Antimalarial Drug Resistance With Assessment of Transmission Blocking Activity

NCT01849640 | Suspended DMC

• 2 other identifiers: WRAIR#1877HRPO Log Number A-17145
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. On the last day of DP therapy, volunteers will be randomized to receive either a single 45 mg dose of primaquine (PQ) or DP treatment only (no primaquine).

Conditions

Uncomplicated Plasmodium Falciparum Malaria

Keywords

Malaria; Drug resistance; DHA-piperaquine; Cambodia; Transmission Blocking

Outcome Measures

Primary Outcomes (1)

• Clinical efficacy of DP

  Efficacy rates at 42 days (with 95% confidence intervals) for DP with and without single dose primaquine for uncomplicated P. falciparum diagnosed by positive PCR-corrected malaria microscopy.

  3 years

Secondary Outcomes (1)

• Efficacy of Primaquine to treat sexual stage gametocyte infection and prevent transmission of P. falciparum gametocytes to mosquitoes.

  3 years

Study Arms (2)

DHA-piperaquine with Primaquine

ACTIVE COMPARATOR

3-day treatment course of DHA-piperaquine with 45mg single dose primaquine

Drug: DHA-piperaquine and Primaquine

DHA-piperaquine without Primaquine

ACTIVE COMPARATOR

3-day treatment course of DHA-piperaquine

Drug: DHA-piperaquine and Primaquine

Interventions

DHA-piperaquine and Primaquine DRUG

Subject will be enrolled in open label fashion to a 3-day treatment course of DHA-piperaquine (DP) by directly observed therapy (DOT, all patients will receive a total of 9 tablets containing 40mg DHA and 320mg of piperaquine in divided doses at 0, 24 and 48 hours (3 tablets once per day) for the 3 day course. At completion of DP treatment volunteers will be randomized in an open label fashion to receive a single 45 mg dose of primaquine or no therapy.

DHA-piperaquine with Primaquine; DHA-piperaquine without Primaquine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteer with uncomplicated P. falciparum malaria (volunteers with mixed P. falciparum and P. vivax infections may be enrolled), 18-65 years of age
• Baseline asexual parasite density between 1,000-200,000 parasites/uL
• Able to provide informed consent
• Available and agree to follow-up for anticipated study duration including 3 day treatment course at the MTF and weekly follow-up for the 42-day period
• Authorized by local commander to participate if active duty military

You may not qualify if:

• Allergic reaction or contraindication to DHA, piperaquine or primaquine
• Significant acute comorbidity requiring urgent medical intervention
• Signs/symptoms and parasitological confirmation of severe malaria
• Use of any anti-malarial within the past 14 days.
• Class I or II G6PD deficiency (defined as severe) as determined at screening
• Pregnant or lactating female, or female of childbearing age, up to 50 years of age, who does not agree to use an acceptable form of contraception during the study
• Clinically significant abnormal EKG, including a QTcF interval \> 500 ms at enrollment.
• Known or suspected concomitant use of QTc prolonging medications.
• Judged by the investigator to be otherwise unsuitable for study participation

Sponsors & Collaborators

• David Saunders: lead
• National Centre for Parasitology, Entomology and Malaria Control, Cambodia: collaborator
• Royal Cambodian Armed Forces: collaborator
• US Department of Defense Armed Forces Health Surveillance Center: collaborator

Study Sites (1)

Anlong Veng Referral Hospital

Anlong Veaeng, Oddormean Chey, Cambodia

Location

Related Publications (3)

• Saunders DL, Vanachayangkul P, Lon C; U.S. Army Military Malaria Research Program; National Center for Parasitology, Entomology, and Malaria Control (CNM); Royal Cambodian Armed Forces. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med. 2014 Jul 31;371(5):484-5. doi: 10.1056/NEJMc1403007. No abstract available.

  PMID: 25075853 BACKGROUND

• Spring MD, Lin JT, Manning JE, Vanachayangkul P, Somethy S, Bun R, Se Y, Chann S, Ittiverakul M, Sia-ngam P, Kuntawunginn W, Arsanok M, Buathong N, Chaorattanakawee S, Gosi P, Ta-aksorn W, Chanarat N, Sundrakes S, Kong N, Heng TK, Nou S, Teja-isavadharm P, Pichyangkul S, Phann ST, Balasubramanian S, Juliano JJ, Meshnick SR, Chour CM, Prom S, Lanteri CA, Lon C, Saunders DL. Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis. 2015 Jun;15(6):683-91. doi: 10.1016/S1473-3099(15)70049-6. Epub 2015 Apr 12.

  PMID: 25877962 RESULT

• Vanachayangkul P, Lon C, Spring M, Sok S, Ta-Aksorn W, Kodchakorn C, Pann ST, Chann S, Ittiverakul M, Sriwichai S, Buathong N, Kuntawunginn W, So M, Youdaline T, Milner E, Wojnarski M, Lanteri C, Manning J, Prom S, Haigney M, Cantilena L, Saunders D. Piperaquine Population Pharmacokinetics and Cardiac Safety in Cambodia. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02000-16. doi: 10.1128/AAC.02000-16. Print 2017 May.

  PMID: 28193647 DERIVED

Related Links

• Interim Results

MeSH Terms

Conditions

Malaria

Interventions

Primaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David Saunders, MD, MPH

  Dept. of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (AFRIMS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: David Saunders, LTC, MC, USA

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: May 8, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: June 1, 2016
• Last Updated: July 15, 2015

Record last verified: 2015-07

Locations

CA (1)