Evaluation of the Safety of Primaquine in Combination With Dihydroartemisinin-piperaquine in G6PD Deficient Males in The Gambia

NCT02654730 | Terminated Phase 2 DMC

• 1 other identifier: SAFEPRIM-II
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the tolerability and safety of increasing doses of primaquine in combination with dihydroartemisinin-piperaquine in G6PD deficient males.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Haemoglobin concentration relative to baseline value as measured by HemoCue

  28 days

Secondary Outcomes (9)

• Haematology abnormalities during follow-up: haptoglobin concentration measured in venous blood samples by full blood count analysis

  28 days

• Biochemistry abnormalities during follow-up: bilirubin concentration

  28 days

• Biochemistry abnormalities during follow-up: lactate dehydrogenase

  28 days

• Biochemistry abnormalities during follow-up: creatinine

  28 days

• Biochemistry abnormalities during follow-up: potassium

  28 days

Study Arms (5)

G6PD deficient 0.25 mg/kg PQ + DHAP

EXPERIMENTAL

Drug: Dihydroartemisinin-piperaquine (DHAP) + 0.25 mg/kg primaquine administered to G6PD deficient

G6PD deficient 0.4 mg/kg PQ + DHAP

EXPERIMENTAL

Drug: Dihydroartemisinin-piperaquine (DHAP) + 0.4 mg/kg primaquine administered to G6PD deficient

G6PD deficient DHAP only

ACTIVE COMPARATOR

Drug: Dihydroartemisinin-piperaquine (DHAP) administered to G6PD deficient

G6PD normal 0.25 mg/kg PQ + DHAP

ACTIVE COMPARATOR

Drug: Dihydroartemisinin-piperaquine (DHAP) + 0.25 mg/kg primaquine administered to G6PD normal

G6PD normal 0.4 mg/kg PQ + DHAP

ACTIVE COMPARATOR

Drug: Dihydroartemisinin-piperaquine (DHAP) + 0.4 mg/kg primaquine administered to G6PD normal

Interventions

Dihydroartemisinin-piperaquine (DHAP) administered to G6PD deficient DRUG

G6PD deficient participants will be treated with dihydroartemisinin-piperaquine (Eurartesim®; Sigma Tau) administered as 3 tablets (40mg PPQ, 320mg DHA) in a once daily regimen for three days

Also known as: Eurartesim

G6PD deficient DHAP only

Dihydroartemisinin-piperaquine (DHAP) + 0.25 mg/kg primaquine administered to G6PD deficient DRUG

G6PD deficient participants will be treated with dihydroartemisinin-piperaquine (Eurartesim®; Sigma Tau) administered as 3 tablets (40mg PPQ, 320mg DHA) in a once daily regimen for three days in combination with a single dose of 0.25mg/kg of primaquine on the first day of DHAP treatment.

G6PD deficient 0.25 mg/kg PQ + DHAP

Dihydroartemisinin-piperaquine (DHAP) + 0.4 mg/kg primaquine administered to G6PD deficient DRUG

G6PD deficient participants will be treated with dihydroartemisinin-piperaquine (Eurartesim®; Sigma Tau) administered as 3 tablets (40mg PPQ, 320mg DHA) in a once daily regimen for three days in combination with a single dose of 0.4mg/kg of primaquine on the first day of DHAP treatment.

G6PD deficient 0.4 mg/kg PQ + DHAP

Dihydroartemisinin-piperaquine (DHAP) + 0.25 mg/kg primaquine administered to G6PD normal DRUG

G6PD normal participants will be treated with dihydroartemisinin-piperaquine (Eurartesim®; Sigma Tau) administered as 3 tablets (40mg PPQ, 320mg DHA) in a once daily regimen for three days in combination with a single dose of 0.25mg/kg of primaquine on the first day of DHAP treatment.

G6PD normal 0.25 mg/kg PQ + DHAP

Dihydroartemisinin-piperaquine (DHAP) + 0.4 mg/kg primaquine administered to G6PD normal DRUG

G6PD normal participants will be treated with dihydroartemisinin-piperaquine (Eurartesim®; Sigma Tau) administered as 3 tablets (40mg PPQ, 320mg DHA) in a once daily regimen for three days in combination with a single dose of 0.4mg/kg of primaquine on the first day of DHAP treatment.

G6PD normal 0.4 mg/kg PQ + DHAP

Eligibility Criteria

• Age: 10 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• G6PD deficiency by fluorescent Spot test (for intervention groups and control group receiving DHA-PPQ only (N=50)
• G6PD normal activity by fluorescent Spot test for control groups (N=20)
• Informed consent by participant or caregiver (an assent is required for those 12-17 years)

You may not qualify if:

• Enrolled in another clinical trial
• Fever: temperature \>37.5°C (axillary) or history of fever in the last 24 hours
• Evidence of severe illness or active infection other than malaria
• Known allergy to study medications
• Hb \<11 g/dL
• Antimalarials taken within the last 2 weeks
• PQ taken within the last 4 weeks and blood transfusion within the last 90 days
• Current use of tuberculosis or anti-retroviral medication, sulphonamides, dapsone, nitrofurantoin, nalidixic acid, ciprofloxacin, methylene blue, toluidine blue, phenazopyridine and co-trimoxazole.
• History of severe chronic illness

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Medical Research Council Unit, The Gambia: collaborator

Study Sites (1)

Medical Research Council Laboratories

Fajara, The Gambia

Location

Related Publications (2)

• Eziefula AC, Pett H, Grignard L, Opus S, Kiggundu M, Kamya MR, Yeung S, Staedke SG, Bousema T, Drakeley C. Glucose-6-phosphate dehydrogenase status and risk of hemolysis in Plasmodium falciparum-infected African children receiving single-dose primaquine. Antimicrob Agents Chemother. 2014 Aug;58(8):4971-3. doi: 10.1128/AAC.02889-14. Epub 2014 Jun 9.

  PMID: 24913169 BACKGROUND

• Bastiaens GJH, Tiono AB, Okebe J, Pett HE, Coulibaly SA, Goncalves BP, Affara M, Ouedraogo A, Bougouma EC, Sanou GS, Nebie I, Bradley J, Lanke KHW, Niemi M, Sirima SB, d'Alessandro U, Bousema T, Drakeley C. Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: Two open-label, randomized, safety trials. PLoS One. 2018 Jan 11;13(1):e0190272. doi: 10.1371/journal.pone.0190272. eCollection 2018.

  PMID: 29324864 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2016
• First Posted: January 13, 2016
• Study Start: December 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 9, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)