Food Effect and CYP1A2 Induction Study in Healthy Subjects

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02168205
• Other study ID #: CC-4047-CP-011
• Status: Completed
• Phase: Phase 1
• Start date: May 30, 2014
• Est. completion date: September 19, 2014

Study information

• Verified date: November 2018
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: September 19, 2014
• Est. primary completion date: September 19, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Pomalidomide
Capsules

Other:
• Caffeine
Capsules
• Tobacco
Cigarettes

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit	Daytona Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics - Cmax	Maximum observed concentration in plasma	Up to 8 days for Part 1; up to 10 days for Part 2
Primary	Pharmacokinetics - Tmax	Time to maximum observed concentration in plasma	Up to 8 days for Part 1; up to 10 days for Part 2
Primary	Pharmacokinetics - AUC	Area under the plasma concentration-time curve	Up to 8 days for Part 1; up to 10 days for Part 2
Primary	Pharmacokinetics - T1/2	Terminal half-life	Up to 8 days for Part 1; up to 10 days for Part 2
Primary	Pharmacokinetics - Vz/f	Apparent volume of distribution	Up to 8 days for Part 1; up to 10 days for Part 2
Primary	Pharmacokinetics - CL/F	Apparent total body clearance	Up to 8 days for Part 1; up to 10 days for Part 2
Secondary	Adverse events	Number of participants with adverse events	Approximately 1 month

External Links

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