Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Active-control, Double-blind, Double-dummy Study to Evaluate the Efficacy and Safety of Tafenoquine for the Treatment of Plasmodium Vivax in Adults
Brief Summary: This Phase II study is designed to determine whether a single 600 mg dose or 400mg/day for 3 days of tafenoquine is efficacious, and well tolerated for clearing P. vivax malaria infection (blood schizontocidal and gametocytocidal activity) and preventing P. vivax relapse (hypnozoite eradication). It will also further establish the safety and tolerability of these doses of tafenoquine.


Options:
A: Inclusion Criteria:

* ≥ 6 months old
* Microscopic diagnosis of Plasmodium vivax malaria mono-infection
* Participant or parent/guardian is willing and able to give informed consent for participation in the study
* Able (in the Investigators opinion) and willing to comply with all study requirements.

Exclusion Criteria:

* Severe malaria
* History of allergy or adverse reaction to artesunate, piperaquine, chloroquine, or primaquine
* Blood transfusion in the past 3 months
* G6PD deficiency by rapid test
* Hematocrit ≤ 25%
* Pregnancy at the time of screening
* Breastfeeding an infant \< 6 months old
* Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study
B: Inclusion Criteria:

* Participant (or parent/guardian of children below age of consent) is willing and able to give written informed consent to participate in the trial; verbal consent in the presence of a literate witness is required for illiterate patients. In addition, written assent (or verbal assent in the presence of a literate witness for illiterates) from children 12 to 17 years as per local practice.
* Monoinfection with P. vivax of any parasitaemia in countries which use Chloroquine (CQ) as blood schizontocidal therapy. Mixed infections with P. vivax and P. falciparum can be enrolled in countries which use an artemisinin combination therapy.
* Diagnosis based on rapid diagnostic tests.
* Over 6 months of age.
* Weight 5 kg or greater.
* Fever (axillary temperature 37.5 degrees C) or history of fever in the last 48 hours.
* Able, in the investigators opinion, and willing to comply with the study requirements and follow-up.

Exclusion Criteria:

* Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
* Inability to tolerate oral treatment.
* Previous episode of haemolysis or severe haemoglobinuria following primaquine
* Signs/symptoms indicative of severe/complicated malaria or warning signs requiring parenteral treatment- Haemoglobin concentration less than 9 g/dL
* Known hypersensitivity or allergy to the study drugs
* Blood transfusion in last 90 days, since this can mask G6PD deficient status
* A febrile condition due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration)
* Presence of any condition which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal or hepatic disease; severe malnutrition; HIV/AIDS; or severe febrile condition other than malaria); coadministration of other medication known to cause haemolysis or that could interfere with the assessment of antimalarial regimens.
* Currently taking medication known to interfere significantly with the pharmacokinetics of primaquine and the schizontocidal study drugs.
* Prior antimalarial medications in the previous 7 days.
C: Inclusion Criteria:

* Lactating women aged 18 years and older who are breast feeding one infant aged more than 28 days.
* G6PD normal
* History of proven P.vivax malaria that has not been treated with primaquine
* Willingness and ability to comply with the study protocol for the duration of the trial
* Written informed consent provided

Exclusion Criteria:

* Known hypersensitivity to primaquine, defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis
* Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in mother
* Glucose-6-phosphate-dehydrogenase (G6PD) deficiency in infant
* Pregnancy (urine test for HCG to be performed on any woman of child bearing age unless menstruating)
* Blood smear positive for malaria at the time of enrolment
* Presence of intercurrent illness or any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study
* Hematocrit (HCT) \<25% in the mother or \<33% in the infant
* Use of medications other than antipyretics in the past 7 days or Chloroquine in the past 2 months.
* Use of primaquine since most recent malaria episode.
D: Inclusion Criteria:

1. Positive smear for P. vivax.
2. Parasite density \> 500 and \< 200,000/μl
3. Age: 20-60 years old
4. Willing to sign consent form
5. Willing to be hospitalized for 29 days and remain in a malaria free region for 60 days thereafter for follow-up.
6. A female is eligible to enter and participate in this study if she is of:

a non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post-menopausal or, b child-bearing potential, has a negative pregnancy (urine or serum) test at screen, and agrees to comply with recognized contraceptive methods during the treatment stage of the study and for a period of 12 weeks after stopping study drug. Recognized contraceptive methods include, abstinence, implants of levonorgestrel, injectable progestogen, or appropriate double barrier methods using licensed contraceptives such as diaphragm and condom (by the partner) or intrauterine device and condom. The use of oral/patch contraceptives during the study is not considered sufficient contraceptive protection.

Exclusion Criteria:

1. Mixed malaria infections by Field's stain.
2. Female subjects who are pregnant, lactating or unwilling/unable to comply with recognized contraceptive methods during the treatment stage of the study and for a period of 12 weeks after stopping study drug.
3. Symptoms of severe vomiting (no food or inability to take food during the previous 8 hours).
4. Demonstrated glucose-6-phosphate dehydrogenase deficiency.
5. Subject has taken other anti-malarials (mefloquine, primaquine, chloroquine) within the past 30 days by history
6. Clinically significant illness (intercurrent illness e.g. pneumonia, pre-existing condition e.g. renal disease, malignancy or conditions that may affect absorption of study medication e.g. severe diarrhea or any signs of malnutrition as defined clinically).
7. Clinically significant abnormal laboratory values as determined by history, physical examination or routine blood chemistries and hematology values (laboratory guideline values for exclusion are hemoglobin \<7 gm/dL, platelets \< 50,000/μl, White Blood Cell count (WBC) \< 2000/μl, serum creatinine \>2.0mg/dL, or ALT or AST more than 3 times the upper limit of normal for age.
8. History of allergy to chloroquine, mefloquine, tafenoquine, primaquine or any other 8-aminoquinolines.
9. Subject has taken another investigational drug within 30 days or 5 half lives (whichever is longer), of study start.
10. History of previous eye surgery or have evidence of corneal or retinal abnormalities identified in baseline ophthalmological examination.
11. Subjects taking concomitant medications likely to affect renal or ophthalmic function or that are known to be metabolized primarily by the cytochrome P450 isoforms 3A4/5 and 2C9 and whose therapeutic effect occurs within a narrow plasma concentration range (e.g. warfarin, ketoconazole).
12. Subjects whom, after examination by the study ophthalmologist, are judged to be at risk for acute angle closure glaucoma.
13. Females who are pre-menarchal.

Answer: D