Clinical trial NCT02433457: Relative Bioavailability Study of CC-292
Official title: An Open-label, Phase 1, Randomized, Seven-treatment, Seven-period, Crossover Study to Assess the Relative Bioavailability, pH Effect, Food Effect and Dose Proportionality of CC-292 Spray Dried Dispersion Formulation in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Healthy Volunteers
CC-292
Open-Label
Bioavailability Pharmacokinetics
Phase I
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2015-05-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To evaluate the PK profile of the newly developed CC-292 SDD formulation compared to CC-292 P22 tablet.

Detailed description: This is a single center, open-label, randomized, seven-treatment, seven-period, crossover design. The study will consist of a screening phase, a treatment phase, and a follow-up phone call. Approximately 24 healthy adult subjects (male or female) will be enrolled.

Eligibility criteria: Inclusion Criteria:

1. Must understand and voluntarily sign a written Informed Consent Form (ICF) prior to any study-related assessments/procedures being conducted.
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. Must be a male or female subject from any race between 18 to 65 years of age (inclusive) at the time of signing the ICF, and in good health as determined by Physical Examinations (PE).
4. Must comply with the following acceptable forms of contraception:

   1. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception with male condoms NOT made out of natural animal membrane (e.g., latex or polyurethane condoms are acceptable) while on study drug, and for at least 90 days after the last dose of study drug.
   2. Females of childbearing potential (FCBP) 1 must have a negative pregnancy test at Screening and at Baseline (i.e., on Day -1). FCBP who engage in activity in which conception is possible must agree to use one of the following forms of contraception during their entire participation in the study and for at least 30 days after administration of the last dose of study drug:

      * Option 1: Any one of the following: non-oral hormonal contraception (e.g., injection, implant, transdermal patch, vaginal ring); intrauterine device; tubal ligation; or a partner with a vasectomy; OR
      * Option 2: Oral contraceptive pills PLUS one additional barrier method of the following: (a) male or female condom NOT made out of natural animal membrane (e.g., latex or polyurethane is acceptable); (b) diaphragm with spermicide; (c) cervical cap with spermicide; or (d) contraceptive sponge with spermicide; OR
      * Option 3: TWO of the following barrier methods: (a) male or female condom NOT made out of natural animal membrane (e.g., latex or polyurethane is acceptable); (b) diaphragm with spermicide; (c) cervical cap with spermicide; or (d) a contraceptive sponge with spermicide.

   Note: All other females must have been surgically sterilized for at least 6 months before Screening (proper documentation required), or be postmenopausal (defined as 24 months without menses before Screening, and an estradiol level of \< 30 pg/mL and a plasma Follicle Stimulating Hormone (FSH) level \> 40 IU/L at Screening).
5. Must have a Body Mass Index (BMI) between 18 and 33 kg/m2 (inclusive).
6. No clinically significant laboratory test results, as determined by the Investigator.
7. Must be afebrile, with supine systolic BP of 90 to 140 mmHg, a supine diastolic Blood Pressure (BP) of 60 to 90 mmHg, and pulse rate of 40 to 110 bpm.
8. Must have a normal or clinically acceptable 12-lead Electrocardiogram (ECG) at Screening. Male subjects must have a QTcF value ≤ 430 msec. Female subjects must have a QTcF value ≤ 450 msec.

Exclusion Criteria:

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/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 antibiotics, analgesics, anesthetics, etc.) prior to 30 days of the first dose administration, unless Sponsor agreement is obtained.
4. Use of any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 7 days of the first dose administration, unless Sponsor agreement is obtained.
5. Any surgical or medical condition possibly affecting drug absorption, distribution, metabolism and excretion (e.g., bariatric procedure), or plans to have elective or medical procedures during the conduct of the trial. Subjects post cholecystectomy and post appendectomy may be included.
6. Exposure to an investigational drug within 30 days prior to the first dose administration or 5 half-lives of that investigational drug, if known (whichever is longer).
7. Donated blood or plasma prior to 4 weeks before the first dose administration to a blood bank or blood donation center.
8. History of multiple drug allergies (i.e., two or more);
9. History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM\]) prior to 2 years before first dose administration, or a positive drug screen reflecting consumption of illicit drugs.
10. History of alcohol abuse (as defined by the current version of the DSM) prior to 2 years before dosing, or a positive alcohol screen.
11. Known to have hepatitis, or known to be a carrier of the Hepatitis B Surface Antigen (HBsAg), or Hepatitis C Virus Antibody (HCVAb), or have a positive result to the test for HBsAg, HCVAb, or Human Immunodeficiency Virus (HIV) antibodies at Screening.
12. History of smoking or the use of nicotine containing products prior to 3 months of Screening by self reporting.
13. Female subjects lactating or breastfeeding a child.

Primary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: 48 hours
measure: Pharmacokinetics - AUC 0-t
timeFrame: 48 hours
measure: Pharmacokinetics - AUC 0-24
timeFrame: 48 hours
measure: Pharmacokinetics - AUC 0-∞
timeFrame: 48 hours
measure: Pharmacokinetics - %AUCextrap
timeFrame: 48 hours
measure: Pharmacokinetics - Frel
timeFrame: 48 hours
measure: Pharmacokinetics - Tmax
timeFrame: 48 hours
measure: Pharmacokinetics - λz
timeFrame: 48 hours
measure: Pharmacokinetics - t1/2
timeFrame: 48 hours
measure: Pharmacokinetics - CL/F
timeFrame: 48 hours
measure: Pharmacokinetics - Vz/F
timeFrame: 48 hours
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Approximatly 52 days
Other outcomes:
Locations:
city: Evansville
country: United States
facility: Covance Clinical Research unit
state: Indiana
Study officials:
affiliation: Celgene Corporation
name: Daniel Weiss, MD
role: STUDY_DIRECTOR
References:
citation: Cheng Y, Liu L, Xue Y, Zhou S, Li Y. An Open Label, Phase 1, Randomized, Seven-treatment, Seven-period, Crossover Study to Assess the Relative Bioavailability, pH Effect, Food Effect, and Dose Proportionality of CC-292, a Potent and Orally Available Bruton's Tyrosine Kinase Inhibitor. Eur J Drug Metab Pharmacokinet. 2022 Jul;47(4):579-592. doi: 10.1007/s13318-022-00776-7. Epub 2022 Jun 3.