A Phase 1, Two-Part Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of CC-92480; the Relative Bioavailability Among Two Formulations of CC 92480; and Food Effect on the Exposures of Two Formulations of CC 92480 in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Pharmacokinetics- Tmax Part 2
研究概览
简要总结
This is a Phase 1 study that will be conducted in 2 parts. Participants may participate in 1 part only.
- Part 1 will be a randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, and PK of CC-92480-02 (Formulation A) administered orally under fasted conditions in healthy adult participants.
- Part 2 will be a randomized, open-label, 2 × 4 crossover study (Periods 1, 2, 3, and 4) to evaluate the relative bioavailability (RBA) of Formulation A versus Formulation B under fasted conditions and explore safety, tolerability, and PK effects of food on Formulation A and Formulation B in healthy adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must satisfy the following criteria to be enrolled in the study:
- •Must understand and voluntarily sign a written informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
- •Healthy adult female of nonchildbearing potential or male 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 Physical examination (PE).
- •Agrees to abide by the requirements and restrictions outlined in the CC-92480 Pregnancy Prevention Plan for Participants in Clinical Trials.
- •a. Practice true abstinence (which must be reviewed on a monthly basis, as applicable) or agree to use a 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) while on study medication, and for at 3 months after the last dose of study medication even if he has undergone a successful vasectomy.
- •For females:
- •Female participants 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 serum follicle-stimulation hormone (FSH) level of > 40 IU/L at screening.
- •Must have a body mass index between 18 and 33 kg/m2 (inclusive) at the time of signing the ICF.
- •Clinical laboratory test results must be within the respective reference ranges; or if not, the results be clinically insignificant according to the Investigator's medical judgment.
- •Participant must agree and be willing to consume a standard high-fat meal (which may contain gluten), for Part 2 participants only.
排除标准
- •The presence of any of the following will exclude a participant from enrollment:
- •Female of childbearing potential, pregnant, or breastfeeding.
- •History of any clinically significant and relevant neurological, gastrointestinal (GI), renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders as determined by the Investigator.
- •History of severe (eg, anaphylactic, anaphylactoid, Stevens-Johnson, angioedematous) reaction to a drug, or adverse reactions to multiple drugs.
- •Use of any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 28 days of the first dose administration.
- •Use of any nonprescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration.
- •Donation of blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.
- •History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before first dose administration, or positive drug screening test reflecting consumption of illicit drugs.
- •History of alcohol abuse (as defined by the current version of the DSM) within 2 years before first dose administration, or positive alcohol screen.
- •Known to have serum hepatitis or known to be a carrier of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV Ab), or have a reactive result to the test for human immunodeficiency virus (HIV) antibodies at screening.
- •Use of tobacco- or nicotine-containing products within 3 months prior to Day -1, as assessed by medical history and physical examination, or positive urine cotinine test at screening.
- •Vaccination within 30 days of first dose administration or plans to receive vaccination (live and attenuated) within 30 days after dosing.
研究组 & 干预措施
CC-92480-02 (Formulation A) with Placebo
CC-92480-02 (Formulation A) or matching placebo to be administered orally under fasted conditions.
干预措施: CC-92480 (Drug)
CC-92480-02 (Formulation A) with Placebo
CC-92480-02 (Formulation A) or matching placebo to be administered orally under fasted conditions.
干预措施: Placebo (Other)
CC-92480 (Formulation B)- fasted condition
A single oral dose of CC-92480 (Formulation B) administered under fasted conditions.
干预措施: CC-92480 (Drug)
CC-92480-02 (Formulation A) - fasted condition
A single oral dose of CC-92480-02 (Formulation A) administered under fasted conditions.
干预措施: CC-92480 (Drug)
CC-92480 (Formulation B) - Low-fat meal
A single oral dose of CC-92480 (Formulation B) administered under fed conditions (low-fat meal).
干预措施: CC-92480 (Drug)
CC-92480-02 (Formulation A) - high-fat meal
A single oral dose of CC-92480-02 (Formulation A) administered under fed conditions (high-fat meal).
干预措施: CC-92480 (Drug)
结局指标
主要结局
Pharmacokinetics- Tmax Part 2
时间窗: Up to 96 hours after dosing
Time to maximum plasma concentration
Pharmacokinetics- CL/F Part 1
时间窗: Up to 96 hours after dosing
Apparent total plasma clearance
Pharmacokinetics- Cmax Part 1
时间窗: Up to 96 hours after dosing
Maximum plasma concentration of drug
Pharmacokinetics- Tmax Part 1
时间窗: Up to 96 hours after dosing
Time to maximum plasma concentration
Pharmacokinetics- Vz/F Part 1
时间窗: Up to 96 hours after dosing
Apparent volume of distribution
Pharmacokinetics- Ratio of Cmax (Formulation A/Formulation B) Part 2
时间窗: Up to 96 hours after dosing
Ratio of maximum plasma concentration of drug
Pharmacokinetics- t½ Part 1
时间窗: Up to 96 hours after dosing
Terminal elimination half-life
Pharmacokinetics- Cmax Part 2
时间窗: Up to 96 hours after dosing
Maximum plasma concentration of drug
Pharmacokinetics- AUC0-t (Formulation A/Formulation B) Part 2
时间窗: Up to 96 hours after dosing
Area under the plasma concentration-time curve from time zero to the last observable concentration
Pharmacokinetics- t½ Part 2
时间窗: Up to 96 hours after dosing
Terminal elimination half-life
Pharmacokinetics- Vz/F Part 2
时间窗: Up to 96 hours after dosing
Apparent volume of distribution
Pharmacokinetics- AUC0-∞ Part 2
时间窗: Up to 96 hours after dosing
Area under the plasma concentration-time curve from time zero to infinity
Pharmacokinetics- AUC0-t Part 2
时间窗: Up to 96 hours after dosing
Area under the plasma concentration-time curve from time zero to the last observable concentration
Pharmacokinetics- AUC0-∞Part 1
时间窗: Up to 96 hours after dosing
Area under the plasma concentration-time curve from time zero to infinity
Pharmacokinetics- AUC0-t Part1
时间窗: Up to 96 hours after dosing
Area under the plasma concentration-time curve from time zero to the last observable concentration
Pharmacokinetics- tlag Part 1
时间窗: Up to 96 hours after dosing
Lag time between time of administration and start of absorption
Pharmacokinetics- Ratio of AUC0-∞ (Formulation A/Formulation B) Part 2
时间窗: Up to 96 hours after dosing
Ratio of area under the plasma concentration-time curve from time zero to infinity
Pharmacokinetics- CL/F Part 2
时间窗: Up to 96 hours after dosing
Apparent total plasma clearance
Pharmacokinetics- tlag Part 2
时间窗: Up to 96 hours after dosing
Lag time between time of administration and start of absorption
次要结局
- Pharmacokinetics- Tmax (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Cmax (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-∞ (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- CL/F (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- AUC0-∞(high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- t½ (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Vz/F (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- tlag (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Ratio (Fed/Fasted) of Cmax (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-t (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- AUC0-24 (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- AUC0-∞(low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- t½ (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Vz/F (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-t (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-∞(low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- AUC0-t (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Tmax (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Ratio (Fed/Fasted) of Cmax (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- AUC0-t (high-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- Cmax (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- CL/F (low-fat meal)(Up to 96 hours after dosing)
- Pharmacokinetics- tlag (low-fat meal)(Up to 96 hours after dosing)
- Incidence of Adverse Events (AEs)(From enrollment until at least 28 days after completion of study treatment)