Phase2a Primaquine Dose Escalation Study
Primary Purpose
Malaria
Status
Completed
Phase
Phase 2
Locations
Mali
Study Type
Interventional
Intervention
dihydroartemisinin-piperaquine
0.125 mg/kg Primaquine
0.5 mg/kg Primaquine
0.25 mg/kg Primaquine
0.0625 mg/kg Primaquine
Sponsored by
About this trial
This is an interventional treatment trial for Malaria
Eligibility Criteria
Inclusion Criteria:
- Male
- Age >= 18 years and < 50 years
- Malaria blood thick film positive
- Presence of gametocytes on thick blood film
- Agrees to admission to study ward for 26 hours post diagnosis and available for follow up visits
- No allergies to study drugs
- Hemoglobin >= 8 g/dl
- No evidence of severe or chronic disease
- Written, informed consent
Sites / Locations
- Malaria Research and Training Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Experimental
Arm Label
dihydroartemisinin-piperaquine only
DP and 0.125 mg/kg primaquine
DP and 0.5 mg/kg primaquine
DP and 0.25 mg/kg primaquine
DP and 0.0625 mg/kg primaquine
Arm Description
dihydroartemisinin -piperaquine (DP) only
DP and single dose oral 0.125 mg/kg primaquine
DP and single dose oral 0.5 mg/kg primaquine
DP and a single dose oral 0.25 mg/kg primaquine
DP and a single dose oral 0.0625 mg/kg primaquine
Outcomes
Primary Outcome Measures
mosquito infectivity assessed through membrane feeding
Baseline, Days 1, 2, 7
Secondary Outcome Measures
gametocyte prevalence and density
Baseline, Hours 2, 6, 12, 24, Days 2, 3, 7, 14, 28
primaquine pharmacokinetics - area under the curve (AUC) of parent drug and metabolite
Hours 1, 2, 3, 4, 6, 8, 12, 24
asexual parasite prevalence and density
Baseline, Hours 2, 6, 12, 24, Days 2, 3, 7, 14, 28
safety measurements including hemoglobin and signs of hemolysis
Baseline, Days 1, 2, 3, 7, 14, 28
Full Information
NCT ID
NCT01743820
First Posted
November 26, 2012
Last Updated
January 16, 2015
Sponsor
University of California, San Francisco
Collaborators
Malaria Research and Training Center, Bamako, Mali, Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Bill and Melinda Gates Foundation, Wellcome Trust
1. Study Identification
Unique Protocol Identification Number
NCT01743820
Brief Title
Phase2a Primaquine Dose Escalation Study
Official Title
Phase 2a Dose Escalation Study of the Efficacy, Safety, and Pharmacokinetics of Low Dose Primaquine for Gametocytocidal Activity Against P. Falciparum in Sub-Saharan Africa and South East Asia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Malaria Research and Training Center, Bamako, Mali, Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Bill and Melinda Gates Foundation, Wellcome Trust
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of low single-dose primaquine for gametocidal activity against P.falciparum among adult glucose-6-phosphate dehydrogenase (G6PD)-normal malaria patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
81 (Actual)
8. Arms, Groups, and Interventions
Arm Title
dihydroartemisinin-piperaquine only
Arm Type
Active Comparator
Arm Description
dihydroartemisinin -piperaquine (DP) only
Arm Title
DP and 0.125 mg/kg primaquine
Arm Type
Experimental
Arm Description
DP and single dose oral 0.125 mg/kg primaquine
Arm Title
DP and 0.5 mg/kg primaquine
Arm Type
Experimental
Arm Description
DP and single dose oral 0.5 mg/kg primaquine
Arm Title
DP and 0.25 mg/kg primaquine
Arm Type
Experimental
Arm Description
DP and a single dose oral 0.25 mg/kg primaquine
Arm Title
DP and 0.0625 mg/kg primaquine
Arm Type
Experimental
Arm Description
DP and a single dose oral 0.0625 mg/kg primaquine
Intervention Type
Drug
Intervention Name(s)
dihydroartemisinin-piperaquine
Intervention Type
Drug
Intervention Name(s)
0.125 mg/kg Primaquine
Intervention Type
Drug
Intervention Name(s)
0.5 mg/kg Primaquine
Intervention Type
Drug
Intervention Name(s)
0.25 mg/kg Primaquine
Intervention Type
Drug
Intervention Name(s)
0.0625 mg/kg Primaquine
Primary Outcome Measure Information:
Title
mosquito infectivity assessed through membrane feeding
Description
Baseline, Days 1, 2, 7
Time Frame
7 days
Secondary Outcome Measure Information:
Title
gametocyte prevalence and density
Description
Baseline, Hours 2, 6, 12, 24, Days 2, 3, 7, 14, 28
Time Frame
28 days
Title
primaquine pharmacokinetics - area under the curve (AUC) of parent drug and metabolite
Description
Hours 1, 2, 3, 4, 6, 8, 12, 24
Time Frame
24 hours
Title
asexual parasite prevalence and density
Description
Baseline, Hours 2, 6, 12, 24, Days 2, 3, 7, 14, 28
Time Frame
28 days
Title
safety measurements including hemoglobin and signs of hemolysis
Description
Baseline, Days 1, 2, 3, 7, 14, 28
Time Frame
28 days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male
Age >= 18 years and < 50 years
Malaria blood thick film positive
Presence of gametocytes on thick blood film
Agrees to admission to study ward for 26 hours post diagnosis and available for follow up visits
No allergies to study drugs
Hemoglobin >= 8 g/dl
No evidence of severe or chronic disease
Written, informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roland Gosling, MD, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alassane Dicko, MD
Organizational Affiliation
Malaria Research and Training Centre
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
François Nosten, MD
Organizational Affiliation
Shoklo Malaria Research Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
Malaria Research and Training Centre
City
Bamako
Country
Mali
12. IPD Sharing Statement
Citations:
PubMed Identifier
21951597
Citation
Gosling RD, Okell L, Mosha J, Chandramohan D. The role of antimalarial treatment in the elimination of malaria. Clin Microbiol Infect. 2011 Nov;17(11):1617-23. doi: 10.1111/j.1469-0691.2011.03660.x. Epub 2011 Sep 26.
Results Reference
background
PubMed Identifier
17254503
Citation
Baird JK, Schwartz E, Hoffman SL. Prevention and treatment of vivax malaria. Curr Infect Dis Rep. 2007 Jan;9(1):39-46. doi: 10.1007/s11908-007-0021-4.
Results Reference
background
Citation
WHO (2011) World Malaria Report 2011. Geneva: World Health Organization.
Results Reference
background
Citation
WHO (2010) Guidelines for the treatment of malaria, Second edition. Geneva: World Health Organization
Results Reference
background
PubMed Identifier
18074034
Citation
El-Sayed B, El-Zaki SE, Babiker H, Gadalla N, Ageep T, Mansour F, Baraka O, Milligan P, Babiker A. A randomized open-label trial of artesunate- sulfadoxine-pyrimethamine with or without primaquine for elimination of sub-microscopic P. falciparum parasitaemia and gametocyte carriage in eastern Sudan. PLoS One. 2007 Dec 12;2(12):e1311. doi: 10.1371/journal.pone.0001311.
Results Reference
background
PubMed Identifier
20194698
Citation
Shekalaghe SA, ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother. 2010 May;54(5):1762-8. doi: 10.1128/AAC.01135-09. Epub 2010 Mar 1.
Results Reference
background
PubMed Identifier
26906747
Citation
Dicko A, Brown JM, Diawara H, Baber I, Mahamar A, Soumare HM, Sanogo K, Koita F, Keita S, Traore SF, Chen I, Poirot E, Hwang J, McCulloch C, Lanke K, Pett H, Niemi M, Nosten F, Bousema T, Gosling R. Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomised phase 2 trial. Lancet Infect Dis. 2016 Jun;16(6):674-684. doi: 10.1016/S1473-3099(15)00479-X. Epub 2016 Feb 20. Erratum In: Lancet Infect Dis. 2017 Jan;17(1):17.
Results Reference
derived
Learn more about this trial
Phase2a Primaquine Dose Escalation Study
We'll reach out to this number within 24 hrs