Study to Evaluate Pharmacokinetics of Pomalidomide in Hepatically Impaired Males

NCT01835561 | Completed Phase 1

• 1 other identifier: CC-4047-CP-009
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This study is for research purposes only and will not treat any disease or condition you may have. The study is an open label and single dose study; open label means that you, the study doctor and study staff will know which study drug you are taking. The purpose of this research study is to compare drug levels in the body of people with liver disease to drug levels in healthy people with a normal liver. In addition, the safety of the study drug will be studied. Information about any side effects (discomfort or decline in health) that may happen will be collected. The study drug will be given by mouth to subjects with liver disease and to healthy subjects. In the body, drugs are normally removed by the liver with a smaller amount being removed by the kidneys. When the liver is not working as well as it should, the body may not be able to remove drugs from the body quickly. The information from this study will be used to decide if the drug is safe in subjects with liver disease or if a lower dose of the study drug would be safer.

Conditions

Clinical Pharmacology, Healthy Volunteer Study

Keywords

Hepatic, Liver disease; Pharmacokinetic; Healthy

Outcome Measures

Primary Outcomes (7)

• C max

  Observed maximum concentration; PK parameter for plasma pomalidomide

  At predose (0-hour) and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, 40 and 48 hours post dose

• T max

  Time to Cmax

  At predose (0-hour) and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, 40 and 48 hours post dose

• Area Under the Curve Time Zero to time(AUC0-t)

  Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point

  At predose (0-hour) and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, 40 and 48 hours post dose

• Area Under the Curve (AUCinf) ; from time 0 to infinity

  Area under the plasma concentration-time curve from time zero extrapolated to infinity; PK parameter for plasma pomalidomide

  At predose (0-hour) and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, 40 and 48 hours post dose

• t ½: Terminal Half Life

  Estimate of the terminal elimination half-life in plasma 5. delay between time of administration and absorption

  At predose (0-hour) and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, 40 and 48 hours post dose

• CL/F: apparent clearance

  Apparent total plasma or serum clearance of drug after oral administration

  At predose (0-hour) and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, 40 and 48 hours post dose

• Vz/F: apparent volume of distribution

  Apparent volume of distribution during terminal phase after oral / extravascular administration

  At predose (0-hour) and at 0.25, 1, 2, 2.5, 4, 6, 8, 12, 24, 30, 40 and 48 hours post dose

Secondary Outcomes (1)

• Number of participants with adverse events (AEs).

  1 month (from screening visit to end of study follow-up telephone call).

Study Arms (2)

Part 1: Severe liver disease and healthy volunteer match

EXPERIMENTAL

Subjects with severe liver disease (Group 2) and healthy volunteer subjects (Group 1) matched to the subjects with liver disease

Drug: Pomalidomide

Part 2: Mild and moderate Liver disease

EXPERIMENTAL

Subjects with moderate (Group 3) and/or mild (Group 4) liver disease

Drug: Pomalidomide

Interventions

Pomalidomide DRUG

Single oral dose of 4-mg capsule

Also known as: POMALYST®

Part 1: Severe liver disease and healthy volunteer match

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 male subjects of any race between 18 to 70 years of age, inclusive, with a body mass index between 18 and 37 kg/m2 (inclusive).
• Subjects must be in good health (at screening and baseline \[Day -1\]) as determined by the investigator on the basis of medical history, physical examination, clinical laboratory safety test results, vital signs, and 12 lead ECG.
• Clinical laboratory safety tests must be within normal limits or acceptable to the investigator (at screening and baseline \[Day -1\]), and in particular:
• a. Creatinine less than or equal to 1.5x upper limit of normal (ULN)
• Must be afebrile, with supine (after the subject has rested for at least 5 minutes) systolic blood pressure: 90 to 140 mmHg, supine diastolic blood pressure: 60 to 90 mmHg, and pulse rate: 40 to 110 bpm.
• Must have a normal or clinically acceptable 12-lead ECG. Male subjects must have a QTcF value ≤ 430 msec.
• Subjects (with or without vasectomy) must practice true abstinence\* or agree to use double 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 28 days after the last dose of study medication.
• \* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
• 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.
• Subjects who have not performed strenuous physical activity for at least 72 hours prior to the dose of study drug and agree to not engage in strenuous physical activity throughout the study and until study completion (follow-up safety telephone call).
• Will be counseled about pregnancy precautions and risks of fetal exposure and agree to comply with the conditions described in the counseling document.
• Must understand and voluntarily sign a written informed consent form (ICF) 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.

You may not qualify if:

• 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, or other major disorders.
• 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.
• 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), including but not limited to: bariatric procedure, irritable bowel syndrome (IBS), peptic ulcer(s),cholecystectomy, and chronic liver disease.
• 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 (DSM) 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 serum hepatitis or known to be a carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C antibody, or have a positive result to the test for HIV antibodies at Screening.
• 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).
• 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.
• Subjects who, for any reason, are deemed by the investigator to be inappropriate for this study, including subjects who are unable to communicate or to cooperate with the investigator or the clinical staff.
• Any serious medical condition (excluding hepatic impairment and related complications), clinically significant laboratory abnormality not related to hepatic impairment and related complications, or psychiatric illness that would prevent the subject from signing the ICD and participating in the study.
• Any unstable clinically significant illness other than moderate or severe hepatic impairment within 3 months prior to the subject signing the ICD.

Sponsors & Collaborators

• Celgene: lead

Study Sites (2)

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

MeSH Terms

Conditions

Liver Diseases

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• Edward O'Mara, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 19, 2013
• Study Start: March 1, 2013
• Primary Completion: August 16, 2014
• Study Completion: August 21, 2014
• Last Updated: November 12, 2019

Record last verified: 2019-11

Locations

US (2)