A Phase I, Single-center, Open-label Fixed-sequence Study to Assess the Effects of PRN1008 on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, in Healthy Adults
- Conditions
- Healthy VolunteersRheumatoid ArthritisInflammatory and Immune System - Autoimmune diseases
- Registration Number
- ACTRN12614001303639
- Lead Sponsor
- Principia Biopharma Australia Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 12
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maximum observed plasma concentration (Cmax) of midazolam and alpha- hydroxymidazolam.[Day 1 and Day 4 : Pre-dose (prior to midazolam dosing) and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours after midazolam dosing.<br>];Area under the plasma concentration-time curve (AUC) of midazolam and alpha- hydroxymidazolam.[Day 1 and Day 4 : Pre-dose (prior to midazolam dosing) and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours after midazolam dosing.<br>]
- Secondary Outcome Measures
Name Time Method