Relative Bioavailability and Effect of Food and Esomeprazole on the Pharmacokinetics of PRN1008 in Healthy Volunteers.

Phase 1

Completed

• Conditions: Rheumatoid Arthritis; Inflammatory Bowel Disease; Systemic Lupus Erythematosus; Inflammatory and Immune System - Autoimmune diseases

• Registration Number: ACTRN12615000936527
• Lead Sponsor: Clinical Network Services Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-09-08
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

* 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 Criteria

* 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.
*Resting HR less than 45 bpm or greater than 90 bpm at screening or baseline (Day -1) visit (the heart rate recorded from vital sign assessment will be utilised for this exclusion criteria).
* 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Relative oral bioavailability (AUC, Cmax) of PRN1008 when administered as a tablet (test formulation) compared to a liquid (reference formulation) as determined by plasma assay.<br>[Time 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours after PRN1008 dosing on Days 1, 3, 5 and 10. <br>];Single dose PK of PRN1008, including plasma Cmax, Tmax, AUC and plasma half-life.[Time 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours after PRN1008 dosing on Days 1, 3, 5 and 10. ];Impact of food on the PK of PRN1008 (AUC, Cmax) when administered as a tablet as determined by plasma assay.<br> [Time 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours after PRN1008 dosing on Days 1, 3, 5 and 10. ]