Clinical trial NCT02168205: Food Effect and CYP1A2 Induction Study in Healthy Subjects
Official title: Hase I Open-Label Two-Part Study To Evaluate The Effect Of Food and Of CYP1A2 Induction On Pomalidomide (CC-4047) Pharmacokinetics in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Healthy volunteer
Pharmacokinetics
Pomalyst
Pomalidomide
Food effect
smoker
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-06-20
Enrollment: 55
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This study will evaluate the effect of food and smoking on healthy older subjects taking pomalidomide.

Detailed description: This study will be conducted in two parts. Parts 1 and 2 may be conducted in parallel and subjects are only allowed to participate in one part.

In Part 1, subjects will be randomly assigned to receive a single oral dose of 4 mg pomalidomide on Day 1 under fed (standard high fat breakfast) or fasted conditions. After a washout period of at least 3 and no more than 7 days, subjects will receive a single oral dose of 4 mg pomalidomide under the opposite condition to what they received in the first period.

In Part 2, healthy male smoker subjects must smoke approximately 20 cigarettes per day for a total of 10 days. Non-smokers will neither smoke nor be in the presence of smokers. All subjects will receive orally a 200-mg caffeine capsule on Day 6, and on Day 8, subjects will receive a single oral dose of 4 mg pomalidomide.

For both Parts 1 and 2, serial blood samples will be collected for determination of plasma pomalidomide concentrations.

Eligibility criteria: Inclusion Criteria:

* Part 1: 1.Must understand and voluntarily sign a written Informed Consent 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.Must be male or postmenopausal\* women of any race between ≥61 to ≤85 years of age (inclusive) at the time of signing the Informed Consent, and in good health as determined by a physical exam, clinical laboratory safety test results, vital signs, and 12 lead Electrocardiogram.

  \* =Naturally postmenopausal for at least 24 consecutive months (ie, who has not had menses at any time in the preceding 24 consecutive months) 4.Subjects must be a non smoker. 5.Clinical laboratory tests must be within normal limits or acceptable to the Principal Investigator (PI).

  6.Must have a normal or clinically acceptable 12-lead Electrocardiogram. 7.Must be afebrile (febrile is defined as ≥ 38.0ºC or 100.4 Fahrenheit), with supine systolic blood pressure (BP): 90 to 150 mmHg, supine diastolic blood pressure: 60 to 95 mmHg, and pulse rate: 40 to 110 bpm and controlled on medications if they are indicated (especially for blood pressure).
  1. If a subject has a diagnosis of hypertension, the range for BP and pulse rate will be the one that is considered well controlled on medication.

     8.Must practice true abstinence\* or agree to use a condom during sexual contact with a pregnant female or a female that can get pregnant while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.

     \* = True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Period abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception 9.Must agree to refrain from donating sperm or semen while participating in this study and for at least 28 days following the last dose of study drug.

     10.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 following the last dose of study drug.

     11.Must agree to comply with the conditions described in the counseling document (part of the pomalidomide Pregnancy Prevention Risk Management Plan.

     Part 2
     1. Must understand and voluntarily sign a written informed consent 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. Must be male of any race between 40 to 80 years of age (inclusive) at the time of signing the Informed Consent, and in good health as determined by a physical exam, clinical laboratory safety test results, vital signs, and 12 lead electrocardiogram.
     4. Cohort A subjects (smokers) must have a history of smoking for \>5 years and currently smoke ≥1 pack (20-25) cigarettes per day; and urine cotinine level at screening and baseline (Day -1) indicate subject is heavy smoker.
     5. Cohort B subjects (non-smokers) must have not smoked for \>5 years (Cohort B).
     6. Clinical laboratory tests must be within normal limits or acceptable to the Principal Investigator.
     7. Must have a normal or clinically acceptable 12-lead Electrocardiogram, with a QTcF value ≤ 450 msec.
     8. Must be afebrile (febrile is defined as ≥ 38.0ºC or 100.4 Fahrenheit), with supine systolic blood pressure (BP): 90 to 150 mmHg, supine diastolic blood pressure: 60 to 95 mmHg, and pulse rate: 40 to 110 bpm and controlled on medications if they are indicated (especially for blood pressure).
     9. Must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female that can get pregnant while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.
     10. Must agree to refrain from donating sperm or semen while participating in this study and for at least 28 days following the last dose of study drug.
     11. 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 following the last dose of study drug.
     12. Must agree to comply with the conditions described in the counseling document (part of the pomalidomide Pregnancy Prevention Risk Management Plan.

     Exclusion Criteria:
* Both Parts:

  1. 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 drugs that can modulate the immune system, or other major disorders.

     1. Subjects with well-controlled hypertension, hyperlipidemia, gout, asthma/chronic obstructive pulmonary disease, hypothyroidism and other common age-related disorders, requiring treatment and being well-controlled on concomitant prescription medication(s) will be eligible for inclusion in the study.
     2. Subjects with diabetes, significant gastrointestinal diseases or hematologic disorders should not be included in the study.
  2. Any condition, including the presence of laboratory abnormalities, 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. Used any prescribed systemic or topical medication within 30 days of the first dose administration, unless these medications are chronically administered and Sponsor agreement is obtained.
  4. Used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days of the first dose administration, unless these medications are chronically administered and Sponsor agreement is obtained.
  5. Has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism and excretion, e.g., bariatric procedure.
  6. Donated 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 within 2 years before dosing, 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 dosing, or positive alcohol screen.
  9. Known to have serum hepatitis or known to be a carrier of the hepatitis B surface antigen, or hepatitis C antibody, or have a positive result to the test for Human Immunodeficiency Virus antibodies at Screening.
  10. Exposed 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).
  11. Received vaccination (excluding seasonal flu vaccination) within 90 days of the study drug administration.
  12. Subjects who are part of the staff personnel or family members of the investigational study staff.

Primary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: Up to 8 days for Part 1; up to 10 days for Part 2
measure: Pharmacokinetics - Tmax
timeFrame: Up to 8 days for Part 1; up to 10 days for Part 2
measure: Pharmacokinetics - AUC
timeFrame: Up to 8 days for Part 1; up to 10 days for Part 2
measure: Pharmacokinetics - T1/2
timeFrame: Up to 8 days for Part 1; up to 10 days for Part 2
measure: Pharmacokinetics - Vz/f
timeFrame: Up to 8 days for Part 1; up to 10 days for Part 2
measure: Pharmacokinetics - CL/F
timeFrame: Up to 8 days for Part 1; up to 10 days for Part 2
Secondary outcomes:
measure: Adverse events
timeFrame: Approximately 1 month
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Clinical Research Unit
state: Florida
Study officials:
affiliation: Celgene
name: Edward O'Mara, MD
role: STUDY_DIRECTOR
References: