A Study to Evaluate the Effect of Multiple Doses of Ridaforolimus (AP23573; MK-8669) on the Single Dose Pharmacokinetics of Midazolam.
Overview
- Phase
- Phase 1
- Intervention
- Midazolam
- Conditions
- Relapsed or Refractory Advanced Cancer
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 16
- Primary Endpoint
- Maximum Concentration (Cmax) of midazolam 2 mg administered alone versus when administered after multiple oral doses of ridaforolimus 40 mg.
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief 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. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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,
Exclusion Criteria
- •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 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.
Arms & Interventions
All Participants
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.
Intervention: Midazolam
All Participants
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.
Intervention: Ridaforolimus
Outcomes
Primary Outcomes
Maximum Concentration (Cmax) 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)
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.
Time Frame: 8 days (Day -2 through Day 5, 24 hrs postdose)
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.
Time Frame: 8 days (Day -2 through Day 5, 24 hrs postdose)
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)