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Study to Evaluate Pharmacokinetics of Apremilast in Heatlhy Male Subjects

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ClinicalTrials.gov Identifier: NCT02236988
Recruitment Status : Completed
First Posted : September 11, 2014
Last Update Posted : March 28, 2016
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation

Brief Summary:
To study how the body absorbs apremilast, and how this absorption is affected when the drug is given as different formulations. Blood samples will be taken to look at the amount of study drug in the blood to determine how much apremilast is absorbed by the body. This study is beng done to iddentify the best tablet formulation (preparation) of apremilast.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Apremilast Phase 1

Detailed Description:

This will be a single-center, open-label, crossover, single modified-release-dose, study in male subjects to evaluate the pharmacokinetics of prototype modified-release formulations compared to the reference immediate-release apremilast formulation. Subjects will be randomly assigned to a treatment sequence. A total of up to 8 test MR formulations may be evaluated.

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

One of two scenarios will be conducted in the second group depending on the availability of the modified-release formulations.

This will be a single-center, open-label, crossover, single modified-release-dose, study in male subjects to evaluate the pharmacokinetics of prototype modified-release formulations compared to the reference immediate-release apremilast formulation. Subjects will be randomly assigned to a treatment sequence. A total of up to 8 test MR formulations may be evaluated.

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

One of two scenarios will be conducted in the second group depending on the availability of the modified-release formulations.

Group 2/Scenario 1: This is a 4-sequence, 4-period design identical to Group 1. This will occur if all three modified-release formulations planned for Group 2 are available. A total of 16 subjects will be enrolled to obtain at least 12 subjects who complete all 4 periods.

Group 2/Scenario 2: This is a 6-sequence, 3-period design. This will occur if only two modified-release formulations are tested in Group 2. A total of 18 subjects will be enrolled to obtain at least 12 subjects who complete all 3 periods.

A third group may be enrolled to evaluate the pharmacokinetics of one or two additional prototype formulations (after the initial six) compared to the immediate-release formulation. One of two scenarios will be conducted in the third group depending on the availability of the prototype formulations.

Group 3/Scenario 1: This is a 2-sequence, 2-period design that will be used if one test formulation is available. A total of 14 subjects will be enrolled to obtain at least 12 subjects who complete both periods.

Group 3/Scenario 2: This is a 6-sequence, 3-period design identical to Group 2/Scenario 2 above. This will occur if two test formulations are available. A total of 18 subjects will be enrolled to obtain at least 12 subjects who complete all 3 periods.

A fourth group may be enrolled to evaluate the PK of four additional prototype formulations compared to the IR formulation.

Group 4: This is a 10-sequence, 5-period William Square design to compare four MR prototypes with the reference IR formulation. A total of 30 subjects will be enrolled to obtain at least 20 subjects who complete all 5 periods.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Official Title: A Phase 1, Open-Label, Single Center Study to Evaluate the Pharmacokinetics of Prototype Modified-Release Formulations Of Apremilast (CC-10004) in Healthy Male Subjects
Study Start Date : January 2014
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Apremilast

Arm Intervention/treatment
Experimental: Formulation of apremilast + test formulations 1, 2, and 3
A single oral 60 mg reference formulation of apremilast, given as 30 mg twice a day (BID), and single oral doses of 75 mg of each test formulation numbers 1, 2, and 3 given in 4 possible sequences (ADBC, BACD, CBDA, and DCAB). Each subject will be randomly assigned to a sequence which will determine the order in which each formulation is given. There will be at least 7, and not more than 10 days between each dose
Drug: Apremilast
Other Names:
  • Otezla
  • CC-10004

Experimental: Formulation of apremilast + test formulations 4, 5, and 6
A single oral 60 mg reference formulation (given as 30 mg twice a day),and single oral doses of 75 mg of each test formulation #s 4, 5, and 6 given in 4 possible sequences (AGEF, EAFG, FEGA, and GFAE). Each subject will be randomly assigned to a sequence which will determine the order in which each formulation is given. There will be at least 7, and not more than 10 days between each dose. If only 2 test formulations are available, there will be 6 possible sequences (AEF, EFA, FAE, AFE, EAF, FEA).
Drug: Apremilast
Other Names:
  • Otezla
  • CC-10004

Experimental: Formulation of apremilast + test formulations: 7 and 8
A single oral 60 mg reference formulation (given as 30 mg twice a day),and single oral doses of 75 mg of each test formulation #s 7 and 8 given in 6 possible sequences (AHI, HIA, IAH, AIH, HAI, and IHA). Each subject will be randomly assigned to a sequence which will determine the order in which each formulation is given. If only 1 test formulation is available, there will be 2 possible sequences (AH and HA).
Drug: Apremilast
Other Names:
  • Otezla
  • CC-10004

Experimental: Formulation of Apremilast + test formulations: 11, 12, 13, 14
A single oral 60 mg reference formulation (given as 30 mg twice a day),and single oral doses of 75 mg of each test formulation #s 11, 12, 13, and 14 given in 10 possible sequences (ALOMN, LMANO, MNLOA,NOMAL, OANLM, NMOLA, ONAML, AOLNM, LAMON, and MLNAO). Each subject will be randomly assigned to a sequence which will determine the order in which each formulation is given. There will be at least 7, and not more than 10 days between each dose.
Drug: Apremilast
Other Names:
  • Otezla
  • CC-10004




Primary Outcome Measures :
  1. Pharmacokinetics (PK): Cmax [ Time Frame: Approximately 8 weeks for Groups 1 &2/scenario 1; approximately 6 weeks for Group 2/scenario 2, approximately 5-6 weeks for Group 3 ]
    Observed maximum plasma or serum concentration

  2. PK: AUC0-t [ Time Frame: Approximately 8 weeks for Groups 1 &2/scenario 1; approximately 6 weeks for Group 2/scenario 2, approximately 5-6 weeks for Group 3 ]
    Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point

  3. PK: Area Under the Curve - Infinity AUC0-∞ [ Time Frame: Approximately 8 weeks for Groups 1 &2/scenario 1; approximately 6 weeks for Group 2/scenario 2, approximately 5-6 weeks for Group 3 ]
    Area under the plasma concentration-time curve from time zero extrapolated to infinity

  4. PK: Terminal Half Life [ Time Frame: Approximately 8 weeks for Groups 1 &2/scenario 1; approximately 6 weeks for Group 2/scenario 2, approximately 5-6 weeks for Group 3 ]
    Estimate of the terminal elimination half-life in plasma

  5. PK: T max [ Time Frame: Approximately 8 weeks for Groups 1 &2/scenario 1; approximately 6 weeks for Group 2/scenario 2, approximately 5-6 weeks for Group 3 ]
    Time to Cmax

  6. PK: CL/F [ Time Frame: Approximately 8 weeks for Groups 1 &2/scenario 1; approximately 6 weeks for Group 2/scenario 2, approximately 5-6 weeks for Group 3 ]
    Apparent total plasma or serum clearance of drug after oral administration


Secondary Outcome Measures :
  1. Number and incidence of Adverse Events (AE) [ Time Frame: From the time the subject signs the ICF through 28 days after the last dose of study drug; Up to 8 weeks ]
    An adverse event (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, regardless of etiology.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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/m2 (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 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 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 HBsAg, or HCV Ab, or have a positive result to the test for HIV antibodies at Screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02236988


Locations
United States, Wisconsin
Covance Clinical Research Unit Inc.
Madison, Wisconsin, United States, 53704-2526
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Daniel Weiss, MD Celgene Corporation

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT02236988     History of Changes
Other Study ID Numbers: CC-10004-CP-027
First Posted: September 11, 2014    Key Record Dates
Last Update Posted: March 28, 2016
Last Verified: March 2016

Keywords provided by Celgene Corporation:
Apremilast
Healthy male subjects
Pharmacokinetics

Additional relevant MeSH terms:
Apremilast
Thalidomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents