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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Medicines for Malaria Venture
ClinicalTrials.gov Identifier:
NCT01732588
First received: October 22, 2012
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Malaria
Drug: OZ439 120mg PIB
Drug: 120 mg OZ439 caplet
Drug: 120mg OZ439 caplet via Enterion capsule
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Medicines for Malaria Venture:

Primary Outcome Measures:
  • The area under the concentration versus time curve (AUC) for OZ439 in each regimen [ Time Frame: pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose ] [ Designated as safety issue: No ]
  • Peak plasma concentration of OZ439 for rech regimen (Cmax) [ Time Frame: pre dose, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • plasma concentration versus time profiles for each regimen [ Time Frame: pre dose, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose ] [ Designated as safety issue: No ]
    Tlag, Tmax, Cmax, landa-Z and t1/2el will be measured

  • safety laboratory tests [ Time Frame: screening (Day -28 to day -2), 48 hours, final follow-up ] [ Designated as safety issue: Yes ]
    clinical chemistry and urinalysis

  • 12 lead ECG [ Time Frame: screening (Day -28 to Day -2), pre-dose, 2, 4, 8, 24, 48 hours post dose and final follow-up ] [ Designated as safety issue: Yes ]
  • adverse events [ Time Frame: screening (Day -28 to day -2), pre dose, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post dose and final follow up ] [ Designated as safety issue: Yes ]
  • vital signs [ Time Frame: screening (Day -28 to day -2), pre dose, 2, 4, 8, 24 hours post dose and final follow up ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: November 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Regimen A 'OZ439 120mg PIB'
120mg OZ439 provided as powder in bottle (PIB) formulation
Drug: OZ439 120mg PIB
120mg dose (as free base) of OZ439 as a solution made up from powder in bottle (PIB)
Active Comparator: Regimen B '120 mg OZ439 caplet'
120 mg OZ439 immediate-release (IR) caplet formulation containing nanoparticulate, administered directly via the oral route
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
Active Comparator: Regimen C '120mg OZ439 caplet via Enterion capsule'
120 mg OZ439 caplet formulation containing nanoparticulate, administered orally via the Enterion capsule and delivered to the proximal small bowel (PSB)
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01732588

Locations
United Kingdom
Quotient Clinical
Nottingham, United Kingdom, NG11 6JS
Sponsors and Collaborators
Medicines for Malaria Venture
Investigators
Study Director: Fiona Macintyre, PhD Medicines for Malaria Venture
  More Information

Additional Information:
No publications provided

Responsible Party: Medicines for Malaria Venture
ClinicalTrials.gov Identifier: NCT01732588     History of Changes
Other Study ID Numbers: MMV_OZ439_12_003
Study First Received: October 22, 2012
Last Updated: January 25, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Medicines for Malaria Venture:
malaria
bioavailability

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on July 22, 2014