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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

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.

Detailed Summary:

In the current study the investigators aim to assess safety of PQ, in particular the risk of acute haemolysis, when given together with dihydroartemisinin-piperaquine (DHAP) in G6PD deficient individuals. Forty male participants with haemoglobin levels (≥11g/dL), reduced G6PD enzyme function, and aged ≥10years will be sequentially enrolled into two dosing cohorts consisting of 20 individuals and doses of 0.25 and 0.4 mg/kg PQ in combination with a full three-day course of DHAP. Participants will first be assigned to the lowest open cohort; enrolment in the next cohort is initiated after tolerability and short-term safety is demonstrated at the preceding lower dose. Furthermore, the investigators will include 3 control groups into the first cohort: i) 10 male participants aged ≥10years with normal haemoglobin levels (≥11g/dL) and a reduced G6PD enzyme function will receive DHAP only, ii) 10 male participants with normal haemoglobin levels (≥11g/dL) and normal G6PD enzyme function will receive 0.25 mg/kg PQ in combination with a full three-day course of DHAP, and iii) 10 male participants with normal haemoglobin levels (≥11g/dL) and normal G6PD enzyme function will receive 0.4 mg/kg PQ with DHAP.

Enrolment and group assignment Individuals who agree to participate for screening and meet all inclusion criteria, will be invited for enrolment. During this, participants and/or their carers will be informed again about the objectives and practical consequences of participation in the current study and asked to sign an informed consent form. The possibility of withdrawal from the study, at any time and without any declaration of the reason will again be pointed out.

After enrolment, participants will be assigned to the lowest-dose open cohort, with enrolment in the second cohort initiated after t
Sponsor: London School of Hygiene and Tropical Medicine

Current Primary Outcome: Haemoglobin concentration relative to baseline value as measured by HemoCue [ Time Frame: 28 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Haematology abnormalities during follow-up: haptoglobin concentration measured in venous blood samples by full blood count analysis [ Time Frame: 28 days ]
  • Biochemistry abnormalities during follow-up: bilirubin concentration [ Time Frame: 28 days ]
  • Biochemistry abnormalities during follow-up: lactate dehydrogenase [ Time Frame: 28 days ]
  • Biochemistry abnormalities during follow-up: creatinine [ Time Frame: 28 days ]
  • Biochemistry abnormalities during follow-up: potassium [ Time Frame: 28 days ]
  • Number of participants with treatment-related adverse events graded and evaluated in terms of relatedness [ Time Frame: 28 days ]
    grading and assessing relatedness will be done following according to criteria of the NIH/NIAID division of microbiology and infectious diseases (DMID)https://www.niaid.nih.gov/LabsAndResources/resources/DMIDClinRsrch/Documents/dmidadulttox.pdf
  • Haematology abnormalities during follow-up: mean corpuscular volume (MCV) measured in venous blood samples by full blood count analysis [ Time Frame: 28 days ]
  • Haematology abnormalities during follow-up: red cell distribution width (RDW) measured in venous blood samples by full blood count analysis [ Time Frame: 28 days ]
  • Haematology abnormalities during follow-up: leukocyte count measured in venous blood samples by full blood count analysis [ Time Frame: 28 days ]


Original Secondary Outcome: Same as current

Information By: London School of Hygiene and Tropical Medicine

Dates:
Date Received: January 5, 2016
Date Started: December 2015
Date Completion: December 2016
Last Updated: September 8, 2016
Last Verified: January 2016