Phase 2 Study of Efficacy, Tolerability, and Safety of Intranasal Granisetron for Chemo-Induced Nausea and Vomiting

A Randomized, Single Administration, Double-blind, Parallel-group Phase 2 Dose Finding Study to Assess the Efficacy, Tolerability, and Safety of TRG (Intranasal Granisetron) in Patients With Chemotherapy-induced Nausea and Vomiting (CINV) Associated With the Administration of Highly Emetogenic Chemotherapy

Brief Summary: A randomized, single administration, double-blind, parallel- group Phase 2 dose finding study to assess the efficacy, tolerability, and safety of TRG in patients with chemotherapy-induced nausea and vomiting (CINV) associated with the administration of highly emetogenic chemotherapy.

Primary Objective: To select a dose for Phase 3 by assessing the efficacy, safety, and tolerability of 3 doses of TRG in patients with CINV associated with the administration of highly emetogenic chemotherapy.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-Induced Nausea and Vomiting
• Intervention / Treatment: Drug: Intranasal granisetron

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • The study is managed by Kendle International, in Wilmington, North Carolina, United States, 28405
      • The study is conducted at 14 Centers, in 14 cities accross the United States

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:

• Patients with histologically and/or cytologically confirmed cancer
• ECOG performance status of 0, 1, or 2
• Patients with life expectancy of at least 3 months
• Patients who are chemotherapy naïve
• Patients who will be receiving the first cycle of a highly emetogenic regimen according to the MASCC criteria or the Hesketh criteria
• Patients with adequate metabolic or hematologic values for chemotherapy
• Patients with intact nasal mucosa
• Non child-bearing potential patients
• Patients able to read and write at a competent level, and capable of giving legal consent
• Patients who have provided written informed consent

Exclusion Criteria:

• Patients who do not receive a chemotherapy regimen which is a highly emetogenic chemotherapy regimen according to the MASCC or the Hesketh criteria
• Patients with nasal cancers, pharyngeal cancers, maxillary sinus cancers, or ethmoid sinus cancers
• Patients with nasal ulcers, septal perforation, or other nasal conditions that may interfere with IN administration
• Patients with any episode of retching, vomiting, or uncontrolled nausea within 48 hours before dosing with TRG and/or administration of chemotherapy
• Patients who have received radiation therapy in the 14 days before dosing with TRG, or for whom radiation therapy is scheduled during the 7 days after a TRG dose
• Patients who have received any investigational product within 30 days prior to study entry
• Patients who have received any drug or who were scheduled to receive any drug with antiemetic efficacy within 24 hours of the start of treatment
• Patients who have an allergy or hypersensitivity to granisetron or other selective 5hydroxytryptamine3(5-HT3) receptor antagonists
• Patients with ECOG performance status of 3 or 4
• Patients who have or have a history of brain tumors, head cancers, or neck cancers
• Patients who have a psychological problem that, in the Investigator's opinion, is severe enough to interfere with study eligibility or with interpretation of study results
• Patients who are pregnant (urine test) or breastfeeding
• Patients who have received prior cytotoxic chemotherapy given for the treatment of cancer
• Patients scheduled to receive multiple day chemotherapy
• Patients with clinically relevant abnormal laboratory values at the discretion of the Investigator
• Patients with clinically relevant hepatic, renal, infectious, neurological, or psychiatric disorders, or any other major systemic illness at the discretion of the Investigator
• Patients with any prevalence or cause of nausea and vomiting other than chemotherapy
• Patients using systemic steroids for any indication, or patients using steroids other than dexamethasone for prevention of chemotherapy-induced nausea and vomiting, or patients using dexamethasone for chemotherapy-induced nausea and vomiting at doses other than recommended in the MASCC antiemetic guidelines
• Patients with a QT interval greater than 500 ms or with acute ischemic changes or cardiac abnormality predisposing to arrhythmia on screening electrocardiogram (ECG) or by history
• Patients with a history of drug and/or alcohol abuse.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5 mg of TRG (intranasal granisetron); 0.5 mg dose, intranasal powder, single spray, administered once	Drug: Intranasal granisetron; 0.5 mg, 1.0 mg or 2.0 mg dose of TRG prior to the administration of a highly-emetogenic chemotherapy regimen; Other Names: TRG
Experimental: 1.0 mg of TRG (intranasal granisetron); 1.0 mg dose, intranasal powder, songle spray, administered once	Drug: Intranasal granisetron; 0.5 mg, 1.0 mg or 2.0 mg dose of TRG prior to the administration of a highly-emetogenic chemotherapy regimen; Other Names: TRG
Experimental: 2.0 mg of TRG (intranasal granisetron); 2.0 mg dose, intranasal powder, single spray, administered once	Drug: Intranasal granisetron; 0.5 mg, 1.0 mg or 2.0 mg dose of TRG prior to the administration of a highly-emetogenic chemotherapy regimen; Other Names: TRG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Complete Control	Complete Control is defined as no emetic episodes, no use of rescue medications, and no more than mild nausea as defined by a categorial scale.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Complete Response	Complete Response is defined as no emetic episodes and no use of rescue medications	24 hours
Percentage of Patients With Total Response	Total Response is defined as no nausea, no emetic episodes, and no use of rescue medications	24 hours
Percentage of Patients With Major Control of Emesis	Major Control of emesis = 2 emetic episodes	24 hrs
Percentage of Patients With Minor Control of Emesis	Minor Control of emesis: 3-5 emetic episodes	24 hrs
Percentage of Patients With Failure	Failure: > 5 emetic episodes	24 hrs
Percentage of Patients Using Rescue Medications		24 hours
Time to First Emetic Episode		24 hours
Time to First Rescue Medication		24 hours
Time to Treatment Failure	Time to treatment failure is based on time to first emetic episode or time to rescue medication, whichever occurs first	24 hours
Number of Emetic Episodes		24 hours
Severity of Nausea Measured by a 4 Categorical Scale	4 categorical scale: none, mild (did not interfere with normal daily life), moderate (interfered with normal daily life), and severe (bedridden due to nausea/ required the patient to be bedridden)	24 hours
Patient Global Satisfaction With Antiemetic Therapy Measured by a VAS	VAS (visual analog scale) 0: not at all satisfied, 100: totally satisfied	24 hours

Collaborators and Investigators

• Sponsor: Shin Nippon Biomedical Laboratories, Ltd.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: November 5, 2008
• First Submitted That Met QC Criteria: November 6, 2008
• First Posted (Estimate): November 7, 2008

Study Record Updates

• Last Update Posted (Estimate): July 12, 2011
• Last Update Submitted That Met QC Criteria: July 5, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Highly emetogenic chemotherapy induced nausea and vomiting
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Serotonin Agents; Serotonin Antagonists; Granisetron
• Other Study ID Numbers: TRG-002