HealthyPhase 1NCT01712828
Effect of P-glycoprotein Inhibition on Lenalidomide Pharmacokinetics in Healthy Males
A Phase 1 study testing Lenalidomide, Quinidine and Temsirolimus in people with Healthy, run by Celgene at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Lenalidomide, Quinidine and Temsirolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2012to 1 Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Covance Clinical Research Unit Dallas
Dallas, Texas, 75247
About this study
Official title: 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.
Read the 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.
- Conditions
- Healthy
- Being tested
- Lenalidomide, Quinidine, Temsirolimus, Diphenhydramine
- Keywords
- Lenalidomide,, Revlimid,, pharmacokinetics,, healthy male subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
25 mg Lenalidomide capsule will be administered orally once in the first period, and once with Quinidine in the second period
QuinidineDrug
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
TemsirolimusDrug
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.
DiphenhydramineDrug
Also called Benadryl
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.
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide plus Quinidine | Experimental | Not described Receives: Drug: Lenalidomide; Drug: Quinidine |
| Lenalidomide plusTemsirolimus and Diphenhydramine | Experimental | Not described Receives: Drug: Lenalidomide; Drug: Temsirolimus; Drug: Diphenhydramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lenalidomide PK-AUC (0-24)
Area under the plasma concentration-time curve from time zero to 24 hours post dose
Measured: Up to 21 days
Lenalidomide PK-(Cmax)
Maximum observed plasma concentration
Measured: Up to 21 days (including washout phase)
Lenalidomide PK-(Tmax)
Time to maximum observed plasma concentration
Measured: 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
Measured: Up to 21 days
Lenalidomide PK-AUC(0-∞)
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Measured: Up to 21 days
Lenalidomide PK-(T1/2)
Estimate of the terminal elimination half-life in plasma
Measured: 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
Measured: Up to 38 days
Temsirolimus and Sirolimus PK-(Cmax)
Maximum observed plasma concentration
Measured: Up to 38 days
Temsirolimus and Sirolimus PK-(Tmax)
Time to maximum observed plasma concentration
Measured: 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
Measured: Up to 38 days
Secondary outcomes (1)
Number of participants with adverse events
Safety monitoring will be done by regular adverse event assessment, concomitant medication, clinical laboratory tests, physical exams, ECGs, and vital signs.
Measured: Up to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2012 (estimated)
- Study start1 Oct 2012
- Primary completion1 Jan 2013
- Study completion1 Jan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Covance
- Responsible party
- Sponsor
- Investigators
- Edward O'Mara, MD, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01712828
- Sponsor's protocol ID
- CC-5013-CP-011
- Status last verified
- Nov 2019
- First submitted
- 22 Oct 2012
- Last updated
- 8 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01712828
- Acronym / sponsor ID
- CC-5013-CP-011
- Conditions
- Healthy
- Keywords
- Lenalidomide,, Revlimid,, pharmacokinetics,, healthy male subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Collaborators
- Covance
- Study start
- 1 Oct 2012 (actual)
- Primary completion
- 1 Jan 2013 (actual)
- Study completion
- 1 Jan 2013 (actual)
- First posted
- 24 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide plus Quinidine | Experimental | Drug: Lenalidomide, Drug: Quinidine |
| Lenalidomide plusTemsirolimus and Diphenhydramine | Experimental | Drug: Lenalidomide, Drug: Temsirolimus, Drug: Diphenhydramine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lenalidomide25 mg Lenalidomide capsule will be administered orally once in the first period, and once with Quinidine in the second period | Drug | Lenalidomide plus Quinidine, Lenalidomide plusTemsirolimus and Diphenhydramine |
| Quinidine300 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 | Drug | Lenalidomide plus Quinidine |
| Temsirolimus25 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 | Lenalidomide plusTemsirolimus and Diphenhydramine |
| DiphenhydramineAlso: BenadrylJust 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. | Drug | Lenalidomide plusTemsirolimus and Diphenhydramine |
Primary outcome
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
Lenalidomide PK-(Cmax)
Time frame: Up to 21 days (including washout phase)
Maximum observed plasma concentration
Lenalidomide PK-(Tmax)
Time frame: Up to 21 days
Time to maximum observed plasma concentration
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
Lenalidomide PK-AUC(0-∞)
Time frame: Up to 21 days
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Lenalidomide PK-(T1/2)
Time frame: Up to 21 days
Estimate of the terminal elimination half-life in plasma
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
Temsirolimus and Sirolimus PK-(Cmax)
Time frame: Up to 38 days
Maximum observed plasma concentration
Temsirolimus and Sirolimus PK-(Tmax)
Time frame: Up to 38 days
Time to maximum observed plasma concentration
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
1 secondary outcome
Number of participants with adverse events
Time frame: Up to 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2019.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward O'Mara, MD study director
Celgene Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenalidomide, Quinidine and Temsirolimus in people with Healthy, run by Celgene at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lenalidomide PK-AUC (0-24) (time frame: Up to 21 days). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2019.