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

NCT01732588 | Completed Phase 1 Results

• 1 other identifier: MMV_OZ439_12_003
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Volunteers

Keywords

Bioavailability

Outcome Measures

Primary Outcomes (2)

• OZ439 AUC0-∞

  Area under the plasma concentration-time curve from zero to infinity (AUC0-∞)

  pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose

• OZ439 Cmax

  The maximum observed plasma drug concentrations (Cmax)

  pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose

Secondary Outcomes (1)

• OZ439 Tmax

  pre dose, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post dose

Study Arms (3)

Regimen A - 120mg OZ439 PIB

ACTIVE COMPARATOR

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

Drug: OZ439 120mg PIB

Regimen B - 120 mg OZ439 IR caplet

EXPERIMENTAL

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

Drug: 120 mg OZ439 caplet

Regimen C - 120 mg OZ439 caplet via Enterion capsule

EXPERIMENTAL

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

Drug: 120mg OZ439 caplet via Enterion capsule

Interventions

OZ439 120mg PIB DRUG

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

Also known as: Regimen A

Regimen A - 120mg OZ439 PIB

120 mg OZ439 caplet DRUG

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

Also known as: Regimen B

Regimen B - 120 mg OZ439 IR caplet

120mg OZ439 caplet via Enterion capsule 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)

Also known as: Regimen C

Regimen C - 120 mg OZ439 caplet via Enterion capsule

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males, or females of non-childbearing potential ie surgically sterilised or post-menopausal
• Age 18 to 55 years
• Body mass index of 18 to 30 kg/m2 inclusive
• Total body weight \>50 kg
• Healthy as determined by pre-study medical history, physical examination (including body temperature) and 12-lead ECG
• Must have haematology, clinical chemistry and urinalysis results at screening that are within the reference range or ncs
• Must agree to use an adequate method of contraception
• Must demonstrate their ability to swallow an empty size 000 capsule
• Must be willing and able to communicate and participate in the whole study
• Must provide written informed consent

You may not qualify if:

• Evidence or history of clinically significant oncological, pulmonary, chronic respiratory, hepatic, cardiovascular, haematological, metabolic, neurological, immunological, nephrological, endocrine or psychiatric disease, or current infection
• Clinically relevant abnormalities in the ECG (12 standard leads) and/or QTcF \>450 ms (males) or \>470 ms (females)
• Evidence or history of clinically significant GI disease or surgery (excluding appendectomy or cholecystectomy)
• Any condition that could possibly affect drug absorption, eg gastrectomy or diarrhoea
• History of post-antibiotic colitis
• History of any drug or alcohol abuse in the past 2 years prior to screening
• 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
• Receipt of an investigational drug or participation in another clinical research study within the previous 3 months
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee
• Subjects who have previously been enrolled in this study
• Use of any prescription or non-prescription medications, vitamins, herbal supplements or dietary supplements within 14 days prior to the first dose
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab)or human immunodeficiency virus (HIV-1 or HIV-2 antibody) results
• Positive urine drug screen result
• History of intolerance or hypersensitivity to artemisinins
• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients

Sponsors & Collaborators

• Medicines for Malaria Venture: lead

Study Sites (1)

Quotient Clinical

Nottingham, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

artefenomel; OOS-A regimen; Regimen B

Results Point of Contact

• Title: Dr Fiona Macintyre
• Organization: MMV

macintyref@mmv.org

+41 22 799 4060

Study Officials

• Fiona Macintyre, PhD

  Medicines for Malaria Venture

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: November 26, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 6, 2015
• Results First Posted: February 13, 2015

Record last verified: 2015-02

Locations

GB (1)