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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01218932
Other study ID # FTM1001
Secondary ID
Status Completed
Phase Phase 1
First received October 8, 2010
Last updated June 13, 2012
Start date October 2010
Est. completion date March 2012

Study information

Verified date June 2012
Source University of Oxford
Contact n/a
Is FDA regulated No
Health authority Thailand: Ethical Committee
Study type Interventional

Clinical Trial 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 about 12-24 hours depends on each regimen. Subjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period.

Subjects in B group who receive regimen 1 of primaquine (PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission(visit 4) with 8 week wash out period in between.


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 available hypnozoitocidal drug for P.vivax and gametocytocidal agent for Plasmodium falciparum malaria. Despite this enormous use knowledge about the mechanism of activity, pharmacokinetic properties, resistance and toxicity of primaquine are limited. Primaquine at the previously used dose for radical cure (15 mg base/day for 14 days) is also weakly effective against asexual stages of P. vivax malaria [4] The higher dose of 30 mg daily evaluated for malaria prophylaxis is now also generally recommended for radical cure. In the standard radical cure regimen, primaquine is usually given after the 3-day course of chloroquine, but there has been no study to inform timing of dosing so this decision is arbitrary. Despite the multistage specificity against the malaria parasite, and extensive recommendations, primaquine is currently underused because of uncertainties over safety, efficacy and dosage. Primaquine is an oxidant drug and causes haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD). Although several studies of the metabolites of the primaquine and chloroquine have been conducted over the past few years remarkably little is known about the interaction between these two commonly coadministered drugs.

This study is open-label pharmacokinetic study. Healthy 16 volunteers will be recruited to the established volunteer facility at single site at the Hospital for Tropical Diseases to determine the pharmacokinetic properties of primaquine and it's main active metabolites and evaluate any interaction with chloroquine.in order to provide clinical guidance for the optimum primaquine/chloroquine treatment regimens.


Recruitment information / eligibility

Status Completed
Enrollment 16
Est. completion date March 2012
Est. primary completion date October 2011
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 60 Years
Eligibility Inclusion Criteria:

1. Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.

2. Males and Females aged between 18 years to 60 years.

3. 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

4. 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.

5. Read, comprehend, and write at a sufficient level to complete study-related materials.

6. Provide a signed and dated written informed consent prior to study participation.

7. Normal electrocardiogram (ECG) with QTc <450 msec.

8. Willingness and ability to comply with the study protocol for the duration of the trial.

Exclusion Criteria:

1. Females who are pregnant, trying to get pregnant, or are lactating.

2. The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions.

3. A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.

4. 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).

5. Subjects with a family history of sudden cardiac death.

6. 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].

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. Subjects with unstable medical conditions that, in the opinion of the investigator would compromise their participation in the trial

14. Those who, in the opinion of the investigator, have a risk of non-compliance with study procedures.

15. Lack of suitability for participation in this study, for any reason, in the opinion of the investigator.

16. AST or ALT >1.5 upper limit of normal (ULN)

17. Subjects with history of renal disease, hepatic disease, and/or cholecystectomy

18. G6PD deficient.

19. Abnormal methaemoglobin level.

20. Subjects who have anemia, Hb <12 for both male and female

21. History of malaria treatment with Primaquine and/or Chloroquine within 12 months

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
A
Subjects in A group who receive regimen 1 of primaquine (PQ) on the first admission (visit 2) will receive regimen 2 of primaquine and chloroquine combination (PQ and CQ) on second admission (visit 3) after 1 week wash out period and will finish with regimen 3 of Chloroquine (CQ) on the third admission (visit 4) after 8 weeks wash out period.
B
Subjects in B group who receive regimen 1 of primaquine ( PQ) will receive regimen 2 of chloroquine (CQ) on second admission (visit 3) after 1 week wash out period and regimen 3 of primaquine and chloroquine combination (PQ and CQ)on third admission( visit 4) with 8 week wash out period in between.

Locations

Country Name City State
Thailand Hospital For Tropical Diseases Bangkok

Sponsors (2)

Lead Sponsor Collaborator
University of Oxford Mahidol University

Country where clinical trial is conducted

Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary AUC Area under the plasma concentration time AUC 0-8curve for primaquine and metabolites (mPQ) when given alone and together with chloroquine 36 days No
Secondary Cmax Primaquine and metabolites maximum concentrations, chloroquine and metabolites maximum concentration and AUC 36 days No
Secondary Elimination rate Primaquine and metabolites (mPQ) elimination rate constants (mPQ-?z), and elimination half life (mPQ-t1/2),chloroquine metabolite(s) elimination rate constant (mCQ-?z), and elimination half life (mCQ-t1/2) 36 days No
Secondary Adverse events Safety and tolerability parameters, including adverse events, clinical laboratory, and vital signs assessments 36 days Yes
Secondary Pharmacogenetics Pharmacogenetic polymorphisms in the case of unusually high or low drug levels 36 days No
See also
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Completed NCT01074905 - Study on the Treatment of Vivax Malaria Phase 3
Completed NCT04222088 - TES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014
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Completed NCT00682578 - A Comparative Study of Artekin With Standard Malarial Treatment Regimes in Afghanistan Phase 3
Completed NCT00157833 - A Randomized Trial of Coartemether and Artekin for the Treatment of Uncomplicated Malaria in Papua, Indonesia. N/A
Active, not recruiting NCT03529396 - Safety and Efficacy of Different Regimens of Primaquine on Vivax Malaria Treatment in G6PD Deficient Patients Phase 2
Recruiting NCT05874271 - Short Course Primaquine for the Radical Cure of P. Vivax - Papua New Guinea N/A
Completed NCT05958797 - TES of Chloroquine for Pv in the Philippines in 2016
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Completed NCT01640574 - Comparison Between 7 and 14 Day Primaquine Combined With Dihydroartemisinin-piperaquine or 3 Day Chloroquine Radical Cure of P. Vivax (BPD) Phase 3
Completed NCT01076868 - Incidence of Vivax Along the Thai Burma Border N/A
Completed NCT00158561 - Chlorproguanil/Dapsone Compared With Chloroquine and SP for Vivax Malaria Phase 3
Completed NCT01780753 - Primaquine Pharmacokinetics in Lactating Women and Their Infants Phase 1
Completed NCT06044805 - Therapeutic Efficacy of Chloroquine Plus Primaquine in the Treatment of Uncomplicated Plasmodium Vivax Phase 4