Arthemeter-lumefantrine (ART-LUM) is an antimalaria drug manufactured as fixed combination tablets, each containing 20 mg of artemether and 120 mg of lumefantrine. ART-LUM was administrated according to body weight as six consecutive doses: The first dose at diagnosis and the second dose eight hours later, 0- 24-48 hours

Artesunate mefloquine (ASMQ) is an antimalaria drug administered as a combination of artesunate, 4 mg/kg/day, with mefloquine, 8 mg/kg/day orally once a day for 3 days or three times, at an interval of 24 hours (0 h - 24 h - 48 h).

Dihydroartemisinin piperaquine (DHA-PQ ) is an antimalaria drug administered as a combination of dihydroartemisinin, 2.5 mg per kg, with piperaquine phosphate, 20mg per kg daily for 3 days or three times, at an interval of 24 hours

Oral paracetamol is administered at of 50mg/kg body weight per day in three divided doses for fever exceeding 37.5oC.

amoxicillin is an antibiotic administered at 50mg per kg body weight per day for seven days in the event of concomitant bacterial infection, absent on day 0 but present during the follow up.

Quinine is an antimalarial recommended by the WHO and NMCP to be used as second line treatment for malaria. In this study, for cases of treatment failure with the artemisinin based combination therapies, quinine sulphate is administered as a second line or rescue drug at a dose of 25mg base per kg body weight per day in three divided doses for five days. The participant is then classified as ETF or LTF and excluded from the study.

Drug Resistant Malaria Due to Plasmodium Falciparum

Randomization codes were computer-generated by an offsite investigator and provided to a study nurse responsible for treatment allocation. All other study personnel were blinded to the treatment assignments, and patients were not informed of their treatment regimen. Participants from Group 1: AL, Group 2 : DHAP, Group3 : ASMQ were also given appointment card for days 1, 2, 3, 7, 14, 21, 28, 35 and 42 for clinical examination and blood smears. Blood was taken on filter paper on each of these visits.

Arthemeter-lumefantrine

Artequin® is an antimalarial drug presented as infant co-formulation of two separate drugs

Artesunate mefloquine

Malacur®. is an antimalarial drug presentad as co-formulation of two separate drugs

Dihydroartemisinin piperaquine

Paracetamol, is an antipyretic drug, presented as tablets or syrup in infants formulation

Paracetamol

Amoxicillin is an antibiotic with no reported activity on plasmodium

Amoxicillin

quinine sulphate is an antimalaria drug administered as a second line or rescue drug

Quinine

CDC Hospital

Antimalaria Drugs Susceptibility Testing for an Effective Management of Infected Patients in Sub-Sahara Africa

Assessment of Antimalaria Drugs Susceptibility Testing for an Effective Management of Infected Patients in Sub-Sahara Africa

The primary endpoint was the 28-day and 42-day cure rates and was defined as proportion of patients with adequate clinical and parasitological response (ACPR) after 28 and 42 days of follow-up. Absence of parasitemia until day 28 and day 42 irrespective of axillary temperature was categorized as an adequate clinical and parasitologic response (ACPR). Secondary endpoints were early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF), adverse events (clinical and laboratory abnormalities), anaemia (Hematocrit < 30%), clearance rate of fever and parasitaemia, and gametocyte

The ability of the drug to restore hemoglobin level back to normal

The ability of the drug to completely eliminate plasmodium in the blood stream including participant without symptoms of fever

blood sample from patients with parasitaemia at any day of follow-up are analysed by PCR to evaluated the genetic profile of the MSP1 and MSP2

University of Bamenda

Ministry of Science and Technology of the People´s Republic of China

National Institute for Parasitic Disease, Chinese Center for Disease Control and Prevention

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 50mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 100mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 300mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 600mg Tafenoquine will be administered on either Day 1 or Day2 depending on when eligibility is confirmed.

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 15mg Primaquine once daily Days 2-15.

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered.

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered. 15mg Primaquine once daily Days 2-15

On Day 1 and Day 2 600mg Chloroquine will be administered, on Day 3 300mg Chloroquine will be administered

Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.

CQ Only

Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.

TQ + CQ

Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.

PQ + CQ

Total

Sex: Female, Male

Race/Ethnicity, Customized

A participant was considered to have demonstrated recurrence-free efficacy at 6 months if: a) Participant had non-zero P vivax asexual parasite count at Baseline. b) Participant showed initial clearance of P vivax parasitemia defined as two negative asexual P vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval. c) Participant had no positive asexual P vivax parasite count at any assessment prior to or on Study Day 201 following initial parasite clearance. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment. e) Participant is parasite-free at 6 months. Participants were censored if they did not have P.vivax at Baseline, or took a drug with anti-malarial action despite not having malaria parasites, or did not have a 6 month assessment. The number of participants with recurrence-free efficacy at 6 months has been summarized.

Number of Participants With Recurrence-free Efficacy at 6 Months Post Dose

A participant (par) was considered to have demonstrated recurrence-free efficacy at 4 months if: a) Par had non-zero P vivax asexual parasite count at Baseline. b) Par showed initial clearance of P vivax parasitemia. c) Par had no positive asexual P vivax parasite count at any assessment prior to or on Study Day 130 following initial parasite clearance. d) Par did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment after Study Day 109 (up to and including Study Day 130). e) Par is parasite-free at 4 months defined as a negative asexual P vivax parasite count at the first parasite assessment performed after Study Day 109 (up to and including Study Day 130). Par were censored if they did not have P.vivax at Baseline, or took a drug with anti-malarial action despite not having malaria parasites or did not have a 4 month assessment. The number of par with recurrence-free efficacy at 4 months has been summarized.

Number of Participants With Recurrence-free Efficacy at 4 Months Post Dose

Recurrence was defined as the first confirmed presence of P vivax asexual stage parasites after clearance of initial parasitemia following CQ treatment. Time to recurrence was defined as the time (in days) from initial parasite clearance to recurrence. The time to recurrence was analyzed by the Kaplan-Meier method. NA indicates data was not available due to insufficient number of participants with events during the follow up period in the study. The median number of days to recurrence along with 95% confidence interval has been presented for each treatment group.

Time to Recurrence of P Vivax Malaria

Parasite clearance time was defined as time needed to clear asexual parasite from the blood that is, parasite numbers falling below the limit of detection in the thick blood smear and remaining undetectable after 6 to 12 hours. The time taken to achieve parasite clearance was analyzed using Kaplan Meier Methodology. The median parasite clearance time along with 95% confidence interval has been presented for each treatment group.

Time to Parasite Clearance

Fever clearance time was defined as time from first dose of treatment to the time when body temperature falls to normal within Study Days 1-4 and remains normal for at least 48 hours up to the Day 8 visit. Fever clearance was considered to have been achieved once an initial temperature of more than 37.40 degree Celsius is reduced to a value less than or equal to 37.40 degree Celsius and in the absence of value more than 37.40 degree Celsius in the following 48 hours up to the Day 8 visit. The time taken to achieve fever clearance was analyzed using Kaplan Meier Methodology. The median fever clearance time along with 95% confidence interval has been presented for each treatment group.

Time to Fever Clearance

Glucose-6-phosphate dehydrogenase deficiency (G6PD) deficiency is known to be a risk factor for hemolysis in participants treated with 8-aminoquinolines. Blood samples were collected for the evaluation of hemoglobin levels. Hemoglobin decreases of >=30% or >3 grams/deciliter (g/dL) from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL in the first 15 days of the study were considered as protocol defined serious adverse events (SAEs). Number of participants with maximum hemoglobin decline from Baseline over first 29 days of study has been summarized. Safety Population consisted of all randomized participants who received at least one dose of study medication.

Number of Participants With Hemoglobin Decline From Baseline Over First 29 Days

TEAEs are defined as adverse events (AEs) with an onset date and time on or after that of the start of first dose of study medication (including CQ). The number of participants with TEAEs potentially related to hemoglobin decrease has been presented.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Potentially Related to Hemoglobin Decrease

The number of participants who received blood transfusion as a result of hemoglobin decline has been summarized.

Number of Participants Who Received Blood Transfusion

There were no participants with acute renal failure in the study.

Number of Participants With Acute Renal Failure

Methemoglobin assessment was made with the aid of a non-invasive signal extraction pulse CO-Oximeter handheld machine (Masimo). The change from Baseline in percent methemoglobin by treatment, time and sex has been summarized. The last assessment performed prior to the first dose of study medication (CQ or randomized treatment) was considered as Baseline. Change from Baseline was calculated as the post baseline assessment minus the Baseline assessment for percent methemoglobin. Only those participants with data available at the specified data points were analyzed.

Change From Baseline in Percent Methemoglobin

Gastrointestinal tolerability was analyzed by the number of par experiencing gastrointestinal disorders such as abdominal pain, heartburn, diarrhea, constipation, nausea, and vomiting. The number of participants with gastrointestinal disorders for each treatment group has been summarized.

Number of Participants With Gastrointestinal Disorders

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. The number of participants displaying keratopathy in each eye was summarized for each visit. The number of participants with new keratopathy at any time post Baseline was also reported. Ophthalmic Safety Population comprised of all participants in the Safety Population who have results from any eye assessments. Only those participants with data available at the specified data points were analyzed.

Number of Participants With Keratopathy

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Best corrected visual acuity was assessed individually for each eye. Scores were recorded as a ratio. The values were used to derive a logMAR score for statistical analysis where logMAR=-1x log10 (ratio score). The mean and standard deviation of logMAR score for each treatment group has been summarized. High scores were associated with worse vision, and low scores with better vision. Only those participants with data available at the specified data points were analyzed.

Incidence of Visual Field Abnormalities Based on Best Corrected Visual Acuity Test Scores

Ophthalmic assessments were carried out at pre-qualified sites (Manaus) prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Change from Baseline was calculated as the post Baseline assessment minus the Baseline assessment. The number of participants with definite retinal change and questionable (ques) retinal change from Baseline was presented. Only those participants with data available at the specified data points were analyzed.

Number of Participants With Retinal Changes From Baseline

An AE is defined as any untoward medical occurrence in a participant under clinical investigation, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations and is associated with possible drug induced liver injury with hyperbilirubinemia. TEAEs is defined as AEs with an onset date and time on or after that of the start of first dose of study medication (including CQ). Number of participants with TEAEs and serious TEAEs have been presented.

Number of Participants With TEAEs and Serious TEAEs

An AE is defined as any untoward medical occurrence in a participant under clinical investigation, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is defined as AEs with an onset date and time on or after that of the start of first dose of study medication (including CQ). Number of participants with AEs based on severity has been presented.

Number of Participants With TEAEs by Maximum Intensity

Blood samples were collected for the evaluation of hematology parameters including eosinophils, leukocytes, lymphocytes, neutrophils, platelets, reticulocytes and methemoglobin. The number of participants with hematology laboratory data outside the extended normal range (F3) was presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Only those participants with data available at the specified data points were analyzed.

Number of Participants With Hematology Laboratory Data Outside the Reference Range

Blood samples were collected for the evaluation of clinical chemistry parameters including Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk. Phos), Aspartate Aminotransferase (AST), bilirubin, creatine kinase, creatinine, glomerular filtration rate (GFR), indirect bilirubin and urea. The number of participants with clinical chemistry laboratory data outside the extended normal range (F3) was presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Only those participants with data available at the specified data points were analyzed.

Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range

Health outcomes were evaluated based on the total costs spent on treatment, transport, medication and tests. The cost was summarized according to the place at which the participant went to for care (drug shop, trial clinic, other clinic, hospital (inpatient/outpatient), traditional healer, other). The reported costs by type and by site has been summarized. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed.

Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) with a recurrence episode of malaria were included.

First Malaria Recurrence

Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) who had a follow-up visit for recurrence episode of malaria were included.

First Malaria Recurrence Follow-up

Cost Associated With Recurrence Episode of P Vivax Malaria

Health outcomes were evaluated based on the cost of medications purchased. The reported total medication cost for paracetamol associated with recurrence episode of P vivax malaria has been reported by site. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. Medications recorded as "Other" and medications without costs are excluded from the analysis. Only those participants with data available at the specified data points were analyzed.

Cost Incurred With Purchase of Medications Associated With Recurrence Episode of Malaria

Health outcomes were evaluated based on total time lost by participants or care givers due to an episode of malaria. The reported time lost due to recurrence episode of P vivax malaria has been summarized by category and by site. Where categories by site have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed.

Time Lost by Participants or Care Givers From Normal Occupation

Health outcomes were evaluated based on the actions taken by the participants to treat recurrence episode of P vivax malaria. The reported action taken by site is summarized. Where no action by site have been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed.

Number of Participants With Action Taken to Treat Recurrence Episode of P Vivax Malaria

Participants in TQ Only Arms

Oral Clearance (CL/F) of TQ

Apparent population central volume of distribution of TQ

Volume of Distribution (Vc/F) of TQ

Overall Study

GSK Response Center

Malaria, Vivax

600mg Chloroquine given to each subject on Day 1 and Day2 of the trial

Chloroquine 600mg

300mg Chloroquine given to each subject on Day 3 of the trial

Chloroquine 300mg

single dose 50mg Tafenoquine given to subject on treatment arm 1 on Days 1 or 2

Tafenoquine 50mg

single dose 100mg Tafenoquine given to subject on treatment arm 2 on Days 1 or 2

Tafenoquine 100mg

single dose 300mg Tafenoquine given to subject on treatment arm 3 on Days 1 or 2

Tafenoquine 300mg

single dose 600mg Tafenoquine given to subject on treatment arm 4 on Days 1 or 2

Tafenoquine 600mg

15mg Primaquine given once daily to subject on treatment arm 5 on Days 2 to 15.

Primaquine 15mg

600mg Chloroquine given to each subject on Day 1 and Day2 of the trial.

Chloroquine 600mg (Part 2 )

300mg Chloroquine given to each subject on Day 3 of the trial.

Chloroquine 300mg (Part 2 )

single dose 300mg Tafenoquine given to subject on treatment arm 3 on Days 1 or 2.

Tafenoquine 300mg (Part 2)

15mg Primaquine given once daily to subject on treatment arm 3 on Days 2 to 15.

Primaquine 15mg (Part2 )

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

GSK Investigational Site

Ph 2B/3 Tafenoquine (TFQ) Study in Prevention of Vivax Relapse

A Multi-centre, Double-blind, Randomised, Parallel-group, Active Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Tafenoquine (SB-252263, WR238605) in Subjects With Plasmodium Vivax Malaria.

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

parasitemia/nausea

Antimalaria Drugs Susceptibility Testing for an Effective Management of Infected Patients in Sub-Sahara Africa

Ph 2B/3 Tafenoquine (TFQ) Study in Prevention of Vivax Relapse

Il database di erbe medicinali più completo supportato dalla scienza