A Phase 1, Open-label Study in Healthy Adult Subjects to Evaluate Effects of Cytochrome P450 Inhibition and Induction on the Pharmacokinetics of CC-99677 and the Effects of CC-99677 on the Pharmacokinetics of Digoxin, Metformin, Methotrexate, Midazolam, Rosuvastatin, and Sulfasalazine
Overview
- Phase
- Phase 1
- Intervention
- Rosuvastatin
- Conditions
- Healthy Volunteer
- Sponsor
- Celgene
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Pharmacokinetics-Cmax
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
It is a phase 1, open-label, single-center, three-part study to assess the safety, tolerability, and pharmacokinetics of multiple doses of CC-99677 administered alone or in combination with either methotrexate and sulfasalazine; itraconazole, rifampin, midazolam, or a cocktail of digoxin, metformin, and rosuvastatin in healthy subjects
Detailed Description
This study will allow investigation of potential drug-drug interaction mediated through cytochrome P450 enzymes and drug transporter proteins. During each part, blood samples will be collected at prespecified times for pharmacokinetic assessments. Subject safety will be monitored throughout the study. There will be approximately 16 subjects enrolled into each part.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must satisfy all of the following criteria to be enrolled in the study:
- •Subject is ≥ 18 and ≤ 64 years of age at the time of signing the informed consent form (ICF).
- •Part 1 is open to male subjects ONLY
- •Both male and female subjects may participate in Parts 2-
- •Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- •Subject is in good health, as determined by the Investigator based on a physical examination at screening.
- •Female subjects of childbearing potential (FCBP) are not permitted in Part 1, but are permitted in Parts 2 and 3, and must:
- •Have two (2) negative pregnancy tests as verified by the Investigator prior to the first dose of IP. She must agree to ongoing pregnancy testing during the course of the study, and prior to discharge from the study site. This applies even if the subject practices true abstinence2 from heterosexual contact.
- •Agree to use, and be able to comply with, one highly effective3 non-hormonal method of contraception without interruption, during the study (including any dose interruptions), and for at least 28 days after discontinuation of IP. The female subject's chosen form of highly effective contraception must be effective by the time the female subject is enrolled into the study (eg, contraception should be initiated at least 28 days prior to enrollment) and at least 28 days after discontinuation of IP.
Exclusion Criteria
- •The presence of any of the following will exclude a subject from enrollment:
- •Subject has any significant medical condition (including but not limited to neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- •Subject has any condition that confounds the ability to interpret data from the study.
- •Female subjects are prohibited from participating in Part
- •Female subjects may participate in Parts 2-
- •Subject is pregnant or breastfeeding.
- •Subject was exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
- •Subject has used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days prior to the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer). Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
- •Subject has used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first dose administration. Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
Arms & Interventions
Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin
Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg.
Intervention: Rosuvastatin
Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin
Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg.
Intervention: Metformin
Part 1: CC-99677 with Methotrexate and Sulfasalazine
Fixed-sequence involving CC-99677 + Methotrexate 7.5 mg and sulfasalazine 1000 mg
Intervention: CC-99677
Part 1: CC-99677 with Methotrexate and Sulfasalazine
Fixed-sequence involving CC-99677 + Methotrexate 7.5 mg and sulfasalazine 1000 mg
Intervention: Methotrexate
Part 1: CC-99677 with Methotrexate and Sulfasalazine
Fixed-sequence involving CC-99677 + Methotrexate 7.5 mg and sulfasalazine 1000 mg
Intervention: Sulfasalazine
Part 2: CC-99677 with Itraconazole and Rifampin
Fixed-sequence involving CC-99677 + Rifampin 600 mg and Itraconazole 200 mg
Intervention: CC-99677
Part 2: CC-99677 with Itraconazole and Rifampin
Fixed-sequence involving CC-99677 + Rifampin 600 mg and Itraconazole 200 mg
Intervention: Itraconazole
Part 2: CC-99677 with Itraconazole and Rifampin
Fixed-sequence involving CC-99677 + Rifampin 600 mg and Itraconazole 200 mg
Intervention: Rifampin
Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin
Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg.
Intervention: CC-99677
Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin
Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg.
Intervention: Midazolam
Part 3: CC-99677, Midazolam, Digoxin, Metformin, Rosuvastatin
Fixed-sequence involving CC-99677 + Midazolam 2 mg, Digoxin 0.25 mg, Metformin 500 mg, and Rosuvastatin 10 mg.
Intervention: Digoxin
Outcomes
Primary Outcomes
Pharmacokinetics-Cmax
Time Frame: Up to approximately 72 hours
Maximum observed plasma concentration
Pharmacokinetics-AUC0-t
Time Frame: Up to approximately 72 hours
Area under the plasma concentration-time curve from time zero extrapolated to the last quantifiable concentration
Secondary Outcomes
- Adverse Events (AEs)(From enrollment until at least 28 days after completion of treatment)
- Pharmacokinetics-Cmax(Up to approximately 72 hours)
- Pharmacokinetics-AUC0-t(Up to approximately 72 hours)