None listed
Conditions
Brief summary
This will be a single center, open-label, fixed-sequence study to investigate the effects of a single dose of PRN1008 on the PK of midazolam, a CYP3A4 substrate, in healthy participants. One cohort of 12 participants will be studied.
Interventions
This will be a single centre, open-label, fixed-sequence study to investigate the effects of PRN1008 on the PK of midazolam, a CYP3A4 substrate, in healthy participants.
Participants will be screened for participation in this study within 28 days before dosing. Participants will be admitted to the study unit the day before dosing (Day -1) and will remain in the clinic up to Day 5, after collection of the final PK sample.
Participants enrolled will complete a two-period, fixed sequence study:
P
This will be a single centre, open-label, fixed-sequence study to investigate the effects of PRN1008 on the PK of midazolam, a CYP3A4 substrate, in healthy participants. Participants will be screened for participation in this study within 28 days before dosing. Participants will be admitted to the study unit the day before dosing (Day -1) and will remain in the clinic up to Day 5, after collection of the final PK sample. Participants enrolled will complete a two-period, fixed sequence study: Period 1: Study Days 1 to 3. Following a single oral 2 mg dose of midazolam on Day 1, blood samples will be obtained over a period of 24 hours to characterize the PK profile of midazolam and alpha-hydroxymidazolam. Period 2: Study Days 4 to 5 On Day 4, participants will receive an oral 600 mg dose of PRN1008 one hour prior to receiving an oral 2 mg dose of midazolam. Blood samples for determination of PRN1008, midazolam and alpha-hydroxymidazolam PK will be obtained over a period of 25 hours. For both periods, subjects will be monitored on dosing days under supervision of the researcher to ensure administration of the products has been completed in accordance to protocol. Following discharge from the study unit, participants will return for a final follow-up assessment between day 11 to 14.
Sponsors
Principia Biopharma Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adult male and/or females, 18 to 55 years of age (inclusive) at the time of screening. 2. Body mass index (BMI) equal to or greater than 18 and equal to or less than 30 kg/m2 (inclusive) and a minimum body weight of 45 kg. 3. Able to participate and comply with all study procedures and restrictions, and willing to provide written informed consent to participate in the study. 4. If male, agrees to be sexually abstinent or to use a condom or other adequate barrier method of contraception when engaging in sexual activity from study check-in through completion of the end-of study. Participants will be advised to use adequate contraception for 30 days following the last administration of the study drug, and to not donate sperm during this same period of time. In the event that the sexual partner is surgically sterile, use of adequate method of contraception is not necessary. 5. Female participants must be surgically sterile or post-menopausal (no spontaneous menstrual period for at least one year), confirmed by FSH greater than 40 mIU/mL. Sterilization procedure must have been completed at least 6 months prior to Day 1. a. Essure sterilization (with a copy of the confirmation test) and be using an adequate barrier method (condom or diaphragm) throughout the study. b. bilateral tubal ligation and be using an adequate barrier method (condom or diaphragm) throughout the study. c. hysterectomy. d. bilateral oophorectomy. 6. Negative drug/alcohol testing at screening and check-in (Day -1). Screening drug/alcohol testing may be repeated once if deemed appropriate by the site investigator. 7. Willing to abstain from consuming grapefruit or Seville orange containing products from 7 days prior to Day 1 through follow-up.
Exclusion criteria
1. Pregnant or lactating women. 2. Women of child-bearing potential. 3. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HCV). 4. Any active acute or chronic disease judged to be clinically significant by the site investigator. 5. Use of more than 1-2 tobacco/nicotine-containing products per month within 6 months prior to Day 1. 6. Participant is febrile, temperature greater than 37.5 degrees Celsius. 7. History or presence of alcoholism or drug abuse within 2 years prior to Day 1. 8. History of any significant (as determined by the Investigator) drug-related allergic reactions such as,anaphylaxis, Stevens-Johnson syndrome, urticaria or multiple drug allergies. 9. Use of any over-the-counter (OTC) medication, including herbal products, within 7 days prior to Day 1. Use of any prescription medication within 14 days prior to Day 1 or 5 half-lives, whichever is longer. 10. Blood donation or significant blood loss within 60 days prior to screening. 11. Plasma donation within 14 days prior to Day 1. 12. Participation in another clinical trial of a drug or device whereby the last investigational drug/device administration is within 60 days prior to Day 1 or 5 half-lives, whichever is longer. 13. Surgery within the past three months prior to Day 1 determined by the site investigator to be clinically relevant. 14. Personal or family history of prolonged QT syndrome or family history of sudden death. 15. QTcF greater than 450 msec (males) or greater than 470 msec (females) or less than 300 msec at screening or baseline visit, or deemed clinically significant by the site investigator. 16. Screening ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement as judged by the site investigator. 17. Evidence of atrial fibrillation, atrial flutter, complete bundle branch block, Wolff-Parkinson-White Syndrome or cardiac pacemaker at screening or baseline visit. 18. Seated resting systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, or diastolic blood pressure greater than 90 or less than 50 mm Hg. 19. Resting HR less than 45 bpm or greater than 90 bpm at screening or baseline visit. 20. Hypersensitivity or history of idiosyncratic reaction to any components or excipients of the investigational formulation. 21. Any contraindication to the use of midazolam including, but not limited to: hypersensitivity to benzodiazepines or formulation ingredients, myasthenia gravis, severe respiratory insufficiency and sleep apnea syndrome. 22. Regular alcohol consumption >14 units per week(1 unit half a pint of beer, 25 mL of 40 percent spirit or a 125 mL glass of wine). 23. Failure to satisfy the site investigator of fitness to participate for any other reason. 24. Active infection. 25. History of seizure, whether epileptic, paroxysmal or of unknown origin. 26. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological or psychiatric disease. 27. Any acute illness within 30 days prior to Day 1.
Outcome results
None listed