A Phase 1 Open-Label Study to Evaluate the Effect of CYP450 and P-gp Inhibition and Induction on the Pharmacokinetics of Pomalidomide (CC-4047) in Healthy Male Subjects (DDI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01707407
First received: October 12, 2012
Last updated: December 3, 2012
Last verified: November 2012
  Purpose
  1. To evaluate the pharmacokinetics (PK) of pomalidomide administered with the CYP3A4/P-gp inhibitor ketoconazole compared with pomalidomide alone in healthy male subjects.
  2. To evaluate the PK of pomalidomide administered with the CYP3A4/P-gp inhibitor ketoconazole plus the CYP1A2 inhibitor fluvoxamine compared with pomalidomide alone in healthy male subjects.
  3. To assess the PK of pomalidomide administered with the CYP1A2 inhibitor fluvoxamine and the CYP3A4/P-gp inhibitor ketoconazole compared with pomalidomide plus the CYP3A4/P-gp inhibitor ketoconazole in healthy male subjects.

Part 2

1) To evaluate the pharmacokinetics of pomalidomide administered with the CYP3A4 inducer carbamazepine compared with pomalidomide alone in healthy male volunteers.

Secondary Objectives

1) To evaluate the safety of pomalidomide in Part 1 and Part 2 when administered with ketoconazole, fluvoxamine and/or carbamazepine.

In addition: To evaluate the safety of pomalidomide in Part 1 and Part 2 when administered with ketoconazole, fluvoxamine and/or carbamazepine.


Condition Intervention Phase
Pharmacology, Clinical
Healthy
Drug: Pomalidomide
Drug: Ketoconazole
Drug: Fluvoxamine
Drug: Carbamazepine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase 1 Open-Label Study to Evaluate the Effect of CYP450 and P-gp Inhibition and Induction on the Pharmacokinetics of Pomalidomide (CC-4047) in Healthy Male Subjects

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • PK-Cmax [ Time Frame: Up to 13 days ] [ Designated as safety issue: No ]
    Cmax-Maximum observed concentration in plasma

  • PK-Tmax [ Time Frame: Up to 13 days ] [ Designated as safety issue: No ]
    Tmax: Time to maximum concentration

  • PK-AUC [ Time Frame: Up to 13 days ] [ Designated as safety issue: No ]
    AUC-Area under the plasma concentration-time curve

  • PK-(T1/2) [ Time Frame: Up to 13 days ] [ Designated as safety issue: No ]
    T1/2-Terminal half-life

  • PK-CL/F [ Time Frame: Up to 13 days ] [ Designated as safety issue: No ]
    CL/F-Apparent total plasma clearance

  • PK-Vz/F [ Time Frame: Up to 13 days ] [ Designated as safety issue: No ]
    Vz/F: Apparent total volume of distribution


Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Up to 15 days ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events


Enrollment: 32
Study Start Date: September 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pomalidomide Drug: Pomalidomide
4 mg pomalidomide capsule administered orally once in the morning
Other Name: (CC-4047)
Experimental: Pomalidomide plus Ketoconazole Drug: Pomalidomide
4 mg pomalidomide capsule administered orally once in the morning
Other Name: (CC-4047)
Drug: Ketoconazole
200 mg Ketoconazole tablet administered orally twice a day on Days 1-7.
Experimental: Pomalidomide plus Ketoconazole plus Fluvoxamine Drug: Pomalidomide
4 mg pomalidomide capsule administered orally once in the morning
Other Name: (CC-4047)
Drug: Ketoconazole
200 mg Ketoconazole tablet administered orally twice a day on Days 1-7.
Drug: Fluvoxamine
50 mg Fluvoxamine tablet administered orally twice a day on Days 1-7.
Experimental: Pomalidomide plus Carbamazepine Drug: Pomalidomide
4 mg pomalidomide capsule administered orally once in the morning
Other Name: (CC-4047)
Drug: Carbamazepine

100 mg Carbamazepine tablet administered orally once in the evening on Day 1

100 mg Carbamazepine tablet administered orally twice daily on Days 2-3

200 mg Carbamazepine tablet administered orally twice daily on Days 4-11


Detailed Description:

This will be a single-center, open label non randomized, 2-part study with 3 periods in Part 1, and 2 periods in Part 2. Parts 1 and 2 will be conducted in parallel. The entire study will consist of a screening phase, two dosing parts, and a follow-up telephone call for safety. All Periods will be separated by a washout period of at least 3 days (no more than 5 days) from the last pomalidomide dose to the next drug dose.

Safety will be monitored throughout the study. Safety evaluations will include adverse event (AE) reporting, concomitant medications, PEs, vital sign measurements, 12-lead ECGs, and clinical laboratory safety tests.

Thirty-two healthy (16 per each Part), male adult subjects 18 to 55 years of age who meet all inclusion criteria and do not meet any of the exclusion criteria will be enrolled in the study. Subjects enrolled in Part 1 cannot participate in Part 2 and vice versa.

Study treatments (pomalidomide, ketoconazole, fluvoxamine and carbamazepine) should be administered with meals and subjects should be a served a standard meal (ie, breakfast or dinner) approximately 30 minutes prior to dosing. The meal should be consumed within 30 minutes from serving and dosing must occur 30 minutes (±5 minutes) after serving the meal. Subjects should be encouraged to consume the whole meal served prior to dosing. After each dosing, food and beverages (except water) will be withheld from all subjects until at least 4 hours post dose; thereafter, subjects will be served standard meals and snacks.

For determination of plasma concentrations of pomalidomide, ketoconazole, fluvoxamine and carbamazepine (and its active metabolite carbamazepine 10,11-epoxide) in each dosing regimen (Period), serial blood samples will be collected.

A safety follow-up will be conducted by telephone within 4 to 7 days from the last dose. In the event a subject discontinues from the study prematurely, an early termination visit will be performed within 4 days following the day of discontinuation.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • Must understand and voluntarily sign a written informed consent document (ICD) prior to any study-related procedures being performed.
  • 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.
  • Must be a male 18 to 55 years of age (inclusive) at the time of signing the ICD, with a body mass index (BMI = weight [kg]/(height [m2]) between 18 and 33 kg/m2 (inclusive) and weight between 60 and 100 kg (132 to 220 lbs; inclusive)

    1. For Part 1, subjects may be of any race.
    2. For Part 2, subjects must be non-Asian or non-Asian descent.
  • Must be healthy (at Screening and Day -1 of Period 1) as determined by the investigator on the basis of medical history, physical examination, clinical laboratory safety test results, vital signs, and 12 lead electrocardiograms (ECGs).

    1. Vital signs (systolic and diastolic blood pressure, pulse rate, and oral body temperature) will be assessed in the supine position after the subject has rested for at least 5 minutes.
    2. Subject must be afebrile (febrile is defined as ≥ 38.5ºC or 101.3 Fahrenheit).
    3. Systolic blood pressure in the range of 90 to 140 mmHg, diastolic blood pressure in the range of 60 to 90 mmHg, and pulse rate in the range of 45 to 100 bpm.
    4. Must have a normal or clinically acceptable 12-lead ECG, with a QTcF value ≤ 430 msec.
    5. Clinical laboratory safety tests must be within normal limits or clinically acceptable to the Principal investigator (PI)
  • Subjects (with or without vasectomy) must agree to use barrier contraception (ie, latex condom or any non-latex condom not made out of natural [animal] membrane [eg, polyurethane]) and one other method (eg, spermicide) when engaging in sexual activity with woman of child-bearing potential during study conduct, and for 90 days after the last dose of study medication.
  • Must agree to refrain from donating 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.
  • Similarly, must agree to refrain from donating sperm while participating in this study and for at least 90 days after the last dose of study drug.
  • Will be counseled about pregnancy precautions and risks of fetal exposure and agree to comply with the conditions described in the counseling document.

Exclusion Criteria:

  • History of any clinically significant and relevant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, known hypersensitivity to a member of the class of-IMIDs (immune-mediated inflammatory diseases), or other major disorders
  • Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he were to participate in the study.
  • Any condition that confounds the ability to interpret data from the study.
  • Used any prescribed systemic or topical medication within 30 days of the first dose administration, unless Sponsor agreement is obtained.
  • Used 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.
  • Has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion (ADME), eg, bariatric procedure.
  • Donated blood or plasma within 8 weeks before the first dose administration to a blood bank or blood donation center.
  • History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual within 2 years before dosing, or positive drug screening test reflecting consumption of illicit drugs.
  • History of alcohol abuse (as defined by the current version of the DSM) within 2 years before dosing, or positive alcohol screen.
  • Known to have, or tests positive for, active or chronic hepatitis B, hepatitis C, or HIV antibodies.
  • Exposed to an investigational drug (new chemical entity) within 60 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
  • Received vaccination (excluding seasonal flu vaccination) within 90 days of the study drug administration.
  • Smokes more than 10 cigarettes, or consumes the equivalent in tobacco, per day.
  • Subjects who are part of the staff personnel or family members of the investigational study staff.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01707407

Locations
United States, Wisconsin
Covance Research Unit, Inc
Madison, Wisconsin, United States, 53704
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Maria Palmisano, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01707407     History of Changes
Other Study ID Numbers: CC-4047-CP-008
Study First Received: October 12, 2012
Last Updated: December 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
CC-4047
Pomalidomide
Ketoconazole
Fluvoxamine
Carbamazepine
DDI
safety
tolerability
pharmacokinetic

Additional relevant MeSH terms:
Carbamazepine
Fluvoxamine
Ketoconazole
Thalidomide
Pomalidomide
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents

ClinicalTrials.gov processed this record on August 28, 2014