Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Males

NCT01712828 | Completed Phase 1

• 1 other identifier: CC-5013-CP-011
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

To find out if the blood level of lenalidomide can be changed when a drug that prevents p-glycoprotein (a protein naturally present in the body that helps carry substances across cell membranes that is found in many parts of the body like the intestines, liver, and kidneys) from working (called a P-gp inhibitor) when taken together with lenalidomide. The study is also trying to find out if blood level of temsirolimus can be changed when a subject takes lenalidomide together with temsirolimus.

Conditions

Healthy

Keywords

Lenalidomide,; Revlimid,; pharmacokinetics,; healthy male subjects

Outcome Measures

Primary Outcomes (10)

• Lenalidomide PK-AUC (0-24)

  Area under the plasma concentration-time curve from time zero to 24 hours post dose

  Up to 21 days

• Lenalidomide PK-(Cmax)

  Maximum observed plasma concentration

  Up to 21 days (including washout phase)

• Lenalidomide PK-(Tmax)

  Time to maximum observed plasma concentration

  Up to 21 days

• Lenalidomide PK-AUC(0-t)

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

  Up to 21 days

• Lenalidomide PK-AUC(0-∞)

  Area under the plasma concentration-time curve from time zero extrapolated to infinity

  Up to 21 days

• Lenalidomide PK-(T1/2)

  Estimate of the terminal elimination half-life in plasma

  Up to 21 days

• Temsirolimus and Sirolimus PK-AUC (0-24)

  Area under the plasma concentration-time curve from time zero to 24 hours post dose

  Up to 38 days

• Temsirolimus and Sirolimus PK-(Cmax)

  Maximum observed plasma concentration

  Up to 38 days

• Temsirolimus and Sirolimus PK-(Tmax)

  Time to maximum observed plasma concentration

  Up to 38 days

• Temsirolimus and Sirolimus PK-(AUC 0-t)

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

  Up to 38 days

Secondary Outcomes (1)

• Number of participants with adverse events

  Up to 6 weeks

Study Arms (2)

Lenalidomide plus Quinidine

EXPERIMENTAL

Drug: Lenalidomide; Drug: Quinidine

Lenalidomide plusTemsirolimus and Diphenhydramine

EXPERIMENTAL

Drug: Lenalidomide; Drug: Temsirolimus; Drug: Diphenhydramine

Interventions

Lenalidomide DRUG

25 mg Lenalidomide capsule will be administered orally once in the first period, and once with Quinidine in the second period

Lenalidomide plus Quinidine; Lenalidomide plusTemsirolimus and Diphenhydramine

Quinidine DRUG

300 mg of Quinidine will be administered orally every 12 hours for 1 day followed by 600 mg of Quinidine administered orally every 12 hours for the next 4 consecutive days

Lenalidomide plus Quinidine

Temsirolimus DRUG

25 mg/mL injection of Temsirolimus will be given directly into the vein over 30 minutes once in the second period and once with Lenalidomide in the third period.

Lenalidomide plusTemsirolimus and Diphenhydramine

Diphenhydramine DRUG

Just before Temsirolimus is given, 25 mg of Diphenhydramine (Benadryl) will be given directly into the vein to decrease chances of an allergic reaction to Temsirolimus.

Also known as: Benadryl

Lenalidomide plusTemsirolimus and Diphenhydramine

Eligibility Criteria

• Age: 18 Years - 65 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 form 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.
• Healthy male volunteer of any race between 18 to 65 years of age (inclusive), and in good health as determined by a physical exam.
• Agree to use barrier contraception (i.e., condoms not made of natural (animal) membrane \[e.g., latex or polyurethane condoms are acceptable\]) when engaging in sexual activity with a female of child-bearing potential while on study drug, and for at least 90 days after the last dose of study drug.
• Must have a body mass index between 18 and 33 kg/m2 (inclusive).
• Clinical laboratory tests must be within normal limits or acceptable to the principal investigator.
• Must have confirmation of normal renal function (defined as an estimate glomerular filtration rate \>90 mL/min).
• Must be afebrile, with supine 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 electrocardiogram, with a QTcF (Fridericia's correction formula) value ≤ 430 msec.
• Must refrain from sperm donations for the entire duration of the study, and for at least 90 days after the last dose of study drug.

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 immunomodulatory drugs (IMiDs®), temosirolimus, sirolimus, polysorbate 80, diphenhydramine, or to any other component (or excipients) of Torisel®, 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.
• Used any prescribed, or non-prescribed, systemic or topical medication that is a CYP3A inhibitor or inducer within 30 days of first dose administration. (refer to (http://medicine.iupui.edu/clinpharm/ddis/p450\_Table\_Oct\_11\_2009.pdf)
• Has any surgical or medical conditions (excluding appendectomy) possibly affecting drug absorption, distribution, metabolism and excretion, e.g., 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 Diagnostic and Statistical Manual) 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 (HCVAb), 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).
• For Part 2 only: has total bilirubin ≥ 1.5x upper limit of normal

Sponsors & Collaborators

• Celgene: lead
• Covance: collaborator

Study Sites (1)

Covance Clinical Research Unit Dallas

Dallas, Texas, 75247, United States

Location

Related Links

• Related Info

MeSH Terms

Interventions

Lenalidomide; Quinidine; temsirolimus; Diphenhydramine

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cinchona Alkaloids; Alkaloids; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2012
• First Posted: October 24, 2012
• Study Start: October 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: November 8, 2019

Record last verified: 2019-11

Locations

US (1)