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

NCT ID: NCT01732588

Last Updated: 2015-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2012-12-31

Brief 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

Detailed 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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Regimen A - 120mg OZ439 PIB

120mg single dose of OZ439 as powder in bottle (PIB) formulation

Group Type: ACTIVE_COMPARATOR

OZ439 120mg PIB

Intervention Type: DRUG

120mg dose (as free base) of OZ439 as a solution made up from powder in bottle (PIB)

Regimen B - 120 mg OZ439 IR caplet

120 mg single dose of OZ439 immediate release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route

Group Type: EXPERIMENTAL

120 mg OZ439 caplet

Intervention Type: DRUG

120 mg (as free base) of OZ439 immediate-release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route

Regimen C - 120 mg OZ439 caplet via Enterion capsule

120 mg single dose of OZ439 caplet formulation containing nanoparticulate, administered orally via the Enterion capsule and delivered to the proximal small bowel

Group Type: EXPERIMENTAL

120mg OZ439 caplet via Enterion capsule

Intervention Type: DRUG

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)

Interventions

OZ439 120mg PIB

120mg dose (as free base) of OZ439 as a solution made up from powder in bottle (PIB)

Intervention Type: DRUG

120 mg OZ439 caplet

120 mg (as free base) of OZ439 immediate-release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route

Intervention Type: DRUG

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)

Intervention Type: DRUG

Other Intervention Names

Regimen A; Regimen B; Regimen C

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medicines for Malaria Venture

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fiona Macintyre, PhD

Role: STUDY_DIRECTOR

Medicines for Malaria Venture

Locations

Quotient Clinical

Nottingham, Nottingham, United Kingdom

Countries

United Kingdom

Other Identifiers

MMV_OZ439_12_003

Identifier Type: -

Identifier Source: org_study_id