Ignite Creation Date:
2025-12-24 @ 9:22 PM
Ignite Modification Date:
2026-01-01 @ 7:44 PM
Study NCT ID:
NCT01071304
Status:
COMPLETED
Last Update Posted:
2015-04-10
First Post:
2010-02-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Ridaforolimus on the Pharmacokinetics of Midazolam (Study MK-8669-044)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['United States']}, 'conditionBrowseModule': {'meshes': [{'id': 'D012008', 'term': 'Recurrence'}, {'id': 'D009362', 'term': 'Neoplasm Metastasis'}], 'ancestors': [{'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D009369', 'term': 'Neoplasms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008874', 'term': 'Midazolam'}, {'id': 'C515074', 'term': 'ridaforolimus'}], 'ancestors': [{'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 16}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-04', 'completionDateStruct': {'date': '2012-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-04-09', 'studyFirstSubmitDate': '2010-02-17', 'studyFirstSubmitQcDate': '2010-02-18', 'lastUpdatePostDateStruct': {'date': '2015-04-10', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2010-02-19', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2010-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'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.', 'timeFrame': '8 days (Day -2 through Day 5, 24 hrs postdose)'}, {'measure': 'Maximum Concentration (Cmax) of midazolam 2 mg administered alone versus when administered after multiple oral doses of ridaforolimus 40 mg.', 'timeFrame': '8 days (Day -2 through Day 5, 24 hrs postdose)'}, {'measure': '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.', 'timeFrame': '8 days (Day -2 through Day 5, 24 hrs postdose)'}, {'measure': '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.', 'timeFrame': '8 days (Day -2 through Day 5, 24 hrs postdose)'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Relapsed or refractory advanced cancer, metastatic cancer, locally advanced cancer'], 'conditions': ['Relapsed or Refractory Advanced Cancer']}, 'referencesModule': {'references': [{'pmid': '24827931', 'type': 'RESULT', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nPart 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* participant is male or female\n* participant must have a histologically or cytologically-confirmed metastatic or locally\n\nadvanced solid tumor, lymphoma, or hematologic malignancy that has failed to\n\nrespond to standard therapy, progressed despite standard therapy, or for which\n\nstandard therapy does not exist. There is no limit on the number of prior treatment\n\nregimens\n\n* participant must have a performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale\n* If participant is female she must be post menopausal (defined as free from menses for ≥1\n\nyear and follicle stimulating hormone (FSH) is in the postmenopausal range at screening), surgically sterilized\n\n(hysterectomy, oophorectomy or tubal ligation) or, if of childbearing potential, must\n\nbe willing to use 2 approved methods of contraception (hormonal contraception,\n\nintra-uterine device, diaphragm with spermicide, cervical cap with spermicide or\n\nfemale condom with spermicide; spermicides alone are not an acceptable method of\n\ncontraception) from screening until 30 days following the last dose of study drug.\n\n* If participant is female and of childbearing potential, she must have a negative serum β-\n\nhuman chorionic gonadotropin (hCG) pregnancy test at screening and within 24 hrs prior to dosing Part 1/Day -2\n\n* If participant is male and has female partner(s) of child-bearing potential, he must agree\n\nto use a medically acceptable method of contraception during the study and for 30\n\ndays after the last dose of study drug. If the participant's partner is pregnant, the participant\n\nmust agree to use a condom. If the participant's partner is of child-bearing potential, he\n\nmust use a condom and his partner must additionally use one of the following\n\nmethods: hormonal contraception, intra-uterine device, diaphragm with spermicide,\n\ncervical cap with spermicide or female condom with spermicide.\n\n\\- participant must have laboratory values within the parameters as outlined in the study protocol.\n\n* participant has a life expectancy of \\>3 months.\n* participant has voluntarily agreed to participate by giving written informed consent.\n\nInclusion Criteria for Part 2 of the study:\n\n* participant has enrolled in and complied with study procedures in Part 1 of the study.\n* participant is willing to comply with protocol requirements and procedures for Part 2 of\n\nthe study.\n\nExclusion Criteria:\n\n\\- participant has had chemotherapy, radiotherapy, or biological therapy within 4 weeks (6\n\nweeks for nitrosoureas, mitomycin C, and monoclonal antibodies) prior to first dose\n\nof study drug (Part 1/Day -2) or who has not recovered from adverse events due to\n\nagents administered more than 4 weeks earlier.\n\n* participant is receiving any other concurrent anti-cancer therapy; participant may be receiving supportive therapy as defined in the study protocol\n* participant is receiving concurrent treatment with immunosuppressive agents, including\n\ncorticosteroids at doses greater than those used for replacement therapy. Corticosteroids administered for replacement therapy at stable doses for ≥ 2 weeks are permitted.\n\n\\- participant has clinically significant abnormality on electrocardiogram (ECG) performed\n\nat the prestudy (screening) visit and/or prior to administration of the initial dose of\n\nstudy drug.\n\n\\- participant has significant or uncontrolled cardiovascular disease or a history of\n\ncongestive heart failure, unstable angina, or myocardial infarction. Controlled\n\nhypertension \\< 150/100 mm Hg is allowed if participant is on a stable antihypertensive\n\nregimen.\n\n\\- participant is currently participating or has participated in a study with an investigational\n\ncompound or device within 30 days prior to the first dose of study drug.\n\n\\- participant has a primary central nervous system tumor, an active brain metastases or\n\nleptomeningeal carcinomatosis. participants with previously treated brain metastases that\n\nare 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\n\nprior MRI study (≥ 3 months ago).\n\n\\- participant has a history or current evidence of any condition, therapy, or lab abnormality\n\nthat might confound the results of the study, interfere with the participant's participation\n\nfor the full duration of the study, or is not in the best interest of the participant to\n\nparticipate.\n\n\\- participant has a known psychiatric disorder that would interfere with giving informed\n\nconsent or cooperating with the requirements of the study.\n\n\\- participant is, at the time of signing informed consent, a regular user (including\n\nuse of any illicit drugs or had a recent history (within the last year) of\n\ndrug or alcohol abuse.\n\n\\- participant is pregnant or breastfeeding, or expecting to conceive within the projected\n\nduration of the study.\n\n* participant is known to be Human Immunodeficiency Virus (HIV)-positive.\n* participant has a known history of Hepatitis B or C.\n* participant has newly diagnosed (within 3 months before the first dose of study drug) or\n\npoorly controlled Type 1 or 2 diabetes.\n\n\\- participant requires treatment with medications that are inducers or inhibitors of\n\ncytochrome P450 (CYP3A) prior to the first dose of study drug (Part 1/Day -2) and throughout the study until the\n\npoststudy visit.\n\n\\- participant is currently taking or has a history of pronounced sedation upon taking\n\nbenzodiazepine or other sedative/soporific. The washout from prestudy use of these\n\nmedications should be at least five half-lives prior to the first dose of study drug in\n\nPart 1 (Part 1/Day -2) and use during Part 1 is not permitted (use in Part 2 is\n\npermitted).\n\n\\- participant has an active infection or has received intravenous antibiotics, antiviral, or\n\nantifungal agents within 2 weeks prior to the first dose of the study drug.\n\n\\- participant will not refrain from the use of herbal remedies (such as St. John's Wort,\n\nshark cartilage, etc.) from 2 weeks prior to the first dose (Part 1/Day -2) and\n\nthroughout the duration of the study.\n\n\\- participant is anticipated to require immunologic therapy, radiation therapy, surgery, or\n\nchemotherapy during the study.\n\n* participant has received high-dose chemotherapy with stem cell rescue.\n* participant has had a blood transfusion within one week of study entry.\n* participant is unable to swallow capsules and/or has a documented surgical or anatomical\n\ncondition that will preclude the participant from swallowing and absorbing oral\n\nmedications on an ongoing basis.\n\n\\- participant has a known hypersensitivity to the components of the study drug or its\n\nanalogs or macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin).\n\n* participant has an allergy or hypersensitivity to midazolam or other benzodiazepines.\n* participant will not refrain from consumption of grapefruit or grapefruit juice for\n\napproximately 2 weeks prior to first dosing (Part 1/Day -2) until the completion of the\n\nstudy.\n\n\\- participant has not adequately recovered from any prior surgical procedure or has\n\nundergone any major surgical procedure within 4 weeks prior to the first dose of\n\nstudy drug. participants who have undergone minor procedures (e.g. placement of a\n\ncentral venous access port) will be considered eligible it they have fully recovered."}, 'identificationModule': {'nctId': 'NCT01071304', 'briefTitle': 'Effect of Ridaforolimus on the Pharmacokinetics of Midazolam (Study MK-8669-044)', 'organization': {'class': 'INDUSTRY', 'fullName': 'Merck Sharp & Dohme LLC'}, 'officialTitle': 'A Study to Evaluate the Effect of Multiple Doses of Ridaforolimus (AP23573; MK-8669) on the Single Dose Pharmacokinetics of Midazolam.', 'orgStudyIdInfo': {'id': '8669-044'}, 'secondaryIdInfos': [{'id': '2010_511'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'All Participants', 'description': 'In 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.', 'interventionNames': ['Drug: Midazolam', 'Drug: Ridaforolimus']}], 'interventions': [{'name': 'Midazolam', 'type': 'DRUG', 'description': 'A single oral dose of midazolam 2 mg (1 mL of 2 mg/mL syrup) was given on Day -2 and Day 5.', 'armGroupLabels': ['All Participants']}, {'name': 'Ridaforolimus', 'type': 'DRUG', 'description': 'Ridaforolimus 40 mg (4 x 10 mg tablets) oral once daily on Days 1 through 5.', 'armGroupLabels': ['All Participants']}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Merck Sharp & Dohme LLC', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}