Relative Bioavailability and PPI Effects of CC-92480 Test and Reference Formulations in Healthy Subjects

A Phase 1, Open-label Study to Assess the Single Dose Pharmacokinetics and Relative Bioavailability of a Test Capsule Formulation of CC-92480 Compared to a Reference CC 92480 Capsule Formulation and the Effect of a Proton Pump Inhibitor on the Pharmacokinetics of CC 92480 From Test and Reference Formulations in Healthy Subjects

This is a Phase 1, open-label, randomized, four-period, crossover study in healthy females of nonchildbearing potential and male subjects - to be conducted at a single center in the United States.

The study will consist of a screening phase, a baseline phase, four treatment periods, and a follow-up phone call. The 4 treatment periods are divided into two pairs (Period 1 and 2 and Period 3 and 4), potentially separated by an intermission during which subjects will be discharged from the research unit: Periods 1 and 2 support relative bioavailability (RBA) estimation, while Periods 3 and 4 support estimation of PPI effects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: CC-92480; Drug: Rabeprazole

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Phase 1 Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

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. Healthy adult male or female 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. For males:

   1. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 3 months following investigational product discontinuation, even if he has undergone a successful vasectomy.
   2. 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 3 months after the last dose of study medication.
5. Must have a body mass index between 18 and 33 kg/m2 (inclusive) at the time of signing the ICF.
6. 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 judgement.

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. 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).
3. Use of tobacco - or nicotine-containing products within 3 months prior to Day -1 (Period 1 for Part 2).
4. Vaccination within 30 days of first dose administration or plans to receive vaccination within 30 days after dosing.
5. Subjects with active hepatitis and HIV
6. Use of any nonprescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration.
7. Use of CYP3A inducers and inhibitors (including St. John's Wort) within 30 days of the first dose administration.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of CC-92480 and Rabeprazole; Test Formulation CC-92480 and Reference Formulation will be administered orally at 1.6 mg. Rabeprazole will be administered orally at 40 mg.	Drug: CC-92480; CC-92480; Drug: Rabeprazole; Rabeprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - AUC0-∞ (Reference Formulation)	Area under the plasma concentration-time curve from time zero to infinity	Up to 5 days
Pharmacokinetics - AUC0-∞ (Test Formulation)	Area under the plasma concentration-time curve from time zero to the last observable concentration at time t	Up to 5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject 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 subject's health, including laboratory test values (as specified by the criteria in Section 10.3), 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.	From enrollment until at least 28 days after completion of study treatment
Pharmacokinetics -Cmax (Reference Formulation)	Maximum plasma concentration	Day 1
Pharmacokinetics - Cmax (Test Formulation)	Maximum plasma concentration	Day 1
Pharmacokinetics - AUC0-t (Reference Formulation)	Area under the plasma concentration-time curve from time zero to the last observable concentration at time t	Up to 5 days
Pharmacokinetics - AUC0-t (Test Formulation)	Area under the plasma concentration-time curve from time zero to the last observable concentration at time t	Up to 5 days
Pharmacokinetics -Tmax (Reference Formulation)	Time to peak (maximum) plasma concentration	Day 1
Pharmacokinetics -Tmax (Test Formulation)	Time to peak (maximum)plasma concentration	Day 1
Pharmacokinetics - CL/F (Reference Formulation)	Apparent total plasma clearance	Up to 5 days
Pharmacokinetics - CL/F (Test Formulation)	Apparent total plasma clearance	Up to 5 days
Pharmacokinetics - Vz/F (Reference Formulation)	Apparent volume of distribution	Up to 5 days
Pharmacokinetics - Vz/F (Test Formulation)	Apparent volume of distribution	Up to 5 days
Pharmacokinetics - t1/2 (Reference Formulation)	Terminal elimination half-life	Up to 5 days
Pharmacokinetics - t1/2 (Test Formulation)	Terminal elimination half-life	Up to 5 days

Collaborators and Investigators

• Sponsor: Celgene

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2019
• Primary Completion (Actual): December 26, 2019
• Study Completion (Actual): December 26, 2019

Study Registration Dates

• First Submitted: December 24, 2019
• First Submitted That Met QC Criteria: December 24, 2019
• First Posted (Actual): December 26, 2019

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Subjects; CC-92480
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Rabeprazole
• Other Study ID Numbers: CC-92480-CP-002; U1111-1242-7394 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No