Comparison of the ECG Effects Related to Pharmacokinetic Profile of Chloroquine and Piperaquine

• Register: ClinicalTrials.gov
• Last refreshed on: 17 November 2015
• Main ID: NCT02192944
• Date of registration: 01/07/2014
• Prospective Registration: Yes
• Primary sponsor: University of Oxford
• Public title: Comparison of the ECG Effects Related to Pharmacokinetic Profile of Chloroquine and Piperaquine
• Scientific title: Comparison of the Electrocardiographic Effects in Relation to Pharmacokinetic Profile of Chloroquine and Piperaquine in Healthy Thai Subjects
• Date of first enrolment: July 2014
• Target sample size: 16
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02192944
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Health Services Research
• Phase: Phase 4

Countries of recruitment

Thailand

Contacts

• Name: Borimas Hanboonkunupakarn, MD
• Affiliation: Faculty of Tropical Medicine, Mahidol University, Thailand

Key inclusion & exclusion criteria

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. Male and female subjects 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 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) until study completion.

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, until study
completion.

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

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

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 hypertension, 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.

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.

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

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

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

16. Abnormal methaemoglobin level.

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

18. History of antimalarial drugs use within 12 months.



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Healthy

Intervention(s)

Drug: Chloroquine

Drug: Dihydroartemisinin-piperaquine

Primary Outcome(s)

Changes of QTc within 24 hours after dosing [Time Frame: 24 hours after dosing]

Area under the curve [Time Frame: 24 hours after dosing]

Secondary Outcome(s)

Number of participant with adverse event [Time Frame: 24 hours after dosing]

Secondary ID(s)

FTM1401

Source(s) of Monetary Support

Please refer to primary and secondary sponsors