Clinical trial NCT03803644: Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Food Effect of Single Ascending Doses of CC-92480 in Healthy Subjects
Official title: A Phase 1, Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Dosing of CC-92480 and to Explore the Effect of Food on the Bioavailability of CC-92480 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Healthy Subjects
CC-92480
Food Effect
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2019-01-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a two-part study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of CC-92480 and explore the effect of food on the bioavailability of CC-92480 in healthy subjects.

Part 1:

Part 1 is a single-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and pharmacodynamics (PD) of CC-92480 following administration of single oral doses in healthy adult subjects. Part 1 will consist of escalating single doses in sequential groups. Approximately 40 subjects will be enrolled into 5 planned dose level cohorts. Each dose level cohort will consist of 8 subjects; 6 subjects will receive CC-92480 and 2 subjects will receive placebo according to the randomization schedule.

Part 2 Part 2 is a single-center, open-label, randomized, 2-period, 2-way crossover study to explore the effect of food (Food and Drug Administration \[FDA\] standard high-fat breakfast) on the single-dose PK of CC-92480 in healthy adult subjects.


Eligibility criteria: Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Must understand and voluntarily sign a written informed consent form (ICF) prior to any study-related assessments/procedures being performed.
2. Must be able to communicate with the Investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions and examination schedules.
3. Be a healthy male or female of non-childbearing potential of any race, between 18 to 55 years of age (inclusive) at the time of signing the ICF, and in good health as determined by the screening history and PE.
4. Agrees to abide by the requirements and restrictions outlined in the CC-92480 Pregnancy Prevention Plan for Subjects in Clinical Trials.
5. For males: Agree to use barrier contraception not made of natural (animal) membrane (eg, latex or polyurethane condoms are acceptable) when engaging in sexual activity with a female of childbearing potential (FCBP) 1 while on study medication, and for at least 3 months after the last dose of study medication. For females: Female subjects must have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation required) at least 6 months before screening, or be postmenopausal (defined as 24 months without menses before screening, with a plasma follicle-stimulation hormone \[FSH\] level of \> 40 IU/L at screening).
6. Must have a body mass index between 18 and 33 kg/m2 (inclusive) at the time of signing the ICF.
7. No clinically significant laboratory test results as determined by the investigator.
8. At the screening visit, must be afebrile, with supine systolic BP: 90 to 140 mmHg, supine diastolic BP: 50 to 90 mmHg, and pulse rate: 40 to 90 bpm. Eligibility criteria for vital signs performed during check-in and/or predose on Day 1 will be at the discretion of the Investigator. Repeat vital signs may be measured at Investigator discretion.
9. Must have a normal or clinically-acceptable 12-lead ECG at screening. Male subjects must have a corrected QT interval using Fridericia's formula (QTcF) value ≤ 430 msec. Female subjects must have a QTcF value ≤ 450 msec.
10. Subject must agree and be willing to consume a standard high-fat meal (which may contain gluten), for Part 2 subjects only.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. History of any clinically significant and relevant neurological, GI, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders as determined by the Investigator.
2. Any condition that places the subject at unacceptable risk if he or she were to participate in the study, or confounds the ability to interpret data from the study.
3. Use of any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days of the first dose administration.
4. Use of any nonprescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration.
5. Use of CYP3A inducers and inhibitors (including St. John's Wort) within 30 days of the first dose administration.
6. Has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion (ADME), eg, bariatric procedure. Appendectomy and cholecystectomy are acceptable. Prior procedures of unclear ADME significance should be reviewed with the Sponsor's Medical Monitor.
7. Donated blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.
8. History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM\]) within 2 years before dosing, or positive drug screening test reflecting consumption of illicit drugs.
9. History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or positive alcohol screen.
10. Known to have serum hepatitis; known to be a carrier of the hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or hepatitis C antibody (HCV Ab); have a positive result to the test for hepatitis B or hepatitis C virus at screening or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening. Subjects whose results are compatible with prior immunization against hepatitis B may be included at the discretion of the Investigator.
11. Exposure 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).
12. Use of tobacco- or nicotine-containing products within 3 months prior to Day -1 (Period 1 for Part 2).
13. Vaccination within 30 days of dosing or plans to receive vaccination within 30 days after dosing.
14. Systemic infection within 30 days of dosing.

Primary outcomes:
measure: Pharmacokinetics- Cmax Part 1
timeFrame: Day 1
measure: Pharmacokinetics- Tmax Part 1
timeFrame: Day 1
measure: Pharmacokinetics- AUC0-∞ Part 1
timeFrame: Up to 72 hours after dose administration
measure: Pharmacokinetics- AUC0-t Part 1
timeFrame: Up to 72 hours after dose administration
measure: Pharmacokinetics- AUC0-24 Part 1
timeFrame: Up to 24 hours after dose administration
measure: Pharmacokinetics- AUC-t½ Part 1
timeFrame: Up to 72 hours after dose administration
measure: Pharmacokinetics- CL/F Part 1
timeFrame: Up to 72 hours after dose administration
measure: Pharmacokinetics- Vz/F Part 1
timeFrame: Up to 72 hours after dose administration
measure: Pharmacokinetics- Cmax Part 2
timeFrame: Day 1
measure: Pharmacokinetics- Tmax Part 2
timeFrame: Day 1
measure: Pharmacokinetics- AUC0-∞ Part 2
timeFrame: Up to 72 hours after dose administration
measure: Pharmacokinetics- AUC0-t Part 2
timeFrame: Up to 72 hours after dose administration
measure: Pharmacokinetics- AUC0-24 Part 2
timeFrame: Up to 24 hours after dose administration
measure: Pharmacokinetics- AUC-t½ Part 2
timeFrame: Up to 72 hours after dose administration
Secondary outcomes:
measure: Adverse Event(s)
timeFrame: From enrollment until at least 28 days after completion of study treatment
measure: Effect of CC-92480 on ECG parameters- Part 1
timeFrame: Up to day 2
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance-Daytona Beach
state: Florida
Study officials:
affiliation: Celgene
name: Leon Carayannopoulos, MD
role: STUDY_DIRECTOR
References: