Status:
COMPLETED
Pharmacokinetic Study of Primaquine and Chloroquine in Healthy Subjects
Lead Sponsor:
University of Oxford
Collaborating Sponsors:
Mahidol University
Conditions:
Vivax Malaria
Eligibility:
All Genders
18-60 years
Phase:
PHASE1
Brief Summary
This is a standard pharmacokinetic interaction study. Subjects will be randomized to be either group A or B. Group A. Subjects will have 3 hospitalizations to complete. Each hospitalization will be ab...
Detailed Description
Chloroquine and primaquine, has been first therapy for Plasmodium vivax and ovale malaria for over 50 years, and has been part of National policy in Thailand for decades. Primaquine is the only availa...
Eligibility Criteria
Inclusion
- Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.
- Males and Females aged between 18 years to 60 years.
- A female is eligible to enter and participate in this study if she is: of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels \>40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy or of childbearing potential, has a negative serum pregnancy test at screening and urine pregnancy test prior to start the study drug in each period, and abstain from sexual intercourse or agrees to using effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study until completion of the follow-up procedures
- A male is eligible to enter and participate in this study if he: agrees to abstain from (or use a condom during) sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures.
- Read, comprehend, and write at a sufficient level to complete study-related materials.
- Provide a signed and dated written informed consent prior to study participation.
- Normal electrocardiogram (ECG) with QTc \<450 msec.
- Willingness and ability to comply with the study protocol for the duration of the trial.
Exclusion
- Females who are pregnant, trying to get pregnant, or are lactating.
- The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions.
- A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.
- Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points (heart failure, hypokalemia).
- Subjects with a family history of sudden cardiac death.
- A creatinine clearance \<70 mL/min as determined by Cockcroft-Gault equation:
- CLcr (mL/min) = (140 - age) \* Wt / (72 \* Scr) (multiply answer by 0.85 for females) Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dL \[Cockcroft, 1976\].
- History of alcohol or substance abuse or dependence within 6 months of the study: History of regular alcohol consumption averaging \>7 drinks/wk for women or \>14 drinks/wk for men. One drink is equivalent to 12 g alcohol = 5 oz (150 mL) of wine or 12 oz (360 mL) of beer or 1.5 oz (45 mL) of 80 proof distilled spirits within 6 months of screening.
- Use of prescription or non-prescription drugs except paracetamol at doses of up to 2 grams/day, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise subject safety; the investigator will take advice from the manufacturer representative as necessary.
- The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication.
- The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to the first dose of study medication until collection of the final pharmacokinetic sample during each regimen.
- Subjects who have donated blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period. Note: This does not include plasma donation.
- Subjects who have a history of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the trial. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
- Subjects with unstable medical conditions that, in the opinion of the investigator would compromise their participation in the trial
- Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.
- Lack of suitability for participation in this study, for any reason, in the opinion of the investigator.
- AST or ALT \>1.5 upper limit of normal (ULN)
- Subjects with history of renal disease, hepatic disease, and/or cholecystectomy
- G6PD deficient.
- Abnormal methaemoglobin level.
- Subjects who have anemia, Hb \<12 for both male and female
- History of malaria treatment with Primaquine and/or Chloroquine within 12 months
Key Trial Info
Start Date :
October 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 1 2012
Estimated Enrollment :
16 Patients enrolled
Trial Details
Trial ID
NCT01218932
Start Date
October 1 2010
End Date
March 1 2012
Last Update
June 14 2012
Active Locations (1)
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1
Hospital For Tropical Diseases
Bangkok, Thailand