A Comparison of the Bioavailability of OZ439 When Delivered Directly to the Small Intestine, or Via the Oral Route

Healthy Volunteers Clinical Trial

Official title:

Three Way Randomised CrossOver Study in Healthy Subjects to Compare the Relative Bioavailability of Nanoparticulate OZ439 Delivered Via the Enterion™ Capsule to the Proximal Small Bowel With Orally Administered OZ439 as PIB Suspension and Orally Administered Nanoparticulate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01732588
• Other study ID #: MMV_OZ439_12_003
• Status: Completed
• Phase: Phase 1
• First received: October 22, 2012
• Last updated: February 17, 2015
• Start date: November 2012
• Est. completion date: December 2012

Study information

• Verified date: February 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

The purpose of this study is to determine the bioavailability of nanoparticulate OZ439 delivered to the proximal small bowel (PSB) via the Enterion™ capsule relative to oral OZ439 suspension (current "powder in bottle" [PIB]) and oral nanoparticulate OZ439.

The study will also characterise the plasma concentration time profile of OZ439 when delivered via Enterion capsule to the PSB in comparison with OZ439 PIB formulation delivered orally and nanoparticulate OZ439 delivered orally Safety and tolerability of OZ439 formulations will be determined following delivery to the PSB and administered orally

Description:

Previous clinical studies with OZ439 have shown variable PK and a food effect. One hypothesis is that this may be related to a 'common ion effect' leading to precipitation of the drug as a less soluble hydrochloride salt in the stomach, resulting in variable absorption of the drug. This study is designed to investigate the possibility of improving the PK profile by delivering the drug directly to the PSB, thereby bypassing the stomach. The study will compare a previously dosed PIB formulation with oral delivery of a nanoparticulate as a caplet formulation. The same caplet formulation containing nanoparticulate will be administered to the PSB via the Enterion capsule.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy males, or females of non-childbearing potential ie surgically sterilised or post-menopausal

2. Age 18 to 55 years

3. Body mass index of 18 to 30 kg/m2 inclusive

4. Total body weight >50 kg

5. Healthy as determined by pre-study medical history, physical examination (including body temperature) and 12-lead ECG

6. Must have haematology, clinical chemistry and urinalysis results at screening that are within the reference range or ncs

7. Must agree to use an adequate method of contraception

8. Must demonstrate their ability to swallow an empty size 000 capsule

9. Must be willing and able to communicate and participate in the whole study

10. Must provide written informed consent

Exclusion Criteria:

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

2. Clinically relevant abnormalities in the ECG (12 standard leads) and/or QTcF >450 ms (males) or >470 ms (females)

3. Evidence or history of clinically significant GI disease or surgery (excluding appendectomy or cholecystectomy)

4. Any condition that could possibly affect drug absorption, eg gastrectomy or diarrhoea

5. History of post-antibiotic colitis

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

7. Subjects who have a breath carbon monoxide reading of greater than 10 ppm at screening. 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

8. Receipt of an investigational drug or participation in another clinical research study within the previous 3 months

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

10. Subjects who have previously been enrolled in this study

11. Use of any prescription or non-prescription medications, vitamins, herbal supplements or dietary supplements within 14 days prior to the first dose

12. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab)or human immunodeficiency virus (HIV-1 or HIV-2 antibody) results

13. Positive urine drug screen result

14. History of intolerance or hypersensitivity to artemisinins

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

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

17. Donation or loss of >400 mL of blood within the previous 3 months

18. Haemoglobin result below the lower limit of the reference range

19. Regular alcohol consumption in males >21 units per week and females >14 units per week

20. Subjects who do not have suitable veins

21. Acute diarrhoea or constipation in the 7 days before the predicted first study day.

22. Presence of non-removable metal objects in the abdomen

23. Radiation exposure exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years

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: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• OZ439 120mg PIB
120mg dose (as free base) of OZ439 as a solution made up from powder in bottle (PIB)
• 120 mg OZ439 caplet
120 mg (as free base) of OZ439 immediate-release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route
• 120mg OZ439 caplet via Enterion capsule
120 mg OZ439 (as free base) in an immediate release (IR) caplet formulation containing nanoparticulate,administered orally via the Enterion capsule and delivered directly to the proximal small bowel (PSB)

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Medicines for Malaria Venture

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OZ439 AUC0-8	Area under the plasma concentration-time curve from zero to infinity (AUC0-8)	pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose	No
Primary	OZ439 Cmax	The maximum observed plasma drug concentrations (Cmax)	pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose	No
Secondary	OZ439 Tmax	Time of maximum observed plasma drug concentrations (Tmax)	pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose	No

External Links

•   Company website