  up to 1 year

• Impact of treatment on Liver Function +

  up to 7 days

• Impact of treatment on Hemoglobin Levels

  up to 7 days

Study Arms (2)

Single IDA dose W. bancrofti positive

ACTIVE COMPARATOR

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

Drug: Ivermectin, Diethylcarbamazine Albendazole (IDA)

Single IDA dose W. bancrofti negative

ACTIVE COMPARATOR

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

Drug: Ivermectin, Diethylcarbamazine Albendazole (IDA)

Interventions

Ivermectin, Diethylcarbamazine Albendazole (IDA) DRUG

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

Also known as: IDA

Single IDA dose W. bancrofti negative; Single IDA dose W. bancrofti positive

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Agboville District Hospital

Agbobille, Côte d’Ivoire

Location

Related Publications (15)

• 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.

  PMID: 7660449 BACKGROUND

• 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.

  PMID: 12803872 BACKGROUND

• 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.

  PMID: 15324466 BACKGROUND

• 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.

  PMID: 11865970 BACKGROUND

• 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.

  PMID: 6130195 BACKGROUND

• 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.

  PMID: 14993632 BACKGROUND

• 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.

  PMID: 16126457 BACKGROUND

• 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.

  PMID: 25411843 BACKGROUND

• Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-32. doi: 10.1017/s0031182000007290.

  PMID: 11386684 BACKGROUND

• 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.

  PMID: 12821837 BACKGROUND

• Horton J. The development of albendazole for lymphatic filariasis. Ann Trop Med Parasitol. 2009 Oct;103 Suppl 1:S33-40. doi: 10.1179/000349809X12502035776595.

  PMID: 19843396 BACKGROUND

• 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.

  PMID: 11386686 BACKGROUND

• Alshehri A, Chhonker YS, Bala V, Edi C, Bjerum CM, Koudou BG, John LN, Mitja O, Marks M, King CL, Murry DJ. Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis. PLoS Negl Trop Dis. 2023 Jun 1;17(6):e0011319. doi: 10.1371/journal.pntd.0011319. eCollection 2023 Jun.

  PMID: 37262040 DERIVED

• 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.

  PMID: 34310218 DERIVED

• 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.

  PMID: 31107869 DERIVED

MeSH Terms

Conditions

Elephantiasis, Filarial

Interventions

Ivermectin

Condition Hierarchy (Ancestors)

Filariasis; Spirurida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Lymphedema; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of International Health, Medicine and Pathology

Study Record Dates

• First Submitted: June 3, 2016
• First Posted: July 27, 2016
• Study Start: April 17, 2016
• Primary Completion: June 1, 2016
• Study Completion: June 4, 2016
• Last Updated: April 26, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share

Locations

CÔ (1)