A Multicenter, Randomized, Controlled Trial of SCH 619734 for the Treatment of Chemotherapy-Induced Nausea and Vomiting (Study P04351AM2)(COMPLETED)

A Phase 2, MultiCenter, Randomized, Placebo-Controlled, Double-Blind, Dose Finding Study to Determine the Safety and Efficacy of SCH 619734 for the Treatment of Chemotherapy Induced Nausea and Vomiting (CINV) in Subjects Receiving Highly Emetogenic Chemotherapy (HEC)

This is a Phase 2, randomized, multicenter, parallel-group, double-blind, placebo-controlled study of various doses of SCH 619734 in subjects receiving cisplatin-based chemotherapy. Ondansetron and dexamethasone will be concurrently administered with SCH 619734 before initiation of chemotherapy on Day 1. Subjects will record nausea and vomiting in the SPNV Subject Diary through Day 6. The quality of life assessment as measured by the Functional Living Index-Emesis Questionnaire (FLIE) will be used to measure the effect of chemotherapy-induced nausea and vomiting (CINV) on daily life. Blood samples for SCH 619734 pharmacokinetic assessments will be collected. The study is to be conducted in conformance with Good Clinical Practice.

Study Overview

• Status: Completed
• Conditions: Nausea; Vomiting
• Intervention / Treatment: Drug: SCH 619734 Dose 1; Drug: SCH 619734 Dose 2; Drug: SCH 619734 Dose 3; Drug: SCH 619734 Dose 4; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is 18 years of age or older.
• Subject has never been treated with cisplatin and is to receive first course of cisplatin-based chemotherapy (>=70 mg/m^2).
• Subject has a Karnofsky performance score of >=60.
• Subject has a predicted life expectancy of >=3 months.

• Subject has adequate bone marrow, kidney, and liver function as evidenced by:

  • Absolute neutrophil count >=1,500/mm3 and white blood cell count >=3,000/mm3.
  • Platelet count >=100,000/mm3.
  • Aspartate aminotransferase (AST) <=2.5 x upper limit of normal (ULN) range.
  • Alanine aminotransferase (ALT) <=2.5 x ULN.
  • Bilirubin <=1.5 x ULN, except for subjects with Gilbert's syndrome.
  • Creatinine <=1.5 x ULN.
• Subject is able to read, understand, and complete the questionnaires.

Exclusion Criteria:

• Any current treatment or medical history (eg, subject is mentally incapacitated or has a psychiatric disorder) that, in the opinion of the investigator, would confound the results of the study or pose any unwarranted risk in administering study drug to the subject.
• Subject has contraindication to the administration of cisplatin, ondansetron, or dexamethasone including, but not limited to, a history of hypersensitivity to the drugs or their components, severe renal impairment, severe bone marrow suppression, hearing impairment, or systemic fungal infection.
• Subject is scheduled to receive any other chemotherapeutic agent with an emetogenicity level of 3 or above (Hesketh Scale) from Day -2 through Day 6.
• Subject is scheduled to receive any radiation therapy to the abdomen or pelvis within 5 days prior to and/or during Days 1 through 5 following cisplatin infusion.
• Subject has symptomatic primary or metastatic central nervous system (CNS) disease.
• Subject has ongoing vomiting caused by any etiology or has a history of anticipatory nausea and vomiting.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo x 1 orally approximately 2 hours prior to the administration of the first chemotherapeutic agent on Day 1 of Cycle 1 and on Day 1 of all subsequent cycles (up to five additional cycles)
Experimental: SCH 619734 Dose 1	Drug: SCH 619734 Dose 1; SCH 619734 10 mg (4 capsules) x 1 orally approximately 2 hours prior to the administration of the first chemotherapeutic agent on Day 1 of Cycle 1 and on Day 1 of all subsequent cycles (up to five additional cycles); Other Names: Rolapitant
Experimental: SCH 619734 Dose 2	Drug: SCH 619734 Dose 2; SCH 619734 25 mg (4 capsules) x 1 orally approximately 2 hours prior to the administration of the first chemotherapeutic agent on Day 1 of Cycle 1 and on Day 1 of all subsequent cycles (up to five additional cycles); Other Names: Rolapitant
Experimental: SCH 619734 Dose 3	Drug: SCH 619734 Dose 3; SCH 619734 100 mg (2 capsules) x 1 orally approximately 2 hours prior to the administration of the first chemotherapeutic agent on Day 1 of Cycle 1 and on Day 1 of all subsequent cycles (up to five additional cycles); Other Names: Rolapitant
Experimental: SCH 619734 Dose 4	Drug: SCH 619734 Dose 4; SCH 619734 200 mg (4 capsules) x 1 orally approximately 2 hours prior to the administration of the first chemotherapeutic agent on Day 1 of Cycle 1 and on Day 1 of all subsequent cycles (up to five additional cycles); Other Names: Rolapitant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary efficacy endpoint is the overall complete response rate (no emesis and no use of rescue medication from 0 through 120 hours following initiation of cisplatin-based chemotherapy).	Days 1 through 6.

Secondary Outcome Measures

Outcome Measure	Time Frame
The key secondary efficacy endpoints are the complete response rates for the acute (0 through 24 hours) and delayed (>24 through 120 hours) phases of CINV.	Days 1 through 6.
The key secondary safety endpoints are adverse events, physical examinations, vital signs, electrocardiograms, and safety laboratory values.	Throughout the study and up to 30 days after the subject completes or discontinues from the study.

Collaborators and Investigators

• Sponsor: Schering-Plough

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: October 31, 2006
• First Submitted That Met QC Criteria: October 31, 2006
• First Posted (Estimate): November 2, 2006

Study Record Updates

• Last Update Posted (Estimate): October 23, 2009
• Last Update Submitted That Met QC Criteria: October 22, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurokinin-1 Receptor Antagonists; Rolapitant
• Other Study ID Numbers: P04351; Study ID: 3283299