A Study to Evaluate the Effect of Multiple Doses of Ridaforolimus (AP23573; MK-8669) on the Single Dose Pharmacokinetics of Midazolam.
- 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
- 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
- participant has a life expectancy of >3 months.
- participant has voluntarily agreed to participate by giving written informed consent.
Inclusion Criteria for Part 2 of the study:
- participant has enrolled in and complied with study procedures in Part 1 of the
- participant is willing to comply with protocol requirements and procedures for Part 2
of the study.
- 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 corticosteroids at doses greater than those used for replacement therapy.
Corticosteroids administered for replacement therapy at stable doses for ≥ 2 weeks
- 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
- 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
- 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
- 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
- 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
- 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
- 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.