Buccal Film Versus IV Injection Palonosetron for Moderately Emetogenic Chemotherapy Induced Nausea and Vomiting

Study Overview
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Brief Summary
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Phase 2 study to compare efficacy, safety and PK of palonosetron, a long acting 5-HT3 receptor antagonist, by buccal film delivery compared to iv injection for chemotherapy induced nausea or vomiting (CINV). Subjects receive a single dose of palonosetron prior to moderately emetogenic chemotherapy.

Detailed Description
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This is a Phase 2 study to compare efficacy, safety and PK of palonosetron, a long acting 5-HT3 receptor antagonist, by buccal film compared to iv injection for moderately emetogenic chemotherapy-induced nausea or vomiting (CINV) in cancer patients. Subjects are randomized into three treatment groups, two with the experimental study drug palonosetron in buccal film at one of two different doses or the control treatment using Palonosetron hydrochloride iv injection. Palonosetron PK will be assessed in a subgroup of each treatment group.

Official Title
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A Randomized, Dose-ranging, Open-label, Parallel Group Study to Assess the Efficacy, Safety and Pharmacokinetics of Palonosetron HCl Buccal Film Versus IV Palonosetron 0.25 mg (ALOXI®) for the Prevention of Chemotherapy-induced Nausea and

Conditions
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Nausea With Vomiting Chemotherapy-Induced

Intervention / Treatment
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* Drug: Palonosetron Hydrochloride Buccal Film 0.25 Mg
* Drug: Palonosetron Hydrochloride Buccal Film 0.5 Mg
* Drug: Palonosetron Hydrochloride, 0.25 Mg/5 mL Intravenous Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With histologically or cytologically confirmed malignant disease; Karnofsky index ≥ 50; Be scheduled to receive the first course of MEC to be administered on Day 1 Using reliable contraceptive measures; negative serum pregnancy test (if potentially child bearing) Be able to read, understand, and follow the study procedures and able to complete patient diary autonomously. Exclusion Criteria: Expect to be non-compliant with the study procedures; Received investigational drugs within 30 days before the start of study treatment or scheduled to receive a highly or moderately emetogenic chemotherapeutic agent during Day 2 to 6 of the study; Has any condition that could have been associated with a risk of emesis near or at the time of study drug administration; Have a clinically unstable seizure disorder with seizure activity requiring anticonvulsant medication; Experienced any vomiting, retching, or National Cancer Institute (NCI) Common Toxicity Criteria grade 2 or 3 or nausea within 24 hours preceding chemotherapy; Have ongoing nausea or vomiting from any organic etiology; Have severe renal or hepatic impairment; Have positive serology test results; Have a known contraindication to 5-HT3 receptor antagonists; Treated with commercially available or investigative palonosetron formulation within 2 weeks prior to start of study treatment; Allergic to palonosetron or any other 5-HT3 antagonist; Currently a user of any recreational or illicit drugs (including marijuana) or has current evidence of drug or alcohol abuse or dependence as determined by the investigator; Will be receiving stem cell rescue therapy in conjunction with study related course of emetogenic chemotherapy; Received or will receive total body irradiation or radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the diary reporting period. Had non-chronic benzodiazepine, opioid or opioid like (e.g., tramadol hydrochloride) therapy initiated within 48 hours prior to study drug administration or is expected to receive within 120 hours following initiation of chemotherapy, except for single daily doses of midazolam, temazepam or triazolam. Started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is expected to receive a corticosteroid as part of chemotherapy regimen.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A (Buccal 0.25 Mg)<br>Palonosetron HCl Buccal Film 0.25 Mg and oral dexamethasone 12 Mg, both administered on Day 1, and dexamethasone 8 Mg PO on days 2 and 3 | Drug: Palonosetron Hydrochloride Buccal Film 0.25 Mg<br>* Dose equal to the iv control<br>* Other names: Buccal Film Low Dose;|
| Experimental: B (Buccal 0.5 Mg)<br>Palonosetron HCl Buccal Film 0.5 Mg and oral dexamethasone 12 Mg, both administered on Day 1, and dexamethasone 8 Mg PO on days 2 and 3 | Drug: Palonosetron Hydrochloride Buccal Film 0.5 Mg<br>* Dose twice that of iv control<br>* Other names: Buccal Film High dose;|
| Active Comparator: C (IV Injection 0.25 Mg)<br>IV palonosetron 0.25 Mg (ALOXI®) and oral dexamethasone 12 Mg, both administered on Day 1, and dexamethasone 8 Mg PO on days 2 and 3 | Drug: Palonosetron Hydrochloride, 0.25 Mg/5 mL Intravenous Solution<br>* iv control<br>* Other names: Control Standard Treatment (Aloxi);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete acute response | no emetic episode and no rescue medication | during the first 24 hours after chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete delayed response | no emetic episode and no rescue medication | 24-120 hours post chemotherapy | 
| Complete response | no emetic episode and no rescue medication | up to 120 hours post chemotherapy | 
| No nausea | visual analog scale (0-100 mm, 0=no, 100=severe) < 5 mm | up to 120 hours post chemotherapy | 
| No significant nausea | visual analog scale (0-100 mm, 0=no, 100=severe) < 25 mm | up to 120 hours post chemotherapy | 
| Complete protection | no emesis, no rescue therapy, no significant nausea (questionnaire) | up to 120 hours post chemotherapy | 
| Number of emetic episodes | Number of emetic episodes | up to 120 hours post chemotherapy | 
| Time to rescue medication | Time to rescue medication | up to 120 hours post chemotherapy | 
| Time to treatment failure | time to first emetic episode or administration of rescue therapy, whichever occurred first | up to 120 hours post chemotherapy | 
| Severity of nausea | Rhodes Index of Nausea, Vomiting and Retching (0-4, 0=no nausea, 4=severe nausea) | up to 120 hours post chemotherapy | 
| Subject global satisfaction with therapy | visual analog scale (0-100mm, 0=not at all satisfied, 100=totally satisfied) | up to 120 hours post chemotherapy | 
| Quality of life questionnaire | Functional Living Index-Emesis | up to 120 hours post chemotherapy |