A Phase I, Randomized, Single-center, 3-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of CC 99677 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- CC-99677
- Conditions
- Healthy Volunteer
- Sponsor
- Celgene
- Enrollment
- 97
- Locations
- 1
- Primary Endpoint
- Adverse Events (AEs)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a phase 1, randomized, single-center, 3-part, FIH study to assess the safety, tolerability, pharmacokinetics (PK, or how the drug behaves in the body), and pharmacodynamics (PD, or what the drug does to the body) of single and multiple doses of CC-99677 and to characterize the effect of food on the single-dose PK of CC-99677 in healthy adult subjects.
Detailed Description
This first-in-human (FIH) study aims to identify a safe and tolerable dose of CC 99677 in support of phase 2 and/or phase 3 studies to be conducted in subjects with underlying inflammatory diseases. The study also aims to evaluate the PK of CC-99677 following administration of single and multiple oral doses, including assessment of the effect of food on the single dose PK of CC 99677, and to assess the effect of CC 99677 on electrocardiogram (ECG) parameters in healthy adult subjects. The pharmacodynamics (PD) and pharmacogenomics (PG) of CC 99677 will also be assessed. Parts 1 and 2 are designed to evaluate the safety, tolerability, PK, and PD of single and multiple ascending doses of CC 99677, respectively. The study has been designed to allow for safety, tolerability, and PK data to be gathered in a stepwise fashion. Part 1 will consist of escalating single doses in sequential groups. Approximately 48 subjects will be enrolled into 6 planned dose level cohorts. Part 2 will consist of escalating multiple doses (administered for 14 days) in sequential groups. In Part 2, approximately 40 subjects will be enrolled into 5 proposed dose level cohorts. Each dose level cohort will consist of 8 subjects; 6 subjects will receive CC-99677 and 2 subjects will receive placebo according to the randomization schedule. In both Part 1 and Part 2, a higher daily dose level will not be initiated until adequate information on the preceding dose level is available and reviewed. Parts 1 and 2 will also employ strict dose escalation, individual subject, and intra cohort stopping criteria. Parts 1 and 2 will be placebo controlled to appropriately characterize the safety and tolerability of CC 99677. Part 3 is designed to characterize the effect of food on the single dose PK of CC 99677.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must satisfy the following criteria to be enrolled in the study:
- •Subject is ≥ 18 and ≤ 55 years of age at the time of signing the informed consent form (ICF).
- •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) must:
- •Have 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 FCBP subject practices true abstinence from heterosexual contact.
- •Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis, as applicable, and source documented) or agree to use, and be able to comply with, one highly effective method and one effective barrier method of contraception without interruption, during the study (including any dose interruptions), and for at least 30 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, hormonal contraception should be initiated at least 28 days prior to enrollment).
- •Female subjects NOT of childbearing potential must:
- •Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation is required) at least 6 months before screening, or be postmenopausal (defined as 24 consecutive months without menses before screening, with a follicle-stimulating hormone \[FSH\] level of \> 40 IU/L at screening).
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.
- •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.
- •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.
- •Subject has used CYP3A inducers and/or inhibitors (including St. John's Wort) within 30 days preceding the first dose administration. The Indiana University (2016) "Cytochrome P450 Drug Interaction Table" should be utilized to determine inducers and/or inhibitors of CYP3A (http://medicine.iupui.edu/clinpharm/ddis/table.aspx). The Sponsor's Medical Monitor or designee should be queried in case of uncertainty.
Arms & Interventions
CC-99677 Under Fasted Conditions
CC-99677 Under Fasted Conditions
Intervention: CC-99677
Placebo
Placebo under fasted conditions
Intervention: Placebo
CC-99677 Under Fed Conditions
CC-99677 Under Fed Conditions
Intervention: CC-99677
Outcomes
Primary Outcomes
Adverse Events (AEs)
Time Frame: From enrollment until at least 28 days after completion of treatment
Number of subjects with adverse events
Secondary Outcomes
- Pharmacokinetics - Tmax(up to 28 days)
- Pharmacokinetics - t1/2,z(up to 28 days)
- Pharmacokinetics - AUC0-∞(up to 28 days)
- Pharmacokinetics - Cmax(up to 28 days)
- Pharmacokinetics - AUC0-t(up to 28 days)
- Pharmacokinetics - Vz/F(up to 28 days)
- Effect of CC-99677 on electrocardiogram (ECG) parameters(up to 24 hours after single dose administration)
- Pharmacokinetics - CL/F(up to 28 days)