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Relapsed or Refractory Advanced CancerPhase 1NCT01071304

Effect of Ridaforolimus on the Pharmacokinetics of Midazolam (Study MK-8669-044)

A Phase 1 study testing Midazolam and Ridaforolimus in people with Relapsed or Refractory Advanced Cancer, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to compare the pharmacokinetic profile of midazolam given alone and midazolam given after multiple oral doses of 40 mg ridaforolimus. Part 1 of this study is designed for evaluating CYP3A4 activity following 5 days of dosing of ridaforolimus and is not designed with efficacy endpoints. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed or Refractory Advanced Cancer
What is being tested?
Midazolam and Ridaforolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
No sites listed yet
Study dates
Mar 2010to Feb 2012
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • participant is male or female
  • participant must have a histologically or cytologically-confirmed metastatic or locally
  • advanced solid tumor, lymphoma, or hematologic malignancy that has failed to
  • respond to standard therapy, progressed despite standard therapy, or for which
  • standard therapy does not exist. There is no limit on the number of prior treatment
  • regimens
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  • participant must have a performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • If participant is female she must be post menopausal (defined as free from menses for ≥1
  • year and follicle stimulating hormone (FSH) is in the postmenopausal range at screening), surgically sterilized
  • (hysterectomy, oophorectomy or tubal ligation) or, if of childbearing potential, must
  • be willing to use 2 approved methods of contraception (hormonal contraception,
  • intra-uterine device, diaphragm with spermicide, cervical cap with spermicide or
  • female condom with spermicide; spermicides alone are not an acceptable method of
  • contraception) from screening until 30 days following the last dose of study drug.
  • If participant is female and of childbearing potential, she must have a negative serum β-
  • human chorionic gonadotropin (hCG) pregnancy test at screening and within 24 hrs prior to dosing Part 1/Day -2
  • If participant is male and has female partner(s) of child-bearing potential, he must agree
  • to use a medically acceptable method of contraception during the study and for 30
  • days after the last dose of study drug. If the participant's partner is pregnant, the participant
  • must agree to use a condom. If the participant's partner is of child-bearing potential, he
  • must use a condom and his partner must additionally use one of the following
  • methods: hormonal contraception, intra-uterine device, diaphragm with spermicide,
  • cervical cap with spermicide or female condom with spermicide.
  • participant must have laboratory values within the parameters as outlined in the study protocol.
  • participant has a life expectancy of >3 months.
  • participant has voluntarily agreed to participate by giving written informed consent.
  • participant has enrolled in and complied with study procedures in Part 1 of the study.
  • participant is willing to comply with protocol requirements and procedures for Part 2 of
  • the study.

Who cannot join

  • participant has had chemotherapy, radiotherapy, or biological therapy within 4 weeks (6
  • weeks for nitrosoureas, mitomycin C, and monoclonal antibodies) prior to first dose
  • of study drug (Part 1/Day -2) or who has not recovered from adverse events due to
  • agents administered more than 4 weeks earlier.
  • participant is receiving any other concurrent anti-cancer therapy; participant may be receiving supportive therapy as defined in the study protocol
  • participant is receiving concurrent treatment with immunosuppressive agents, including
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  • corticosteroids at doses greater than those used for replacement therapy. Corticosteroids administered for replacement therapy at stable doses for ≥ 2 weeks are permitted.
  • participant has clinically significant abnormality on electrocardiogram (ECG) performed
  • at the prestudy (screening) visit and/or prior to administration of the initial dose of
  • study drug.
  • participant has significant or uncontrolled cardiovascular disease or a history of
  • congestive heart failure, unstable angina, or myocardial infarction. Controlled
  • hypertension < 150/100 mm Hg is allowed if participant is on a stable antihypertensive
  • regimen.
  • participant is currently participating or has participated in a study with an investigational
  • compound or device within 30 days prior to the first dose of study drug.
  • participant has a primary central nervous system tumor, an active brain metastases or
  • leptomeningeal carcinomatosis. participants with previously treated brain metastases that
  • are stable for > 3 months are eligible if a current brain magnetic resonance imaging (MRI) (within 28 days of the first dose of study drug) shows no edema or evidence of progression compared to a
  • prior MRI study (≥ 3 months ago).
  • participant has a history or current evidence of any condition, therapy, or lab abnormality
  • that might confound the results of the study, interfere with the participant's participation
  • for the full duration of the study, or is not in the best interest of the participant to
  • participate.
  • participant has a known psychiatric disorder that would interfere with giving informed
  • consent or cooperating with the requirements of the study.
  • participant is, at the time of signing informed consent, a regular user (including
  • use of any illicit drugs or had a recent history (within the last year) of
  • drug or alcohol abuse.
  • participant is pregnant or breastfeeding, or expecting to conceive within the projected
  • duration of the study.
  • participant is known to be Human Immunodeficiency Virus (HIV)-positive.
  • participant has a known history of Hepatitis B or C.
  • participant has newly diagnosed (within 3 months before the first dose of study drug) or
  • poorly controlled Type 1 or 2 diabetes.
  • participant requires treatment with medications that are inducers or inhibitors of
  • cytochrome P450 (CYP3A) prior to the first dose of study drug (Part 1/Day -2) and throughout the study until the
  • poststudy visit.
  • participant is currently taking or has a history of pronounced sedation upon taking
  • benzodiazepine or other sedative/soporific. The washout from prestudy use of these
  • medications should be at least five half-lives prior to the first dose of study drug in
  • Part 1 (Part 1/Day -2) and use during Part 1 is not permitted (use in Part 2 is
  • permitted).
  • participant has an active infection or has received intravenous antibiotics, antiviral, or
  • antifungal agents within 2 weeks prior to the first dose of the study drug.
  • participant will not refrain from the use of herbal remedies (such as St. John's Wort,
  • shark cartilage, etc.) from 2 weeks prior to the first dose (Part 1/Day -2) and
  • throughout the duration of the study.
  • participant is anticipated to require immunologic therapy, radiation therapy, surgery, or
  • chemotherapy during the study.
  • participant has received high-dose chemotherapy with stem cell rescue.
  • participant has had a blood transfusion within one week of study entry.
  • participant is unable to swallow capsules and/or has a documented surgical or anatomical
  • condition that will preclude the participant from swallowing and absorbing oral
  • medications on an ongoing basis.
  • participant has a known hypersensitivity to the components of the study drug or its
  • analogs or macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin).
  • participant has an allergy or hypersensitivity to midazolam or other benzodiazepines.
  • participant will not refrain from consumption of grapefruit or grapefruit juice for
  • approximately 2 weeks prior to first dosing (Part 1/Day -2) until the completion of the
  • study.
  • participant has not adequately recovered from any prior surgical procedure or has
  • undergone any major surgical procedure within 4 weeks prior to the first dose of
  • study drug. participants who have undergone minor procedures (e.g. placement of a
  • central venous access port) will be considered eligible it they have fully recovered.

About this study

Official title: A Study to Evaluate the Effect of Multiple Doses of Ridaforolimus (AP23573; MK-8669) on the Single Dose Pharmacokinetics of Midazolam.

The purpose of this study is to compare the pharmacokinetic profile of midazolam given alone and midazolam given after multiple oral doses of 40 mg ridaforolimus.

Part 1 of this study is designed for evaluating CYP3A4 activity following 5 days of dosing of ridaforolimus and is not designed with efficacy endpoints. Part 2 is a compassionate-use extension to give patients an opportunity to receive a clinically active dose of ridaforolimus. Part 2 dosing is open ended with limited data collection.

Being tested
Midazolam, Ridaforolimus
Keywords
Relapsed or refractory advanced cancer, metastatic cancer, locally advanced cancer
Medical subject headings
Recurrence, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MidazolamDrug

    A single oral dose of midazolam 2 mg (1 mL of 2 mg/mL syrup) was given on Day -2 and Day 5.

  • RidaforolimusDrug

    Ridaforolimus 40 mg (4 x 10 mg tablets) oral once daily on Days 1 through 5.

Study groups in NCT01071304
Study groupRoleWhat they receive
All ParticipantsExperimentalIn Part 1, all participants received a single oral dose of 2 mg midazolam on Day -2. On Days 1-5, all participants received daily single oral doses of ridaforolimus 40 mg ( 4 x 10 mg tablets). On Day 5, all participants received a single oral dose of 2 mg midazolam coadministered with the dose of ridaforolimus. Participants had the option to continue into Part 2 of this study.
Receives: Drug: Midazolam; Drug: Ridaforolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Concentration-time Curve (AUC [0-infinity]) of midazolam 2 mg administered alone versus when administered after multiple oral doses of ridaforolimus 40 mg.

    Measured: 8 days (Day -2 through Day 5, 24 hrs postdose)

  2. Maximum Concentration (Cmax) of midazolam 2 mg administered alone versus when administered after multiple oral doses of ridaforolimus 40 mg.

    Measured: 8 days (Day -2 through Day 5, 24 hrs postdose)

  3. Time to Cmax (Tmax) of a single oral dose of 2 mg midazolam administered alone versus when administered after multiple oral doses of ridaforolimus 40 mg.

    Measured: 8 days (Day -2 through Day 5, 24 hrs postdose)

  4. Apparent terminal half-life (t½) of a single oral dose of 2 mg midazolam administered alone versus when administered after multiple oral doses of ridaforolimus 40 mg.

    Measured: 8 days (Day -2 through Day 5, 24 hrs postdose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2010 (estimated)
  2. Study startMar 2010
  3. Primary completionSep 2010
  4. Study completionFeb 2012

Resources

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
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01071304
Sponsor's protocol ID
8669-044
Other IDs
2010_511
Status last verified
Apr 2015
First submitted
17 Feb 2010
Last updated
10 Apr 2015
Results posted
No
Data monitoring committee
No

Publications

  • Stroh M, Talaty J, Sandhu P, McCrea J, Patnaik A, Tolcher A, Palcza J, Orford K, Breidinger S, Narasimhan N, Panebianco D, Lush R, Papadopoulos KP, Wagner JA, Trucksis M, Agrawal N. Lack of meaningful effect of ridaforolimus on the pharmacokinetics of midazolam in cancer patients: model prediction and clinical confirmation. J Clin Pharmacol. 2014 Nov;54(11):1256-62. doi: 10.1002/jcph.331. Epub 2014 May 24.

    PubMed 24827931

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Midazolam and Ridaforolimus in people with Relapsed or Refractory Advanced Cancer, run by Merck Sharp & Dohme LLC.

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 29 inclusion and 65 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 10 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

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?

Area Under the Concentration-time Curve (AUC [0-infinity]) of midazolam 2 mg administered alone versus when administered after multiple oral doses of ridaforolimus 40 mg. (time frame: 8 days (Day -2 through Day 5, 24 hrs postdose)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01071304, which also lists 1 linked publication.

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 10 Apr 2015.

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