A Study to Assess Safety, Tolerability, and Pharmacokinetics of CC-92480 Formulations in Healthy Adult Participants

• Sponsor: Celgene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04839809
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 5
• Actual Duration (Months): 8.6
• Patients Per Site Per Month: 4.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: CC-92480; Other: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jan 19, 2021
• Actual Primary Completion Date: Oct 8, 2021
• Actual Study Completion Date: Oct 8, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CC-92480-02 (Formulation A) with Placebo CC-92480-02 (Formulation A) or matching placebo to be administered orally under fasted conditions.	Drug: CC-92480; Oral; Other: Placebo; Oral
Experimental: CC-92480 (Formulation B)- fasted condition A single oral dose of CC-92480 (Formulation B) administered under fasted conditions.	Drug: CC-92480; Oral
Experimental: CC-92480-02 (Formulation A) - fasted condition A single oral dose of CC-92480-02 (Formulation A) administered under fasted conditions.	Drug: CC-92480; Oral
Experimental: CC-92480 (Formulation B) - Low-fat meal A single oral dose of CC-92480 (Formulation B) administered under fed conditions (low-fat meal).	Drug: CC-92480; Oral
Experimental: 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).	Drug: CC-92480; Oral

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics- Cmax Part 1 [Up to 96 hours after dosing]

   Maximum plasma concentration of drug

2. Pharmacokinetics- Tmax Part 1 [Up to 96 hours after dosing]

   Time to maximum plasma concentration

3. Pharmacokinetics- AUC0-∞Part 1 [Up to 96 hours after dosing]

   Area under the plasma concentration-time curve from time zero to infinity

4. Pharmacokinetics- AUC0-t Part1 [Up to 96 hours after dosing]

   Area under the plasma concentration-time curve from time zero to the last observable concentration

5. Pharmacokinetics- t½ Part 1 [Up to 96 hours after dosing]

   Terminal elimination half-life

6. Pharmacokinetics- CL/F Part 1 [Up to 96 hours after dosing]

   Apparent total plasma clearance

7. Pharmacokinetics- Vz/F Part 1 [Up to 96 hours after dosing]

   Apparent volume of distribution

8. Pharmacokinetics- tlag Part 1 [Up to 96 hours after dosing]

   Lag time between time of administration and start of absorption

9. Pharmacokinetics- Cmax Part 2 [Up to 96 hours after dosing]

   Maximum plasma concentration of drug

10. Pharmacokinetics- Ratio of Cmax (Formulation A/Formulation B) Part 2 [Up to 96 hours after dosing]

    Ratio of maximum plasma concentration of drug

11. Pharmacokinetics- AUC0-∞ Part 2 [Up to 96 hours after dosing]

    Area under the plasma concentration-time curve from time zero to infinity

12. Pharmacokinetics- Ratio of AUC0-∞ (Formulation A/Formulation B) Part 2 [Up to 96 hours after dosing]

    Ratio of area under the plasma concentration-time curve from time zero to infinity

13. Pharmacokinetics- AUC0-t Part 2 [Up to 96 hours after dosing]

    Area under the plasma concentration-time curve from time zero to the last observable concentration

14. Pharmacokinetics- AUC0-t (Formulation A/Formulation B) Part 2 [Up to 96 hours after dosing]

    Area under the plasma concentration-time curve from time zero to the last observable concentration

15. Pharmacokinetics- Tmax Part 2 [Up to 96 hours after dosing]

    Time to maximum plasma concentration

16. Pharmacokinetics- t½ Part 2 [Up to 96 hours after dosing]

    Terminal elimination half-life

17. Pharmacokinetics- CL/F Part 2 [Up to 96 hours after dosing]

    Apparent total plasma clearance

18. Pharmacokinetics- Vz/F Part 2 [Up to 96 hours after dosing]

    Apparent volume of distribution

19. Pharmacokinetics- tlag Part 2 [Up to 96 hours after dosing]

    Lag time between time of administration and start of absorption

Secondary Outcome Measures

1. Pharmacokinetics- Cmax (high-fat meal) [Up to 96 hours after dosing]

   Maximum plasma concentration of drug

2. Pharmacokinetics- Ratio (Fed/Fasted) of Cmax (high-fat meal) [Up to 96 hours after dosing]

   Ratio of maximum plasma concentration of drug

3. Pharmacokinetics- AUC0-∞(high-fat meal) [Up to 96 hours after dosing]

   Area under the plasma concentration-time curve from time zero to infinity

4. Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-∞ (high-fat meal) [Up to 96 hours after dosing]

   Ratio of area under the plasma concentration-time curve from time zero to infinity

5. Pharmacokinetics- AUC0-t (high-fat meal) [Up to 96 hours after dosing]

   Area under the plasma concentration-time curve from time zero to the last observable concentration

6. Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-t (high-fat meal) [Up to 96 hours after dosing]

   Ratio of area under the plasma concentration-time curve from time zero to the last observable concentration

7. Pharmacokinetics- Tmax (high-fat meal) [Up to 96 hours after dosing]

   Time to maximum plasma concentration

8. Pharmacokinetics- AUC0-24 (high-fat meal) [Up to 96 hours after dosing]

   Area under the plasma concentration-time curve from time zero to 24 hours post dose

9. Pharmacokinetics- t½ (high-fat meal) [Up to 96 hours after dosing]

   Terminal elimination half-life

10. Pharmacokinetics- CL/F (high-fat meal) [Up to 96 hours after dosing]

    Apparent total plasma clearance

11. Pharmacokinetics- Vz/F (high-fat meal) [Up to 96 hours after dosing]

    Apparent volume of distribution

12. Pharmacokinetics- tlag (high-fat meal) [Up to 96 hours after dosing]

    Lag time between time of administration and start of absorption

13. Pharmacokinetics- Cmax (low-fat meal) [Up to 96 hours after dosing]

    Maximum plasma concentration of drug

14. Pharmacokinetics- Ratio (Fed/Fasted) of Cmax (low-fat meal) [Up to 96 hours after dosing]

    Ratio of maximum plasma concentration of drug

15. Pharmacokinetics- AUC0-∞(low-fat meal) [Up to 96 hours after dosing]

    Area under the plasma concentration-time curve from time zero to infinity

16. Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-∞(low-fat meal) [Up to 96 hours after dosing]

    Ratio of area under the plasma concentration-time curve from time zero to infinity

17. Pharmacokinetics- AUC0-t (low-fat meal) [Up to 96 hours after dosing]

    Area under the plasma concentration-time curve from time zero to the last observable concentration

18. Pharmacokinetics- Ratio (Fed/Fasted) of AUC0-t (low-fat meal) [Up to 96 hours after dosing]

    Ratio of area under the plasma concentration-time curve from time zero to the last observable concentration

19. Pharmacokinetics- Tmax (low-fat meal) [Up to 96 hours after dosing]

    Time to maximum plasma concentration

20. Pharmacokinetics- t½ (low-fat meal) [Up to 96 hours after dosing]

    Terminal elimination half-life

21. Pharmacokinetics- CL/F (low-fat meal) [Up to 96 hours after dosing]

    Apparent total plasma clearance

22. Pharmacokinetics- Vz/F (low-fat meal) [Up to 96 hours after dosing]

    Apparent volume of distribution

23. Pharmacokinetics- tlag (low-fat meal) [Up to 96 hours after dosing]

    Lag time between time of administration and start of absorption

24. Incidence of Adverse Events (AEs) [From enrollment until at least 28 days after completion of study treatment]

    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Participants 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 conducted.

2. 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).

3. Agrees to abide by the requirements and restrictions outlined in the CC-92480 Pregnancy Prevention Plan for Participants in Clinical Trials.

4. For males:

1. 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.

1. 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.

1. Must have a body mass index between 18 and 33 kg/m2 (inclusive) at the time of signing the ICF.

2. 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.

3. Participant must agree and be willing to consume a standard high-fat meal (which may contain gluten), for Part 2 participants only.

Exclusion Criteria:

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

1. Female of childbearing potential, pregnant, or breastfeeding.

2. 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.

3. History of severe (eg, anaphylactic, anaphylactoid, Stevens-Johnson, angioedematous) reaction to a drug, or adverse reactions to multiple drugs.

4. Use of any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 28 days of the first dose administration.

5. Use of any nonprescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration.

6. Donation of blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.

7. 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.

8. History of alcohol abuse (as defined by the current version of the DSM) within 2 years before first dose administration, or positive alcohol screen.

9. 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.

10. 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.

11. Vaccination within 30 days of first dose administration or plans to receive vaccination (live and attenuated) within 30 days after dosing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PPD Phase 1 Clinic	Austin	Texas	United States	78744

Sponsors and Collaborators

• Celgene

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT04839809
• Other Study ID Numbers: CC-92480-CP-003
• First Posted: Apr 9, 2021
• Last Update Posted: Dec 10, 2021
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Celgene: Healthy Volunteers; CC-92480; Pharmacokinetics

Study Results

No Results Posted as of Dec 10, 2021