Drug-Drug Interaction Study of Pacritinib and CYP450,Transporter Substrates, and CYP450 3A4 in Healthy Male Subjects

• Status: Not yet recruiting
• Trial end date: 2023-08-10
• Target enrollment: 0
• Participant gender: Male

Summary

This is a Phase 1, open-label, fixed-sequence, 2-part DDI study. Subjects will participate in only 1 study part.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: CTI BioPharma
• Collaborator: PPD
• Treatments: Bosentan; Fluconazole

Criteria

Inclusion Criteria:

1. Male 18 to 55 years of age

2. BMI of 18.0 to 32.0 kg/m2

3. Considered by the investigator to be in good general health

4. Has a documented result of genotype testing for CYP2C19 *1/*1 suggesting normal metabolizers.

5. Meets study contraception and sperm donation requirements.

6. Must have adequate venous access for blood draws.

7. Agrees to comply with all protocol requirements.

8. Able to provide written informed consent.

9. Accepts Healthy Volunteers

Exclusion Criteria:

9. History of any clinically significant conditions as specified in the protocol 10. Known clinically relevant history or presence of significant respiratory (eg, interstitial lung disease), GI (eg, GI ulceration, peptic ulceration, GI bleeding, gastroesophageal reflux, or other GI disease affecting gastroesophageal junction), renal, hepatic (eg, known hepatic or biliary abnormalities), hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, metabolic (eg, diabetes) and dermatological or connective tissue disease.

11. Value >1.5 × ULN for any of the following: prothrombin time, partial thromboplastin time, and international normalized ratio.

12. Seated systolic blood pressure >160 mm Hg or ≤90 mm Hg and a diastolic blood pressure of >100 mm Hg or ≤50 mm Hg, inclusive, at screening and check in unless deemed not clinically significant by the investigator, as approved by the sponsor.

13. Seated pulse rate of <50 bpm or >100 bpm and/or an oral body temperature <35.0°C or >37.5°C when vital signs are measured at screening and check in.

14. Clinically significant illness, including viral syndromes, within 3 weeks of dosing.

15. Known clinically significant chronic viral infection 16. History or clinical manifestation of clinically significant cardiovascular, pulmonary, hepatic (eg, hepatitis), renal, hematologic, gastrointestinal (eg, celiac disease, peptic ulcer, gastroesophageal reflux, inflammatory bowel disease), metabolic, allergic, dermatological, neurological, or psychiatric disorder (as determined by the investigator; appendectomy and cholecystectomy [within 3-6 months] are not considered to be clinically significant procedures).

17. History of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or risk factors for torsades de pointes (eg, heart failure, hypokalemia).

18. Evidence or a history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of the first dose of study drug), hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, or neurological disease. Exceptions to this criterion (eg, stable, mild joint disease unassociated with collagen vascular disease) may be made following discussions with the medical monitor.

19. Evidence of neutropenia or any other blood dyscrasia determined to be clinically significant by the investigator.

20. History of a gastrointestinal bleeding. 21. History of a bleeding disorder diagnosed by a doctor (eg, coagulation factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with blood draws.

22. Receipt of blood products within 2 months prior to check-in (Day -1). 23. Donated blood or blood products >450 mL within 30 days before the first dose of study drug.

24. Smoker or has used nicotine or nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 6 months before the first dose of study drug.

25. Positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at screening, check-in, or throughout the study.

26. History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically significant 27. History of relevant drug and/or food allergies (ie, allergy to digoxin, caffeine, midazolam, omeprazole, rosuvastatin, metformin, bosentan, and fluconazole or excipients) or a previous allergic reaction to phenytoin or carbamazepine (applicable for Group B subjects).

28. History of lymphoma, leukemia or other types of malignancy. 29. Current or recent (<30 days before screening) history of clinically significant bacterial, fungal, or mycobacterial infection.

30. Current or recent (<30 days before screening) history of vitamin B12 deficiency.

31. Unable to tolerate oral medication. 32. Major surgery within 4 weeks of study drug administration. 33. Family history of sudden cardiac death not clearly due to acute myocardial infarction.

34. Has any screening or baseline laboratories outside the normal range and deemed clinically significant.

35. The subject has previously received pacritinib. 36. Has used any prescription or over the counter medications, including herbal or nutritional supplements, within 14 days of check-in.

37. Has any condition possibly affecting drug absorption (eg, previous surgery on the gastrointestinal tract, including removal of parts of the stomach, bowel, liver, gallbladder, or pancreas, with the exception of appendectomy).

38. Has used any of the prohibited medications (targeted CYP inducers or inhibitors) from within 15 days (or 5 half-lives, whichever is longer) before the first dose of study drug.

39. Has consumed grapefruit or grapefruit juice, Seville orange or Seville orange-containing products (eg, marmalade), or caffeine- or xanthine-containing products or other CYP3A4 inhibitors, inducers, or transporter substrates within 48 hours before the first dose of study drug and throughout the study.

40. Has consumed pomegranate or pomegranate juice, pomelo fruits or pomelo juice, or alcohol within 72 hours before check-in on Day -1.

41. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening.

42. Involved in strenuous activity or contact sports within 24 hours before the first dose of study drug and throughout the study.

43. Received treatment in another clinical study of an investigational drug (or medical device) or investigational vaccine within 30 days or 5 half-lives (whichever is longer) prior to check-in 44. Not suitable for entry into the study in the opinion of the investigator. 45. Subjects will also refrain from the use of any other prescription medications and/or products within 14 days prior to check-in (Day -1) and during the entire study, unless deemed acceptable by the investigator in consultation with the sponsor. In addition, subjects will refrain from the use of any over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) from 7 days prior to check-in (Day -1) and during the entire study, unless deemed acceptable by the investigator.