Relative Bioavailability and Effect of Food and Esomeprazole on the Pharmacokinetics of PRN1008 in Healthy Volunteers.
Relative Bioavailability and Effect of Food and Esomeprazole on the Pharmacokinetics of PRN1008 in Healthy Volunteers
Clinical Network Services Pty Ltd
12 participants
Aug 22, 2015
Interventional
Conditions
Summary
This will be a single center, four-period, open-label, complete crossover study to investigating the single dose pharmacokinetics of PRN1008 when administered as a liquid formulation compared to a tablet formulation under fasted conditions, the effect of a meal on the single dose pharmacokinetics of PRN1008 when administered as a tablet formulation and also, the effect of prior administration of a Proton Pump Inhibitor on the single dose pharmacokinetics of PRN1008 when administered as a tablet formulation. Participants will be screened for participation within 28 days before dosing. Participants will be admitted to the study unit the day before dosing (Day -1), then dosed in the mornings of Days 1, 3, 5 and 10, and will remain in the clinic up to Day 11, after collection of the final PK sample. Total participation will be approximately 47 days.
Eligibility
Inclusion Criteria7
- Healthy adult male or non-pregnant non-lactating females, 18 to 75 years of age (inclusive) at the time of screening
- Body mass index (BMI) greater than or equal to 18 and less than or equal to 35 (kg/m2) (inclusive) and a minimum body weight of 45 kg.
- Able to participate and comply with all study procedures and restrictions, and willing to provide written informed consent to participate in the study.
- A female subject of childbearing potential with a negative pregnancy test agrees to abstinence or use of condoms plus one other acceptable form of contraception; i.e. intrauterine device, hormonal contraception, or a female diaphragm, until 4 weeks after dosing with study drug OR has only same-sex partners, when this is her preferred and usual lifestyle
- Male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 4 weeks after dosing with the study drug
- Negative urine drug and alcohol testing at screening and check-in (Day -1). Screening urine drug and alcohol testing may be repeated once if deemed appropriate by the site Investigator.
- Willing to or has abstain(ed) from consuming grapefruit or Seville orange containing products from 14 days prior to first dose of study medication through follow-up.
Exclusion Criteria20
- Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV)
- History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
- History of any significant (as determined by the Investigator) drug-related allergic reactions such as, anaphylaxis, Stevens-Johnson syndrome, urticaria or multiple drug allergies.
- Blood donation or significant blood loss within 30 days prior to screening.
- Plasma donation within 14 days prior to the first study drug administration.
- Participation in another clinical trial of a drug or device whereby the last investigational drug/device administration is within 30 days prior to the first study drug administration or 5 half-lives, whichever is longer.
- Surgery within the past three months prior to the first study drug administration determined by the PI to be clinically relevant.
- Personal or family history of prolonged QT syndrome or family history of sudden death.
- QTcF greater than 450 msec (males) or greater than 470 msec (females) or less than 300 msec at screening or baseline visit, unless deemed clinically insignificant by the Investigator.
- Screening ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement as judged by the Investigator.
- Evidence of atrial fibrillation, atrial flutter, complete bundle branch or heart block, Wolff-Parkinson-White Syndrome, or cardiac pacemaker at screening or baseline visit.
- Seated resting systolic blood pressure (SBP) greater than 150 or less than 90 mm Hg, or diastolic blood pressure greater than 95 or less than 50 mm Hg.
- Hypersensitivity or history of idiosyncratic reaction to any components or excipients of the investigational formulation
- Regular alcohol consumption greater than 14 units per week (1 unit equals half a pint beer, 25 mL of 40 percent spirit or a 125 mL glass of wine).
- Active infection
- Participant is febrile, temperature greater 37.5 degrees centigrade (assessed at Screening and at Baseline (Day -1))
- Any acute illness within 30 days prior to Day 1 unless deemed clinically insignificant by the Investigator and discussed with the Sponsor.
- History of seizure, whether epileptic, paroxysmal, or of unknown origin
- Failure to satisfy the Investigator of fitness to participate for any other reason
- History or presence of any other medical condition that makes the participant unsuitable for the study in the opinion of the Investigator.
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Interventions
This will be a single center, four-period, open-label, complete crossover (meaning subjects will receive all treatments) study to investigate: * The single dose pharmacokinetics of PRN1008 when administered as a liquid formulation compared to a tablet formulation under fasted conditions (no food for at least 8 hours prior to dosing, water permissible until 1 hour pre-dose). * The effect of a meal on the single dose pharmacokinetics of PRN1008 when administered as a tablet formulation. * The effect of prior administration of a Proton Pump Inhibitor on the single dose pharmacokinetics of PRN1008 when administered as a tablet formulation. Participants will be screened for participation within 28 days before dosing. Participants will be admitted to the study unit the day before dosing (Day -1), then dosed in the mornings of Days 1, 3, 5 and 10, and will remain in the clinic up to Day 11, after collection of the final PK sample. All participants will complete all four Periods of the study Participants will be randomized to order of treatment (1, 2 & 3) for the first three Periods. All participants will receive Treatment 4 as the final treatment. Therefore, the final Period will be identical for all participants. Treatments are as listed below. Doses will be administered approximately 48 hours apart for the first three treatments: Treatment 1 Immediately prior to and following a single oral 300 mg dose of PRN1008 liquid formulation, blood samples will be obtained over a period of 24 hours for determination of the PRN1008 PK profile. Participants will be in a fasted state (i.e an overnight fast -no food-of at least 8 hours, water permissible until 1 hr pre-dose).Food will be restricted until 4 hours after dosing. Treatment 2 Immediately prior to and following a single oral 300 mg dose of PRN1008 tablet formulation, blood samples will be obtained over a period of 24 hours for determination of the PRN1008 PK profile. Participants will be in a fasted state (i.e an overnight fast -no food-of at least 8 hours, water permissible until 1 hr pre-dose).Food will be restricted until 4 hours after dosing. Treatment 3 Immediately prior to and following a single oral 300 mg dose of PRN1008 tablet formulation, blood samples will be obtained over a period of 24 hours for determination of the PRN1008 PK profile. Participants will be in a fed state (following an overnight fast of at least 8 hours, and water restricted for 1 hour before food administration, participants will receive a standardized moderate fat meal (breakfast). The meal will be started 30 minutes prior to dosing and ingested within 30 minutes.Further food will be restricted until 4 hours after dosing. Treatment 4 Following collection of the final PK sample from Period 3, participants will begin dosing esomeprazole 40 mg once daily (oral capsule) in the morning, on Days 6 – 10. On Day 10, immediately prior to and following a single oral 300 mg dose of PRN1008 tablet formulation, blood samples will be obtained over a period of 24 hours for determination of the PRN1008 PK profile. The Day 10 PRN1008 dose will be administered in a fasted state (i.e an overnight fast -no food-of at least 8 hours, water permissible until 1 hr pre-dose). Food will be restricted until 4 hours after dosing. All doses are administered and monitored by study staff to ensure compliance. There are 6 possible sequences in which the listed treatments will be completed: * 1234 * 1324 * 2134 * 2314 * 3124 * 3214 Following discharge from the study unit, subjects will return for a follow-up assessment one week (plus or minus 2 days) after final study drug administration. The total duration for participants will be up to approximately 47 days.
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ACTRN12615000936527