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

November 6, 2019 updated by: Celgene

A Phase 1, Open-Label, Two-Part, Fixed-Sequence Crossover Study to Evaluate the Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Male Subjects

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This will be a single-center, open label, 2-part study. Part 1 will be a two-period, fixed-sequence crossover study with lenalidomide alone in Period 1, followed by lenalidomide in combination with quinidine in Period 2. Part 2 will be a fixed-sequence, three-period, crossover study with lenalidomide alone in Period 1, temsirolimus (via direct intravenous infusion) in Period 2, and lenalidomide in combination with temsirolimus (via direct intravenous infusion) in Period 3. Diphenhydramine (given via intravenous injection) will be administered shortly before temsirolimus in order to decrease the chances of an allergic reaction to temsirolimus. Part 1 and Part 2 will be conducted at the same time. Subjects can only participate in either Part 1 or Part 2.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
31

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75247
        • Covance Clinical Research Unit Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 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.

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lenalidomide plus Quinidine
Drug: Lenalidomide
25 mg Lenalidomide capsule will be administered orally once in the first period, and once with Quinidine in the second period
Drug: Quinidine
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
Experimental: Lenalidomide plusTemsirolimus and Diphenhydramine
Drug: Lenalidomide
25 mg Lenalidomide capsule will be administered orally once in the first period, and once with Quinidine in the second period
Drug: Temsirolimus
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.
Drug: Diphenhydramine
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.
Other Names:
  • Benadryl

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Lenalidomide PK-AUC (0-24)
Time Frame: Up to 21 days
Area under the plasma concentration-time curve from time zero to 24 hours post dose
Up to 21 days
Lenalidomide PK-(Cmax)
Time Frame: Up to 21 days (including washout phase)
Maximum observed plasma concentration
Up to 21 days (including washout phase)
Lenalidomide PK-(Tmax)
Time Frame: Up to 21 days
Time to maximum observed plasma concentration
Up to 21 days
Lenalidomide PK-AUC(0-t)
Time Frame: Up to 21 days
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-∞)
Time Frame: Up to 21 days
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Up to 21 days
Lenalidomide PK-(T1/2)
Time Frame: Up to 21 days
Estimate of the terminal elimination half-life in plasma
Up to 21 days
Temsirolimus and Sirolimus PK-AUC (0-24)
Time Frame: Up to 38 days
Area under the plasma concentration-time curve from time zero to 24 hours post dose
Up to 38 days
Temsirolimus and Sirolimus PK-(Cmax)
Time Frame: Up to 38 days
Maximum observed plasma concentration
Up to 38 days
Temsirolimus and Sirolimus PK-(Tmax)
Time Frame: Up to 38 days
Time to maximum observed plasma concentration
Up to 38 days
Temsirolimus and Sirolimus PK-(AUC 0-t)
Time Frame: Up to 38 days
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: Up to 6 weeks
Safety monitoring will be done by regular adverse event assessment, concomitant medication, clinical laboratory tests, physical exams, ECGs, and vital signs.
Up to 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Celgene

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Covance

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 22, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 22, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 24, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 8, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CC-5013-CP-011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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