Bioavailability Study of Oral OZ439 Prototype Formulations Administered With Piperaquine Phosphate (PQP)

Malaria Clinical Trial

Official title:

Open Label Study to Investigate the Pharmacokinetics of Prototype Formulations of OZ439 Administered With Piperaquine Phosphate in the Fasted State to Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02083406
• Other study ID #: MMV_OZ439_13_007
• Status: Completed
• Phase: Phase 1
• First received: March 7, 2014
• Last updated: March 17, 2015
• Start date: July 2014
• Est. completion date: July 2014

Study information

• Verified date: March 2015
• Source: Medicines for Malaria Venture
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

A single dose study to investigate how different formulations of OZ439 co-administered with PQP tablest are processed by the body when taken without food

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy males, or healthy females of non-childbearing potential ie surgically sterilised or post-menopausal (amenorrhoea for at least 1 year and confirmed by a follicle stimulating hormone result of =25 IU/mL

2. Age 18 to 55 years of age

3. Body mass index of 18.0 to 30.0 kg/m2 inclusive. Total body weight >50 kg at screening

4. Willing and able to communicate and participate in the whole study

5. Must provide written informed consent

6. Must agree to use an adequate method of contraception

7. Must have liver function tests and haemoglobin within the laboratory reference range at screening and Day -1

8. Must have heart trace measurements within the defined healthy limits at screening, Day -1 and pre-dose

Exclusion Criteria:

1. Male subjects who have currently pregnant partners

2. Evidence or history of clinically significant oncological, pulmonary, chronic respiratory, hepatic, cardiovascular, haematological, metabolic, neurological, immunological, nephrological, endocrine or psychiatric disease, or current infection

3. Clinically relevant abnormalities in the heart trace including any degree of heart block, including asymptomatic bundle branch block

4. Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval

5. History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia

6. Electrolyte disturbances, particularly hypokalemia, hypocalcaemia or hypomagnesaemia.

7. Any condition that could possibly affect drug absorption, such as gastrectomy or diarrhoea

8. History of post-antibiotic colitis

9. History of any drug or alcohol abuse in the past 2 years prior to screening

10. Subjects who have a breath carbon monoxide reading of greater than 10 ppm at screening will be excluded. Subjects who are tobacco users (including smokers and users of snuff, chewing tobacco and other nicotine or nicotine-containing products) must have stopped use within 90 days before screening.

11. Receipt of an investigational drug or participation in another clinical research study within 90 days prior to drug administration.

12. Subjects who are study site employees, or immediate family members of a study site or sponsor employee.

13. Subjects who have previously been enrolled in this study

14. Use of ANY prescription or non-prescription medications, vitamins, herbal supplements or dietary supplements, including protein supplements, within 14 days prior to the first dose of study drug and throughout the study, unless prior approval is granted by both the investigator and the sponsor. An exception will be made for intermittent use of paracetamol and hormone replacement therapy. Paracetamol at doses of, at most, 2 g per day or no more than 3 consecutive days or 6 non consecutive days, are allowed until 24 hours before dosing with study drug. Longer exclusion periods apply for:

1. amiodarone and hydroxychloroquine (210 days)

2. monoclonal antibodies/ immunoglobulins/ other therapeutic proteins and experimental drugs for which the half-life is not known to the investigator (120 days)

3. experimental drugs for which half-life is known to the investigator (5 half lives plus 14 days)

4. chloroquine, piperaquine phosphate and flunarizine (100 days)

5. fluoxetine (75 days)

6. benzodiazepines (for midazolam, lorazepam and triazolam, the exclusion period is 14 days), chlorpromazine, mephenytoin, nortryptyline, phenobarbital, primidone, phenprocoumone and cytochrome P450 3A4 inducers not already mentioned, including but not restricted to, rifampin, carbamazepine, oxcarbazepine, phenytoin and St John's Wort (35 days)

15. Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results

16. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator

17. Positive urine drug screen result at screening or admission to the clinical unit

18. History of intolerance or hypersensitivity to piperaquine or any 4-aminoquinolone, or ascertained or presumptive hypersensitivity to the active principle and/or formulation ingredients; history of anaphylaxis to drugs or allergic reactions in general, that the investigator considers may affect the outcome of the study

19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

20. Presence or history of allergy requiring treatment; hayfever is allowed unless it is active

21. Donation or loss of >400 mL of blood within 90 days prior to drug administration

22. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)

23. Subjects who do not have suitable veins for multiple blood samples as assessed by the investigator at screening

24. Failure to satisfy the investigator of fitness to participate for any other reason

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• 800mg OZ439 prototype formulation 1

• 800mg OZ439 prototype formulation 2

• 800mg OZ439 prototype formulation 3

• 960mg PQP

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Nottingham	Nottinghamshire

Sponsors (2)

Lead Sponsor	Collaborator
Medicines for Malaria Venture	Quotient Clinical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OZ439 AUC(0-168h)	OZ439 Area under the plasma concentration (AUC) versus time curve	Up to 168 hours post-dose	No
Primary	OZ439 Cmax	OZ439 Maximum observed concentration	Up to 168 hours post-dose	No
Secondary	Piperaquine (PQ) AUC(0-168h)	PQ Area under the plasma concentration versus time curve	Up to 168h post-dose	No
Secondary	PQ Cmax	PQ Maximum observed concentration	Up to 168h post-dose	No