Study to Evaluate Pharmacokinetics of Prototype Modified-Release Formulations Of Apremilast in Healthy Men

NCT ID: NCT02236988

Last Updated: 2021-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-07
• Study Completion Date: 2014-09-11

Brief Summary

This study will assess up to 12 different oral formulations of apremilast to determine how much apremilast is absorbed by the body compared to a reference formulation.

Detailed Description

This will be a single-center, open-label, crossover, single modified-release-dose study in adult males to evaluate the pharmacokinetics (PK) of prototype modified-release (MR) formulations compared to the reference immediate-release (IR) apremilast formulation. Within 4 separate groups, participants will be randomly assigned to a treatment sequence. A total of up to 12 test MR formulations may be evaluated.

Group 1: A 4-sequence, 4-period design to compare three modified-release prototypes with the reference immediate-release formulation. A total of 16 participants will be enrolled to obtain at least 12 participants who complete all 4 periods.

Group 2: A 4-sequence, 4-period design to compare three MR prototypes with the reference IR formulation. Sixteen participants will be enrolled to obtain at least 12 participants who complete all four periods.

Group 3: A six-sequence, three-period design to compare two MR prototypes with the reference IR formulation. Eighteen participants will be enrolled to obtain at least 12 participants who complete all three periods.

Group 4: A 10-sequence, 5-period design to compare four MR prototypes with the reference IR formulation. Thirty participants will be enrolled to obtain at least 20 participants who complete all five periods.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Group 1

Participants received the following 4 treatments, given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB) with 7 to 10 days between each treatment:

A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) B) A single oral dose 75 mg apremilast tablet prototype MR 1 C) A single oral dose 75 mg apremilast tablet prototype MR 2 D) A single oral dose 75 mg apremilast capsule prototype MR 3

Group Type: EXPERIMENTAL

Apremilast Immediate Release

Intervention Type: DRUG

30 mg immediate release tablets

Apremilast Modified Release 1

Intervention Type: DRUG

75 mg oral tablet of prototype modified release (MR) 1

Apremilast Modified Release 2

Intervention Type: DRUG

75 mg oral tablet of prototype MR 2

Apremilast Modified Release 3

Intervention Type: DRUG

75 mg oral capsule of prototype MR 3

Group 2

Participants received the following 4 treatments, given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE) with 7 to 10 days between each treatment:

A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) E) A single oral dose 75 mg apremilast capsule prototype MR 4 F) A single oral dose 75 mg apremilast capsule prototype MR 5 G) A single oral dose 75 mg apremilast capsule prototype MR 6

Group Type: EXPERIMENTAL

Apremilast Immediate Release

Intervention Type: DRUG

30 mg immediate release tablets

Apremilast Modified Release 4

Intervention Type: DRUG

75 mg oral capsule of prototype MR 4

Apremilast Modified Release 5

Intervention Type: DRUG

75 mg oral capsule of prototype MR 5

Apremilast Modified Release 6

Intervention Type: DRUG

75 mg oral capsule of prototype MR 6

Group 3

Participants received the following 3 treatments, given in 6 possible sequences (AIJ, IJA, JAI, AJI, IAJ, or JIA) with 7 to 10 days between each treatment:

A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) I) A single oral dose 80 mg apremilast capsule prototype MR 8 J) A single oral dose 80 mg apremilast capsule prototype MR 9

Group Type: EXPERIMENTAL

Apremilast Immediate Release

Intervention Type: DRUG

30 mg immediate release tablets

Apremilast Modified Release 8

Intervention Type: DRUG

80 mg oral capsule of prototype MR 8

Apremilast Modified Release 9

Intervention Type: DRUG

80 mg oral capsule of prototype MR 9

Group 4

Participants received the following 5 treatments, given in 10 possible sequences (ALOMN, LMANO, MNLOA, NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, or MLNAO) with 7 to 10 days between each treatment:

A) Two oral doses of 30 mg apremilast immediate release tablets 12 hours apart (reference formulation) L) A single oral dose 80 mg apremilast capsule prototype MR 11 M) A single oral dose 80 mg apremilast capsule prototype MR 12 N) A single oral dose 80 mg apremilast capsule prototype MR 13 O) A single oral dose 80 mg apremilast capsule prototype MR 14

Group Type: EXPERIMENTAL

Apremilast Immediate Release

Intervention Type: DRUG

30 mg immediate release tablets

Apremilast Modified Release 11

Intervention Type: DRUG

80 mg oral capsule of prototype MR 11

Apremilast Modified Release 12

Intervention Type: DRUG

80 mg oral capsule of prototype MR 12

Apremilast Modified Release 13

Intervention Type: DRUG

80 mg oral capsule of prototype MR 13

Apremilast Modified Release 14

Intervention Type: DRUG

80 mg oral capsule of prototype MR 14

Interventions

Apremilast Immediate Release

30 mg immediate release tablets

Intervention Type: DRUG

Apremilast Modified Release 1

75 mg oral tablet of prototype modified release (MR) 1

Intervention Type: DRUG

Apremilast Modified Release 2

75 mg oral tablet of prototype MR 2

Intervention Type: DRUG

Apremilast Modified Release 3

75 mg oral capsule of prototype MR 3

Intervention Type: DRUG

Apremilast Modified Release 4

75 mg oral capsule of prototype MR 4

Intervention Type: DRUG

Apremilast Modified Release 5

75 mg oral capsule of prototype MR 5

Intervention Type: DRUG

Apremilast Modified Release 6

75 mg oral capsule of prototype MR 6

Intervention Type: DRUG

Apremilast Modified Release 8

80 mg oral capsule of prototype MR 8

Intervention Type: DRUG

Apremilast Modified Release 9

80 mg oral capsule of prototype MR 9

Intervention Type: DRUG

Apremilast Modified Release 11

80 mg oral capsule of prototype MR 11

Intervention Type: DRUG

Apremilast Modified Release 12

80 mg oral capsule of prototype MR 12

Intervention Type: DRUG

Apremilast Modified Release 13

80 mg oral capsule of prototype MR 13

Intervention Type: DRUG

Apremilast Modified Release 14

80 mg oral capsule of prototype MR 14

Intervention Type: DRUG

Other Intervention Names

Otezla; CC-10004

Eligibility Criteria

Inclusion Criteria

Subjects must satisfy ALL of the following criteria to be eligible for enrollment into the study:

1. Must understand and voluntarily sign a written informed consent form prior to any study-related 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. Male subjects of any race between 18 to 55 years of age (inclusive), and in good health as determined by the Investigator.

4. Has a body mass index between 18 and 33 kg/m^2 (inclusive).

5. No clinically significant laboratory tests as determined by the investigator.

6. Must not have a fever, with systolic blood pressure: 90 to 140 mmHg and diastolic blood pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm (measurements taken while lying down).

7. Must have a normal or clinically acceptable 12-lead electrocardiogram (ECG).

8. Subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or non-latex condom not made out of natural [animal] membrane [eg, polyurethane]) while on study medication, and for 28 days after the last dose of study medication.

9. Must agree to refrain from donating sperm, blood or plasma (other than for this study) while participating in this study and for at least 28 days after the last dose of study drug.

Exclusion Criteria

The presence of ANY of the following will exclude any healthy subject from enrollment into the study:

1. History of any clinically significant and relevant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders.

2. Any condition which places the subject at unacceptable risk if he 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 within 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 14 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, eg, bariatric procedure, colon resection, irritable bowel syndrome, Crohn's disease, etc. Subjects with cholecytectomy and appendectomy may be included.

6. Exposure to an investigational drug (new chemical entity) 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 within 8 weeks before the first dose administration to a blood bank or blood donation center.

8. History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual (DSM) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.

9. History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or a positive alcohol screen.

10. Known to have serum hepatitis, or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody, or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at Screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Covance Clinical Research Unit Inc.

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

CC-10004-CP-027

Identifier Type: -

Identifier Source: org_study_id