Pharmacokinetic Study of Primaquine and Chloroquine in Healthy Subjects

NCT01218932 | Completed Phase 1

• 1 other identifier: FTM1001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Vivax Malaria

Keywords

primaquine; chloroquine; pharmacokinetic; interactions

Outcome Measures

Primary Outcomes (1)

• AUC

  Area under the plasma concentration time AUC 0-∞curve for primaquine and metabolites (mPQ) when given alone and together with chloroquine

  36 days

Secondary Outcomes (4)

• Cmax

  36 days

• Elimination rate

  36 days

• Adverse events

  36 days

• Pharmacogenetics

  36 days

Study Arms (2)

A

EXPERIMENTAL

Primaquine only, followed by chloroquine/primaquine, followed by chloroquine only

Drug: A

B

ACTIVE COMPARATOR

Primaquine alone, followed by chloroquine, followed by chloroquine/primaquine

Drug: B

Interventions

A DRUG

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.

A

B DRUG

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.

B

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol University: collaborator

Study Sites (1)

Hospital For Tropical Diseases

Bangkok, Thailand

Location

Related Publications (1)

• Pukrittayakamee S, Tarning J, Jittamala P, Charunwatthana P, Lawpoolsri S, Lee SJ, Hanpithakpong W, Hanboonkunupakarn B, Day NP, Ashley EA, White NJ. Pharmacokinetic interactions between primaquine and chloroquine. Antimicrob Agents Chemother. 2014 Jun;58(6):3354-9. doi: 10.1128/AAC.02794-13. Epub 2014 Mar 31.

  PMID: 24687509 DERIVED

MeSH Terms

Conditions

Malaria, Vivax

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Podjanee Jittamala, MD

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 11, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: March 1, 2012
• Last Updated: June 14, 2012

Record last verified: 2012-06

Locations

TH (1)