CompletedPhase 1ACTRN12616001557426

A Phase 1, Single-Center, Open-label Study to Evaluate the Safety and Pharmacokinetics of Two Tablet Formulations of PRN1008

A Phase 1, Single-Center, Open-label Study to Evaluate the Safety and Pharmacokinetics of Two Tablet Formulations of PRN1008 in healthy adult volunteers.

Sponsor

Principia Biopharma Australia Pty Ltd

Enrollment

14 participants

Start Date

Sep 12, 2016

Study Type

Interventional

Conditions

Rheumatoid Arthritis Pemphigus Vulgaris

Summary

This will be a single-center, open-label, 4-period study to investigate the relative bioavailability of a single dose of PRN1008 when administered as a new tablet formulation compared to the current tablet formulation under fasted and fed conditions. Period 1 is intended to investigate the pharmacokinetics of the 100mg new formulation tablet at a 200mg dose, and to determine an appropriate dose for the new tablet formulation to be used in Periods 2 to 4, the relative bioavailability crossover portion of the study. Participants will be screened for this study within 28 days before dosing. Total length of participation in the study for participants is 76 days from screening through study completion.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria7

Healthy adult male or non-pregnant, non-lactating females, 18 to 65 years of age (inclusive) at the time of screening
Body mass index (BMI) greater than or equal to 18 (kg/m2) (inclusive), 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 12 weeks after dosing with the study drug
Negative urine drug/alcohol testing at screening and check-in (Day -1). Screening urine drug/alcohol testing may be repeated once if deemed appropriate by the site Investigator
Willing to abstain from consuming grapefruit- or Seville orange-containing products from 14 days prior to first dose of study medication through follow-up

Exclusion Criteria23

Use of any prescription or over-the-counter (OTC) medication, including herbal products and supplements, within the 14 days or 5 half-lives prior to Day 1 (whichever is longer). Use of less than or equal to 2g paracetamol per day is allowed prior to and during the study.
Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C antibodies (HCV)
Use of more than two tobacco/nicotine-containing products per month within 6 months prior to the first study drug administration
History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
Regular alcohol consumption of greater than 14 units per week (1 unit = 1/2 pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
History of any significant (as determined by the Investigator) drug-related allergic reactions such as, anaphylaxis, Stevens-Johnson syndrome, urticarial 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 prior to dosing, 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 prior to dosing
Semi-supine 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 prior to dosing.
Hypersensitivity or history of idiosyncratic reaction to any components or excipients of the investigational formulation
Active infection
Participant is febrile, temperature greater than 37.5 degrees C assessed at screening or prior to dosing
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 within the past 5 years, 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, open-label, 4-period crossover study (meaning subjects will receive all treatments) to investigate: 1) The single dose pharmacokinetics of PRN1008 when administered as n

This will be a single center, open-label, 4-period crossover study (meaning subjects will receive all treatments) to investigate: 1) The single dose pharmacokinetics of PRN1008 when administered as new tablet formulation compared to the current tablet formulation under fasted conditions (no food for at least 8 hours prior to dosing, water permissible until 1 hour pre-dose). 2) The effect of a moderate fat meal on the single dose pharmacokinetics of PRN1008 when administered as a new 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 in Period 1 (Day -1). Following an overnight fast of at least 8 hours, participants will receive a single oral 200 mg dose of the new tablet (Treatment 1) formulation under fasting conditions and will remain in the clinic until the final PK and PD samples are collected on the morning of Day 2. Participants will be contacted 7 days (+/- 2 days) following dosing in Period 1 to collect safety and adverse event information. Following a washout of up to 28 days to facilitate Period 1 data review of the safety and tolerability, and pharmacokinetic and pharmacodynamic parameters of the new tablet formulation by the Sponsor in consultation with the Principal Investigator, the dose to be used in Periods 2-4 will be confirmed and participants will be re-admitted to the study unit the day before dosing in Period 2 (Day -1). The dose of PRN1008 new tablet formulation selected for Periods 2-4 will not exceed 800 mg and will be chosen to approximate the expected exposure (AUC0-8) of a single 400 mg IR tablet dose. Treatments for Periods 2 to 4 are listed below. Doses will be administered at least 48 hours apart. * Treatment 2 (Test Formulation Fasted): A single oral dose [TBD] not to exceed 800 mg of PRN1008 administered following an overnight fast of at least 8 hours as new tablet formulation (100mg tablet) under fasted conditions * Treatment 3 (Test Formulation Fed): A single oral dose [TBD] not to exceed 800 mg of PRN1008 administered as a new tablet formulation (100 mg tablet) under fed conditions following a moderate fat meal * Treatment4 (Reference Formulation Fasted): A single oral 400 mg dose of PRN1008 administered as the current tablet formulation (300 mg tablet and/ or 100 mg tablet(s)) under fasted conditions following an overnight fast of at least 8 hours All doses are administered and monitored by study staff to ensure compliance. There are 6 possible sequences in which the listed treatments will be administered: - 1, 2, 3, 4 - 1, 2, 4, 3 - 1, 4, 2, 3 - 1, 4, 3, 2 - 1, 3, 4, 2 - 1, 3, 2, 4 Following discharge from the study unit after Period 4, subjects will return for a Follow-Up visit and assessments on Day 7 +/- 2 days after the final study drug administration.