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

NCT01071304 | Completed Phase 1

• 2 other identifiers: 8669-0442010_511
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Relapsed or Refractory Advanced Cancer

Keywords

Relapsed or refractory advanced cancer, metastatic cancer, locally advanced cancer

Outcome Measures

Primary Outcomes (4)

• 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.

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

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

  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.

  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.

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

Study Arms (1)

All Participants

EXPERIMENTAL

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.

Drug: Midazolam; Drug: Ridaforolimus

Interventions

Midazolam DRUG

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

All Participants

Ridaforolimus DRUG

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

All Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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-

You may not qualify if:

• \- 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.
• \- 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 24827931 RESULT

MeSH Terms

Conditions

Recurrence; Neoplasm Metastasis

Interventions

Midazolam; ridaforolimus

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Neoplasms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2010
• First Posted: February 19, 2010
• Study Start: March 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: February 1, 2012
• Last Updated: April 10, 2015

Record last verified: 2015-04